Stocrin
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ANNEX I

SUMMARY OF PRODUCT CHARACTERISTICS

 



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1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 30 mg/ml oral solution

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml contains 30 mg of efavirenz.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Oral solution

Colourless to slightly yellow clear liquid.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

STOCRIN oral solution is indicated in antiviral combination treatment of human immunodeficiency 
virus-1 (HIV-1) infected adults, adolescents and children 3 years of age and older, who are unable to 
swallow the film-coated tablets.

STOCRIN has not been adequately studied in patients with advanced HIV disease, namely in patients 
with CD4 counts < 50 cells/mm3, or after failure of protease inhibitor (PI) containing regimens. 
Although cross-resistance of efavirenz with PIs has not been documented, there are at present 
insufficient data on the efficacy of subsequent use of PI based combination therapy after failure of 
regimens containing STOCRIN.

For a summary of clinical and pharmacodynamic information, see section 5.1.

4.2 Posology and method of administration

Therapy should be initiated by a physician experienced in the management of HIV infection.

Posology

Efavirenz must be given in combination with other antiretroviral medicines (see section 4.5).

Efavirenz oral solution may be taken with or without food (see section 5.2).

In order to improve the tolerability of nervous system adverse reactions, bedtime dosing is 
recommended during the first two to four weeks of therapy and in patients who continue to experience 
these symptoms (see section 4.8).

Adults
The recommended dose of efavirenz in combination with nucleoside analogue reverse transcriptase 
inhibitors (NRTIs) with or without a PI (see section 4.5) is 24 ml orally, once daily.

Dose adjustment
If efavirenz is coadministered with voriconazole, the voriconazole maintenance dose must be 
increased to 400 mg every 12 hours and the efavirenz dose must be reduced by 50 %, i.e., to 300 mg 

 



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once daily. When treatment with voriconazole is stopped, the initial dose of efavirenz should be 
restored (see section 4.5).

If efavirenz is coadministered with rifampicin to patients weighing 50 kg or more, an increase in the 
dose of efavirenz to 800 mg/day may be considered (see section 4.5).

Children and adolescents (3 to 17 years)
The recommended dose of efavirenz oral solution in combination with a PI and/or NRTIs for patients 
between 3 and 17 years of age is described in Table 1. Efavirenz film-coated tablets must only be 
administered to children who are able to reliably swallow tablets.

Table 1
Paediatric dose to be administered once daily

Body Weight Efavirenz oral solution (30 mg/ml)
kg Dose (ml)

Children 3 - < 5 years Adults and children 
aged 5 years or more

13 to < 15 12 9
15 to < 20 13 10
20 to < 25 15 12

25 to < 32.5 17 15
32.5 to < 40 - 17

 40 - 24

Special populations

Renal impairment
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1 % of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.4).

Hepatic impairment
Patients with mild liver disease may be treated with their normally recommended dose of efavirenz. 
Patients should be monitored carefully for dose-related adverse reactions, especially nervous system 
symptoms (see sections 4.3 and 4.4).

Paediatric population
The safety and efficacy of efavirenz in children below the age of 3 years or weighing less than 13 kg 
have not yet been established. Currently available data are described in sections 4.8, 5.1 and 5.2, but 
no recommendation on a posology can be made.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with severe hepatic impairment (Child Pugh Class C) (see section 5.2).

Co-administration with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, 
or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) 
because competition for CYP3A4 by efavirenz could result in inhibition of metabolism and create the 
potential for serious and/or life-threatening adverse reactions [for example, cardiac arrhythmias, 
prolonged sedation or respiratory depression] (see section 4.5).

Herbal preparations containing St. John’s wort (Hypericum perforatum) due to the risk of decreased 
plasma concentrations and reduced clinical effects of efavirenz (see section 4.5).

 



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Patients with:
-         a family history of sudden death or of congenital prolongation of the QTc interval on 

electrocardiograms, or with any other clinical condition known to prolong the QTc interval.
-         a history of symptomatic cardiac arrythmias or with clinically relevant bradycardia or with 

congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
-         severe disturbances of electrolyte balance e.g. hypokalaemia or hypomagnesaemia.

Patients taking drugs that are known to prolong the QTc interval (proarrhythmic). 
These drugs include:
- antiarrhythmics of classes IA and III,
- neuroleptics, antidepressive agents,
- certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, 

imidazole and triazole antifungal agents,
- certain non-sedating antihistamines (terfenadine, astemizole),
- cisapride,
- flecainide,
- certain antimalarials,
- methadone.

Co-administration with elbasvir/grazoprevir due to the expected significant decreases in elbasvir and 
grazoprevir plasma concentrations (see section 4.5). This effect is due to an induction of CYP3A4 or 
P-gp by efavirenz and is expected to result in the loss of virologic response of elbasvir/grazoprevir.

4.4 Special warnings and precautions for use

Efavirenz must not be used as a single agent to treat HIV or added on as a sole agent to a failing 
regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy. The choice 
of new antiretroviral agent(s) to be used in combination with efavirenz should take into consideration 
the potential for viral cross-resistance (see section 5.1).

Co-administration of efavirenz with a fixed combination tablet containing efavirenz, emtricitabine, 
and tenofovir disoproxil, is not recommended unless needed for dose adjustment (for example, with 
rifampicin).

Co-administration of glecaprevir/pibrentasvir with efavirenz may significantly decrease plasma
concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect. 
Co-administration of glecaprevir/pibrentasvir with efavirenz is not recommended (see section 4.5).

Concomitant use of Ginkgo biloba extracts is not recommended (see section 4.5).

When prescribing medicinal products concomitantly with efavirenz, physicians should refer to the 
corresponding Summary of Product Characteristics.

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission 
should be taken in accordance with national guidelines.

If any antiretroviral medicinal product in a combination regimen is interrupted because of suspected 
intolerance, serious consideration should be given to simultaneous discontinuation of all antiretroviral 
medicinal products. The antiretroviral medicinal products should be restarted at the same time upon 
resolution of the intolerance symptoms. Intermittent monotherapy and sequential reintroduction of 
antiretroviral agents is not advisable because of the increased potential for selection of resistant virus.

 



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Rash

Mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with 
continued therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and 
hasten the resolution of rash. Severe rash associated with blistering, moist desquamation or ulceration 
has been reported in less than 1 % of patients treated with efavirenz. The incidence of erythema 
multiforme or Stevens-Johnson syndrome was approximately 0.1 %. Efavirenz must be discontinued 
in patients developing severe rash associated with blistering, desquamation, mucosal involvement or 
fever. If therapy with efavirenz is discontinued, consideration should also be given to interrupting 
therapy with other antiretroviral agents to avoid development of resistant virus (see section 4.8).

Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class
is limited (see section 4.8). Efavirenz is not recommended for patients who have had a life-threatening 
cutaneous reaction (e.g., Stevens-Johnson syndrome) while taking another NNRTI.

Psychiatric symptoms

Psychiatric adverse reactions have been reported in patients treated with efavirenz. Patients with a 
prior history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse 
reactions. In particular, severe depression was more common in those with a history of depression.
There have also been post-marketing reports of severe depression, death by suicide, delusions,
psychosis-like behaviour and catatonia. Patients should be advised that if they experience symptoms 
such as severe depression, psychosis or suicidal ideation, they should contact their doctor immediately 
to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to 
determine whether the risks of continued therapy outweigh the benefits (see section 4.8).

Nervous system symptoms

Symptoms including, but not limited to, dizziness, insomnia, somnolence, impaired concentration and 
abnormal dreaming are frequently reported adverse reactions in patients receiving efavirenz 600 mg 
daily in clinical studies (see section 4.8). Nervous system symptoms usually begin during the first one 
or two days of therapy and generally resolve after the first 2 - 4 weeks. Patients should be informed 
that if they do occur, these common symptoms are likely to improve with continued therapy and are 
not predictive of subsequent onset of any of the less frequent psychiatric symptoms.

Seizures

Convulsions have been observed in patients receiving efavirenz, generally in the presence of known 
medical history of seizures. Patients who are receiving concomitant anticonvulsant medicinal products 
primarily metabolised by the liver, such as phenytoin, carbamazepine and phenobarbital, may require 
periodic monitoring of plasma levels. In a drug interaction study, carbamazepine plasma 
concentrations were decreased when carbamazepine was co-administered with efavirenz (see 
section 4.5). Caution must be taken in any patient with a history of seizures.

Hepatic events

A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic 
disease or other identifiable risk factors (see section 4.8). Liver enzyme monitoring should be 
considered for patients without pre-existing hepatic dysfunction or other risk factors.

QTc Prolongation

QTc prolongation has been observed with the use of efavirenz (see sections 4.5 and 5.1). 

Consider alternatives to efavirenz for co-administration with a drug with a known risk of Torsade de 
Pointes or when to be administered to patients at higher risk of Torsade de Pointes.

 



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Immune Reactivation Syndrome

In HIV infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any 
inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune 
disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the
setting of immune reactivation; however, the reported time to onset is more variable and these events 
can occur many months after initiation of treatment.

Weight and metabolic parameters

An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment. For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.

Osteonecrosis

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination 
antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience 
joint aches and pain, joint stiffness or difficulty in movement.

Special populations

Liver disease
Efavirenz is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 5.2) and 
not recommended in patients with moderate hepatic impairment because of insufficient data to 
determine whether dose adjustment is necessary. Because of the extensive cytochrome P450-mediated 
metabolism of efavirenz and limited clinical experience in patients with chronic liver disease, caution 
must be exercised in administering efavirenz to patients with mild hepatic impairment. Patients should 
be monitored carefully for dose-related adverse reactions, especially nervous system symptoms. 
Laboratory tests should be performed to evaluate their liver disease at periodic intervals 
(see section 4.2).

The safety and efficacy of efavirenz has not been established in patients with significant underlying 
liver disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral 
therapy are at increased risk for severe and potentially fatal hepatic adverse reactions. Patients with 
pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver 
function abnormalities during combination antiretroviral therapy and should be monitored according 
to standard practice. If there is evidence of worsening liver disease or persistent elevations of serum 
transaminases to greater than 5 times the upper limit of the normal range, the benefit of continued 
therapy with efavirenz needs to be weighed against the potential risks of significant liver toxicity. In 
such patients, interruption or discontinuation of treatment must be considered (see section 4.8).

In patients treated with other medicinal products associated with liver toxicity, monitoring of liver 
enzymes is also recommended. In case of concomitant antiviral therapy for hepatitis B or C, please 
refer also to the relevant product information for these medicinal products.

 



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Renal insufficiency
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1 % of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.2). There is no experience in 
patients with severe renal failure and close safety monitoring is recommended in this population.

Elderly patients
Insufficient numbers of older patients have been evaluated in clinical studies to determine whether 
they respond differently than younger patients.

Paediatric population
Efavirenz has not been evaluated in children below 3 years of age or who weigh less than 13 kg. 
Evidence exists indicating that efavirenz may have altered pharmacokinetics in very young children. 
For this reason, efavirenz oral solution should not be given to children less than 3 years of age.

Rash was reported in 26 of 57 children (46 %) treated with efavirenz during a 48-week period and was 
severe in three patients. Prophylaxis with appropriate antihistamines prior to initiating therapy with 
efavirenz in children may be considered.

4.5 Interaction with other medicinal products and other forms of interaction

Efavirenz is an in vivo inducer of CYP3A4, CYP2B6 and UGT1A1. Compounds that are substrates of 
these enzymes may have decreased plasma concentrations when co-administered with efavirenz. In 
vitro efavirenz is also an inhibitor of CYP3A4. Theoretically, efavirenz may therefore initially 
increase the exposure to CYP3A4 substrates and caution is warranted for CYP3A4 substrates with 
narrow therapeutic index (see section 4.3). Efavirenz may be an inducer of CYP2C19 and CYP2C9; 
however inhibition has also been observed in vitro and the net effect of co-administration with 
substrates of these enzymes is not clear (see section 5.2).

Efavirenz exposure may be increased when given with medicinal products (for example, ritonavir) or 
food (for example, grapefruit juice), which inhibit CYP3A4 or CYP2B6 activity. Compounds or 
herbal preparations (for example Ginkgo biloba extracts and St. John’s wort) which induce these 
enzymes may give rise to decreased plasma concentrations of efavirenz. Concomitant use of St. John’s 
wort is contraindicated (see section 4.3). Concomitant use of Ginkgo biloba extracts is not 
recommended (see section 4.4).

QT Prolonging Drugs

Efavirenz is contraindicated with concomitant use of drugs (they may cause prolonged QTc interval 
and Torsade de Pointes) such as: antiarrhythmics of classes IA and III, neuroleptics and antidepressant 
agents, certain antibiotics including some agents of the following classes: macrolides, 
fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics 
(terfenadine, astemizole), cisapride, flecainide, certain antimalarials and methadone (see section 4.3).

Paediatric population

Interaction studies have only been performed in adults.

Contraindications of concomitant use

Efavirenz must not be administered concurrently with terfenadine, astemizole, cisapride, midazolam, 
triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, 
ergonovine, and methylergonovine) since inhibition of their metabolism may lead to serious, 
life-threatening events (see section 4.3).

Efavirenz must not be administered with elbasvir/grazoprevir due to the expected significant decreases 
in elbasvir and grazoprevir plasma concentrations caused by induction of drug metabolising enzymes 

 



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and/or transport proteins and which are expected to result in the loss of virologic response of 
elbasvir/grazoprevir (see section 4.5).

St. John’s wort (Hypericum perforatum)

Co-administration of efavirenz and St. John’s wort or herbal preparations containing St. John’s wort is 
contraindicated. Plasma levels of efavirenz can be reduced by concomitant use of St. John's wort due 
to induction of drug metabolising enzymes and/or transport proteins by St. John's wort. If a patient is 
already taking St. John’s wort, stop St. John’s wort, check viral levels and if possible efavirenz levels. 
Efavirenz levels may increase on stopping St. John’s wort and the dose of efavirenz may need 
adjusting. The inducing effect of St. John’s wort may persist for at least 2 weeks after cessation of 
treatment (see section 4.3).

Other interactions
Interactions between efavirenz and protease inhibitors, antiretroviral agents other than protease 
inhibitors and other non-antiretroviral medicinal products are listed in Table 2 below (increase is 
indicated as “↑”, decrease as “↓”, no change as “↔”, and once every 8 or 12 hours as “q8h” or 
“q12h”). If available, 90 % or 95 % confidence intervals are shown in parentheses. Studies were 
conducted in healthy subjects unless otherwise noted. 

Table 2: Interactions between efavirenz and other medicinal products in adults

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

ANTI-INFECTIVES
HIV antivirals
Protease inhibitors (PI)
Atazanavir/ ritonavir/Efavirenz
(400 mg once daily/100 mg once 
daily/600 mg once daily, all 
administered with food)

Atazanavir (pm):
AUC: ↔* (↓ 9 to ↑ 10)
Cmax: ↑ 17 %* (↑ 8 to ↑ 27)
Cmin: ↓ 42 %* (↓ 31 to ↓ 51)

Co-administration of efavirenz 
with atazanavir/ritonavir is not 
recommended. If the 
co-administration of atazanavir 
with an NNRTI is required, an 
increase in the dose of both 
atazanavir and ritonavir to 400 mg 
and 200 mg, respectively, in 
combination with efavirenz could 
be considered with close clinical 
monitoring.

Atazanavir/ritonavir/Efavirenz
(400 mg once daily/200 mg once 
daily/600 mg once daily, all 
administered with food)

Atazanavir (pm):
AUC: ↔*/** (↓ 10 to ↑ 26)
Cmax: ↔*/** (↓ 5 to ↑ 26)
Cmin: ↑ 12 %*/** (↓ 16 to ↑ 49)
(CYP3A4 induction).
* When compared to atazanavir 
300 mg/ritonavir 100 mg once 
daily in the evening without 
efavirenz. This decrease in 
atazanavir Cmin might negatively 
impact the efficacy of atazanavir.
** based on historical comparison

Darunavir/ritonavir/Efavirenz
(300 mg twice daily*/100 mg twice 
daily/600 mg once daily)

*lower than recommended doses, 
similar findings are expected with 
recommended doses.

Darunavir:
AUC : ↓ 13 %
Cmin : ↓ 31 %
Cmax: ↓ 15%
(CYP3A4 induction)
Efavirenz:
AUC : ↑ 21 %
Cmin: ↑ 17 %
Cmax: ↑ 15%
(CYP3A4 inhibition)

Efavirenz in combination with 
darunavir/ritonavir 800/100 mg 
once daily may result in 
suboptimal darunavir Cmin. If 
efavirenz is to be used in 
combination with 
darunavir/ritonavir, the 

darunavir/ritonavir 600/100 mg 
twice daily regimen should be 
used. This combination should be 
used with caution.
See also ritonavir row below.

 



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Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Fosamprenavir/ritonavir/Efavirenz
(700 mg twice daily/100 mg twice 
daily/600 mg once daily)

No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for any of these medicinal 
products. 
See also ritonavir row below.

Fosamprenavir/Nelfinavir/Efavirenz Interaction not studied No dose adjustment is necessary 
for any of these medicinal 
products.

Fosamprenavir/Saquinavir/Efavirenz Interaction not studied Not recommended, as the 
exposure to both PIs is expected to 
be significantly decreased.

Indinavir/Efavirenz
(800 mg q8h/200 mg once daily)

Indinavir:
AUC: ↓ 31 % (↓ 8 to ↓ 47)
Cmin: ↓ 40 %
A similar reduction in indinavir 
exposures was observed when 
indinavir 1,000 mg q8h was given 
with efavirenz 600 mg daily.
(CYP3A4 induction)
Efavirenz:
No clinically significant 
pharmacokinetic interaction

While the clinical significance of 
decreased indinavir concentrations 
has not been established, the 
magnitude of the observed 
pharmacokinetic interaction 
should be taken into consideration 
when choosing a regimen 
containing both efavirenz and 
indinavir.

No dose adjustment is necessary 
for efavirenz when given with 
indinavir or indinavir/ritonavir.

See also ritonavir row below.

Indinavir/ritonavir/Efavirenz
(800 mg twice daily/100 mg twice 
daily/600 mg once daily)

Indinavir:
AUC: ↓ 25 % (↓ 16 to ↓ 32) b

Cmax: ↓ 17 % (↓ 6 to ↓ 26)
b

Cmin: ↓ 50 % (↓ 40 to ↓ 59)
b

Efavirenz:
No clinically significant 
pharmacokinetic interaction
The geometric mean Cmin for 
indinavir (0.33 mg/l) when given 
with ritonavir and efavirenz was 
higher than the mean historical 
Cmin (0.15 mg/l) when indinavir 
was given alone at 800 mg q8h. 
In HIV-1 infected patients 
(n = 6), the pharmacokinetics of 
indinavir and efavirenz were 
generally comparable to these 
uninfected volunteer data.

Lopinavir/ritonavir soft capsules or 
oral solution/Efavirenz

Lopinavir/ritonavir tablets/ Efavirenz

Substantial decrease in lopinavir 
exposure.

With efavirenz, an increase of the 
lopinavir/ritonavir soft capsule or 
oral solution doses by 33 % should 
be considered (4 capsules/~6.5 ml 
twice daily instead of 
3 capsules/5 ml twice daily). 
Caution is warranted since this 
dose adjustment might be
insufficient in some patients. The 
dose of lopinavir/ritonavir tablets 
should be increased to 500/125 mg 
twice daily when co-administered
with efavirenz 600 mg once daily.
See also ritonavir row below.

(400/100 mg twice daily/600 mg once 
daily)

Lopinavir concentrations: 
↓ 30-40 %

(500/125 mg twice daily/600 mg once 
daily)

Lopinavir concentrations: similar 
to lopinavir/ritonavir 400/100 mg 
twice daily without efavirenz

 



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Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Nelfinavir/Efavirenz
(750 mg q8h/600 mg once daily)

Nelfinavir:
AUC: ↑ 20 % (↑ 8 to ↑ 34)
Cmax: ↑ 21 % (↑ 10 to ↑ 33)
The combination was generally 
well tolerated.

No dose adjustment is necessary 
for either medicinal product.

Ritonavir/Efavirenz
(500 mg twice daily/600 mg once 
daily)

Ritonavir:
Morning AUC: ↑ 18 % (↑ 6 to 
↑ 33)
Evening AUC: ↔
Morning Cmax: ↑ 24 % (↑ 12 to 
↑ 38)
Evening Cmax: ↔
Morning Cmin: ↑ 42 % (↑ 9 to 
↑ 86)b 

Evening Cmin: ↑ 24 % (↑ 3 to 
↑ 50)b

Efavirenz:
AUC: ↑ 21 % (↑ 10 to ↑ 34)
Cmax: ↑ 14 % (↑ 4 to ↑ 26)
Cmin: ↑ 25 % (↑ 7 to ↑ 46)

b

(inhibition of CYP-mediated 
oxidative metabolism)
When efavirenz was given with 
ritonavir 500 mg or 600 mg twice 
daily, the combination was not 
well tolerated (for example, 
dizziness, nausea, paraesthesia 
and elevated liver enzymes 
occurred). Sufficient data on the 
tolerability of efavirenz with 
low-dose ritonavir (100 mg, once 
or twice daily) are not available. 

When using efavirenz with 
low-dose ritonavir, the possibility 
of an increase in the incidence of 
efavirenz-associated adverse 
events should be considered, due 
to possible pharmacodynamic 
interaction.

Saquinavir/ritonavir/Efavirenz Interaction not studied. No data are available to make a 
dose recommendation. See also 
ritonavir row above. Use of 
efavirenz in combination with 
saquinavir as the sole protease 
inhibitor is not recommended.

CCR5 antagonist
Maraviroc/Efavirenz
(100 mg twice daily/600 mg once 
daily)

Maraviroc:
AUC12: ↓ 45 % (↓ 38 to ↓ 51)
Cmax: ↓ 51 % (↓ 37 to ↓ 62)
Efavirenz concentrations not 
measured, no effect is expected.

Refer to the Summary of Product 
Characteristics for the medicinal 
product containing maraviroc.

Integrase strand transfer inhibitor
Raltegravir/Efavirenz
(400 mg single dose/ - )

Raltegravir:
AUC: ↓ 36 %
C12: ↓ 21 %
Cmax: ↓ 36 %
(UGT1A1 induction)

No dose adjustment is necessary 
for raltegravir.

 



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Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

NRTIs and NNRTIs
NRTIs/Efavirenz Specific interaction studies have 

not been performed with 
efavirenz and NRTIs other than 
lamivudine, zidovudine, and 
tenofovir disoproxil. Clinically 
significant interactions are not 
expected since the NRTIs are 
metabolised via a different route 
than efavirenz and would be 
unlikely to compete for the same 
metabolic enzymes and 
elimination pathways.

No dose adjustment is necessary 
for either medicinal product.

NNRTIs/Efavirenz Interaction not studied. Since use of two NNRTIs proved 
not beneficial in terms of efficacy 
and safety, co-administration of 
efavirenz and another NNRTI is 
not recommended.

Hepatitis C antivirals
Boceprevir/Efavirenz
(800 mg 3 times daily/600 mg once 
daily)

Boceprevir:
AUC: ↔ 19%*
Cmax: ↔ 8%

Cmin: ↓ 44%
Efavirenz:
AUC: ↔ 20%
Cmax: ↔ 11%
(CYP3A induction - effect on 
boceprevir)
*0-8 hours
No effect (↔) equals a decrease 
in mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25%

Plasma trough concentrations of 
boceprevir were decreased when 
administered with efavirenz. The 
clinical outcome of this observed 
reduction of boceprevir trough 
concentrations has not been 
directly assessed.

Telaprevir/Efavirenz
(1,125 mg q8h/600 mg once daily)

Telaprevir (relative to 750 mg 
q8h):
AUC: ↓ 18% (↓ 8 to ↓ 27)
Cmax: ↓ 14% (↓ 3 to ↓ 24)

Cmin: ↓ 25% (↓ 14 to ↓ 34)%
Efavirenz:
AUC: ↓ 18% (↓ 10 to ↓ 26)
Cmax: ↓ 24% (↓ 15 to ↓ 32)

Cmin: ↓ 10% (↑ 1 to ↓ 19)%
(CYP3A induction by efavirenz)

If efavirenz and telaprevir are 
co-administered, telaprevir 
1,125 mg every 8 hours should be 
used.

Simeprevir/Efavirenz
(150 mg once daily /600 mg once 
daily)

Simeprevir: 
AUC: ↓ 71% (↓ 67 to ↓ 74)
Cmax: ↓ 51% (↓ 46 to ↓ 56)
Cmin: ↓ 91% (↓ 88 to ↓ 92)
Efavirenz:
AUC: ↔ 
Cmax: ↔
Cmin: ↔
No effect (↔) equals a decrease 
in mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25%
(CYP3A4 enzyme induction)

Concomitant administration of 
simeprevir with efavirenz resulted 
in significantly decreased plasma 
concentrations of simeprevir due 
to CYP3A induction by efavirenz, 
which may result in loss of 
therapeutic effect of simeprevir. 
Co-administration of simeprevir
with efavirenz is not 
recommended.)

 



12

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Elbasvir/grazoprevir Elbasvir:
AUC: ↓54%
Cmax: ↓45%

Grazoprevir:
AUC: ↓83%
Cmax: ↓87%

Concomitant administration of 
STOCRIN with 
elbasvir/grazoprevir is 
contraindicated (see section 4.3) 
because it may lead to loss of 
virologic response to 
elbasvir/grazoprevir. This loss is 
due to significant decreases in 
elbasvir and grazoprevir plasma 
concentrations caused by CYP3A4
or P-gp induction (refer to the 
Summary of Product 
Characteristics for 
elbasvir/grazoprevir for additional
information).

Sofosbuvir/velpatasvir 
sofosbuvir/velpatasvir/voxilaprevir

Sofosbuvir:
Cmax ↑38%

Velpatasvir
AUC ↓53%
Cmax ↓47%
Cmin ↓57%

Expected:
↓ Voxilaprevir

Co-administration of 
efavirenz/emtricitabine/tenofovir 
disoproxil with 
sofosbuvir/velpatasvir has been 
shown to significantly decrease 
plasma concentrations of 
velpatasvir due to CYP3A 
induction by efavirenz, which may 
result in loss of therapeutic effect 
of velpatasvir. Although not 
studied, a similar decrease in 
voxilaprevir exposure is 
anticipated. Co-administration of 
STOCRIN with 
sofosbuvir/velpatasvir or 
sofosbuvir/velpatasvir/voxilaprevir 
is not recommended (refer to the 
Summary of Product 
Characteristics for 
sofosbuvir/velpatasvir and 
sofosbuvir/velpatasvir/voxilaprevir 
for additional information).

Glecaprevir/pibrentasvir ↓glecaprevir
↓pibrentasvir

Concomitant administration of 
glecaprevir/pibrentasvir with 
efavirenz may significantly 
decrease plasma concentrations 
of glecaprevir and pibrentasvir, 
leading to reduced therapeutic 
effect.
Co-administration of
glecaprevir/pibrentasvir with
efavirenz is not recommended. 
Refer to the prescribing 
information for
glecaprevir/pibrentasvir for
more information.

 



13

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Antibiotics
Azithromycin/Efavirenz
(600 mg single dose/400 mg once 
daily)

No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for either medicinal product.

Clarithromycin/Efavirenz
(500 mg q12h/400 mg once daily)

Clarithromycin:
AUC: ↓ 39 % (↓ 30 to ↓ 46)
Cmax: ↓ 26 % (↓ 15 to ↓ 35)
Clarithromycin 
14-hydroxymetabolite:
AUC: ↑ 34 % (↑ 18 to ↑ 53)
Cmax: ↑ 49 % (↑ 32 to ↑ 69)
Efavirenz:
AUC: ↔
Cmax: ↑ 11 % (↑ 3 to ↑ 19)
(CYP3A4 induction)
Rash developed in 46 % of 
uninfected volunteers receiving 
efavirenz and clarithromycin.

The clinical significance of these 
changes in clarithromycin plasma 
levels is not known. Alternatives 
to clarithromycin (e.g. 
azithromycin) may be considered. 
No dose adjustment is necessary 
for efavirenz.  

Other macrolide antibiotics (e.g., 
erythromycin)/Efavirenz

Interaction not studied. No data are available to make a 
dose recommendation.

Antimycobacterials
Rifabutin/Efavirenz
(300 mg once daily/600 mg once 
daily)

Rifabutin:
AUC: ↓ 38 % (↓ 28 to ↓ 47)
Cmax: ↓ 32 % (↓ 15 to ↓ 46)
Cmin: ↓ 45 % (↓ 31 to ↓ 56) 
Efavirenz:
AUC: ↔
Cmax: ↔
Cmin: ↓ 12 % (↓ 24 to ↑ 1) 
(CYP3A4 induction)

The daily dose of rifabutin should 
be increased by 50 % when 
administered with efavirenz. 
Consider doubling the rifabutin 
dose in regimens where rifabutin 
is given 2 or 3 times a week in 
combination with efavirenz. The 
clinical effect of this dose 
adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2).

Rifampicin/Efavirenz
(600 mg once daily/600 mg once 
daily)

Efavirenz:
AUC: ↓ 26 % (↓ 15 to ↓ 36)
Cmax: ↓ 20 % (↓ 11 to ↓ 28)
Cmin: ↓ 32 % (↓ 15 to ↓ 46) 
(CYP3A4 and CYP2B6 
induction)

When taken with rifampicin in 
patients weighing 50 kg or greater, 
increasing efavirenz daily dose to 
800 mg may provide exposure 
similar to a daily dose of 600 mg,
when taken without rifampicin.
The clinical effect of this dose 
adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2). No dose 
adjustment is necessary for 
rifampicin, including 600 mg.

 



14

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Antifungals
Itraconazole/Efavirenz
(200 mg q12h/600 mg once daily)

Itraconazole: 
AUC: ↓ 39 % (↓ 21 to ↓ 53)
Cmax: ↓ 37 % (↓ 20 to ↓ 51)
Cmin: ↓ 44 % (↓ 27 to ↓ 58) 
(decrease in itraconazole 
concentrations: CYP3A4 
induction)
Hydroxyitraconazole:
AUC: ↓ 37 % (↓ 14 to ↓ 55) 
Cmax: ↓ 35 % (↓ 12 to ↓ 52) 
Cmin: ↓ 43 % (↓ 18 to ↓ 60) 
Efavirenz: 
No clinically significant 
pharmacokinetic change.  

Since no dose recommendation for 
itraconazole can be made, 
alternative antifungal treatment 
should be considered.

Posaconazole/Efavirenz
--/400 mg once daily

Posaconazole:
AUC: ↓ 50 % 

Cmax: ↓ 45 %
(UDP-G induction)

Concomitant use of posaconazole 
and efavirenz should be avoided 
unless the benefit to the patient 
outweighs the risk.

Voriconazole/Efavirenz
(200 mg twice daily/400 mg once 
daily)

Voriconazole/Efavirenz
(400 mg twice daily/300 mg once 
daily)

Voriconazole:
AUC: ↓ 77 %
Cmax: ↓ 61 %
Efavirenz:
AUC: ↑ 44 %
Cmax: ↑ 38 %
Voriconazole:
AUC: ↓ 7 % (↓ 23 to ↑ 13) *
Cmax: ↑ 23 % (↓ 1 to ↑ 53) *
Efavirenz:
AUC: ↑ 17 % (↑ 6 to ↑ 29) **
Cmax: ↔**
*compared to 200 mg twice daily 
alone
** compared to 600 mg once 
daily alone
(competitive inhibition of 
oxidative metabolism)

When efavirenz is co-administered 
with voriconazole, the 
voriconazole maintenance dose 
must be increased to 400 mg twice 
daily and the efavirenz dose must 
be reduced by 50 %, i.e., to 
300 mg once daily. When 
treatment with voriconazole is 
stopped, the initial dose of 
efavirenz should be restored.

Fluconazole/Efavirenz
(200 mg once daily/400 mg once 
daily)

No clinically significant 
pharmacokinetic interaction

No dose adjustment is necessary 
for either medicinal product.

Ketoconazole and other imidazole 
antifungals

Interaction not studied No data are available to make a 
dose recommendation.

Antimalarials
Artemether/lumefantrine/
Efavirenz
(20/120 mg tablet, 6 doses of 4 tablets 
each over 3 days/600 mg once daily)

Artemether:
AUC: ↓ 51% 
Cmax: ↓ 21% 
Dihydroartemisinin:
AUC: ↓ 46%
Cmax: ↓ 38% 
Lumefantrine:
AUC: ↓ 21% 
Cmax: ↔
Efavirenz:
AUC: ↓ 17%
Cmax: ↔
(CYP3A4 induction)

Since decreased concentrations of 
artemether, dihydroartemisinin, or 
lumefantrine may result in a 
decrease of antimalarial efficacy, 
caution is recommended when 
efavirenz and 
artemether/lumefantrine tablets are 
coadministered.

 



15

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Atovaquone and proguanil 
hydrochloride/Efavirenz
(250/100 mg single dose/600 mg once 
daily)

Atovaquone:
AUC: ↓ 75% (↓ 62 to ↓ 84)

Cmax: ↓ 44% (↓ 20 to ↓ 61)

Proguanil:
AUC: ↓ 43% (↓ 7 to ↓ 65)
Cmax: ↔

Concomitant administration of 
atovaquone/proguanil with 
efavirenz should be avoided.

ACID REDUCING AGENTS
Aluminium hydroxide-magnesium 
hydroxide-simethicone 
antacid/Efavirenz
(30 mL single dose/400 mg single 
dose)
Famotidine/Efavirenz
(40 mg single dose/400 mg single 
dose)

Neither aluminium/magnesium 
hydroxide antacids nor famotidine 
altered the absorption of 
efavirenz.  

Co-administration of efavirenz 
with medicinal products that alter 
gastric pH would not be expected 
to affect efavirenz absorption.

ANTIANXIETY AGENTS
Lorazepam/Efavirenz
(2 mg single dose/600 mg once daily)

Lorazepam: 
AUC: ↑ 7 % (↑ 1 to ↑ 14)
Cmax: ↑ 16 % (↑ 2 to ↑ 32)
These changes are not considered 
clinically significant.  

No dose adjustment is necessary 
for either medicinal product.

ANTICOAGULANTS
Warfarin/Efavirenz
Acenocoumarol/Efavirenz

Interaction not studied. Plasma 
concentrations and effects of 
warfarin or acenocoumarol are 
potentially increased or decreased 
by efavirenz.

Dose adjustment of warfarin or 
acenocoumarol may be required.

ANTICONVULSANTS
Carbamazepine/Efavirenz
(400 mg once daily/600 mg once 
daily)

Carbamazepine:
AUC: ↓ 27 % (↓ 20 to ↓ 33)
Cmax: ↓ 20 % (↓ 15 to ↓ 24)
Cmin: ↓ 35 % (↓ 24 to ↓ 44)
Efavirenz:
AUC: ↓ 36 % (↓ 32 to ↓ 40)
Cmax: ↓ 21 % (↓ 15 to ↓ 26)
Cmin: ↓ 47 % (↓ 41 to ↓ 53)
(decrease in carbamazepine 
concentrations: CYP3A4 
induction; decrease in efavirenz 
concentrations: CYP3A4 and 
CYP2B6 induction) 
The steady-state AUC, Cmax and 
Cmin of the active carbamazepine 
epoxide metabolite remained 
unchanged. Co-administration of 
higher doses of either efavirenz or 
carbamazepine has not been 
studied.

No dose recommendation can be 
made. An alternative 
anticonvulsant should be 
considered. Carbamazepine 
plasma levels should be monitored 
periodically.

 



16

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Phenytoin, Phenobarbital, and other 
anticonvulsants that are substrates of 
CYP450 isoenzymes

Interaction not studied. There is a 
potential for reduction or increase 
in the plasma concentrations of 
phenytoin, phenobarbital and 
other anticonvulsants that are 
substrates of CYP450 isoenzymes 
when co-administered with 
efavirenz.

When efavirenz is co-administered 
with an anticonvulsant that is a 
substrate of CYP450 isoenzymes, 
periodic monitoring of 
anticonvulsant levels should be 
conducted.

Valproic acid/Efavirenz
(250 mg twice daily/600 mg once 
daily)

No clinically significant effect on 
efavirenz pharmacokinetics. 
Limited data suggest there is no 
clinically significant effect on 
valproic acid pharmacokinetics.

No dose adjustment is necessary 
for efavirenz. Patients should be 
monitored for seizure control.

Vigabatrin/Efavirenz
Gabapentin/Efavirenz

Interaction not studied. Clinically 
significant interactions are not 
expected since vigabatrin and 
gabapentin are exclusively 
eliminated unchanged in the urine 
and are unlikely to compete for 
the same metabolic enzymes and 
elimination pathways as 
efavirenz.

No dose adjustment is necessary 
for any of these medicinal 
products.

ANTIDEPRESSANTS
Selective Serotonin Reuptake Inhibitors (SSRIs)
Sertraline/Efavirenz
(50 mg once daily/600 mg once daily)

Sertraline:
AUC: ↓ 39 % (↓ 27 to ↓ 50) 
Cmax: ↓ 29 % (↓ 15 to ↓ 40) 
Cmin: ↓ 46 % (↓ 31 to ↓ 58)
Efavirenz: 
AUC: ↔
Cmax: ↑ 11 % (↑ 6 to ↑ 16)
Cmin: ↔ 
(CYP3A4 induction)

Sertraline dose increases should be 
guided by clinical response.
No dose adjustment is necessary 
for efavirenz.

Paroxetine/Efavirenz
(20 mg once daily/600 mg once daily)

No clinically significant 
pharmacokinetic interaction

No dose adjustment is necessary 
for either medicinal product.

Fluoxetine/Efavirenz Interaction not studied. Since 
fluoxetine shares a similar 
metabolic profile with paroxetine, 
i.e. a strong CYP2D6 inhibitory 
effect, a similar lack of 
interaction would be expected for 
fluoxetine.

No dose adjustment is necessary 
for either medicinal product.

Norepinephrine and dopamine reuptake inhibitor
Bupropion/Efavirenz
[150 mg single dose (sustained 
release)/600 mg once daily]

Bupropion:

AUC: ↓ 55% (↓ 48 to ↓ 62) 

Cmax: ↓ 34% (↓ 21 to ↓ 47) 
Hydroxybupropion: 
AUC: ↔

Cmax: ↑ 50% (↑ 20 to ↑ 80)
(CYP2B6 induction)

Increases in bupropion dosage 
should be guided by clinical 
response, but the maximum 
recommended dose of bupropion 
should not be exceeded. No dose 
adjustment is necessary for 
efavirenz.

 



17

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

ANTIHISTAMINES
Cetirizine/Efavirenz
(10 mg single dose/600 mg once 
daily)

Cetirizine:
AUC: ↔
Cmax: ↓ 24 % (↓ 18 to ↓ 30)
These changes are not considered 
clinically significant.
Efavirenz: 
No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for either medicinal product.

CARDIOVASCULAR AGENTS
Calcium Channel Blockers  
Diltiazem/Efavirenz
(240 mg once daily/600 mg once 
daily)

Diltiazem:
AUC: ↓ 69 % (↓ 55 to ↓ 79) 
Cmax: ↓ 60 % (↓ 50 to ↓ 68) 
Cmin: ↓ 63 % (↓ 44 to ↓ 75)
Desacetyl diltiazem:
AUC: ↓ 75 % (↓ 59 to ↓ 84) 
Cmax: ↓ 64 % (↓ 57 to ↓ 69) 
Cmin: ↓ 62 % (↓ 44 to ↓ 75)
N-monodesmethyl diltiazem:
AUC: ↓ 37 % (↓ 17 to ↓ 52)
Cmax: ↓ 28 % (↓ 7 to ↓ 44)
Cmin: ↓ 37 % (↓ 17 to ↓ 52)
Efavirenz:
AUC: ↑ 11 % (↑ 5 to ↑ 18)
Cmax: ↑ 16 % (↑ 6 to ↑ 26) 
Cmin: ↑ 13 % (↑ 1 to ↑ 26)
(CYP3A4 induction)
The increase in efavirenz 
pharmacokinetic parameters is 
not considered clinically 
significant.

Dose adjustments of diltiazem 
should be guided by clinical 
response (refer to the Summary of 
Product Characteristics for 
diltiazem). No dose adjustment is 
necessary for efavirenz.

Verapamil, Felodipine, Nifedipine 
and Nicardipine

Interaction not studied. When
efavirenz is co-administered with 
a calcium channel blocker that is 
a substrate of the 
CYP3A4 enzyme, there is a 
potential for reduction in the 
plasma concentrations of the 
calcium channel blocker.

Dose adjustments of calcium 
channel blockers should be guided 
by clinical response (refer to the 
Summary of Product 
Characteristics for the calcium 
channel blocker).

LIPID LOWERING MEDICINAL PRODUCTS

HMG Co-A Reductase Inhibitors
Atorvastatin/Efavirenz
(10 mg once daily/600 mg once daily)

Atorvastatin:
AUC: ↓ 43 % (↓ 34 to ↓ 50)
Cmax: ↓ 12 % (↓ 1 to ↓ 26)
2-hydroxy atorvastatin:
AUC: ↓ 35 % (↓ 13 to ↓ 40)
Cmax: ↓ 13 % (↓ 0 to ↓ 23)
4-hydroxy atorvastatin:
AUC: ↓ 4 % (↓ 0 to ↓ 31)
Cmax: ↓ 47 % (↓ 9 to ↓ 51)
Total active HMG Co-A 
reductase inhibitors: 
AUC: ↓ 34 % (↓ 21 to ↓ 41)
Cmax: ↓ 20 % (↓ 2 to ↓ 26)

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of atorvastatin may be 
required (refer to the Summary of 
Product Characteristics for the 
atorvastatin). No dose adjustment 
is necessary for efavirenz.

 



18

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Pravastatin/Efavirenz
(40 mg once daily/600 mg once daily)

Pravastatin:
AUC: ↓ 40 % (↓ 26 to ↓ 57)
Cmax: ↓ 18 % (↓ 59 to ↑ 12)

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of pravastatin may be 
required (refer to the Summary of 
Product Characteristics for 
pravastatin). No dose adjustment 
is necessary for efavirenz.

Simvastatin/Efavirenz
(40 mg once daily/600 mg once daily)

Simvastatin:
AUC: ↓ 69 % (↓ 62 to ↓ 73)
Cmax: ↓ 76 % (↓ 63 to ↓ 79)
Simvastatin acid:
AUC: ↓ 58 % (↓ 39 to ↓ 68)
Cmax: ↓ 51 % (↓ 32 to ↓ 58)
Total active HMG Co-A 
reductase inhibitors:
AUC: ↓ 60 % (↓ 52 to ↓ 68)
Cmax: ↓ 62 % (↓ 55 to ↓ 78)
(CYP3A4 induction)
Co-administration of efavirenz 
with atorvastatin, pravastatin, or 
simvastatin did not affect 
efavirenz AUC or Cmax values.

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of simvastatin may be 
required (refer to the Summary of 
Product Characteristics for 
simvastatin). No dose adjustment 
is necessary for efavirenz.

Rosuvastatin/Efavirenz Interaction not studied. 
Rosuvastatin is largely excreted 
unchanged via the faeces, 
therefore interaction with 
efavirenz is not expected.

No dose adjustment is necessary 
for either medicinal product.

HORMONAL CONTRACEPTIVES
Oral:
Ethinyloestradiol+Norgestimate/ 
Efavirenz
(0.035 mg+0.25 mg once 
daily/600 mg once daily)

Ethinyloestradiol:
AUC: ↔
Cmax: ↔
Cmin: ↓ 8 % (↑ 14 to ↓ 25)
Norelgestromin (active 
metabolite):
AUC: ↓ 64 % (↓ 62 to ↓ 67)
Cmax: ↓ 46 % (↓ 39 to ↓ 52)
Cmin: ↓ 82 % (↓ 79 to ↓ 85)
Levonorgestrel (active 
metabolite):
AUC: ↓ 83 % (↓ 79 to ↓ 87)
Cmax: ↓ 80 % (↓ 77 to ↓ 83)
Cmin: ↓ 86 % (↓ 80 to ↓ 90)
(induction of metabolism)
Efavirenz: no clinically 
significant interaction.
The clinical significance of these 
effects is not known.

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6).

 



19

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Injection: Depo-medroxyprogesterone 
acetate (DMPA)/Efavirenz
(150 mg IM single dose DMPA)

In a 3-month drug interaction 
study, no significant differences 
in MPA pharmacokinetic 
parameters were found between 
subjects receiving efavirenz-
containing antiretroviral therapy 
and subjects receiving no 
antiretroviral therapy. Similar 
results were found by other 
investigators, although the MPA 
plasma levels were more variable 
in the second study. In both 
studies, plasma progesterone 
levels for subjects receiving 
efavirenz and DMPA remained 
low consistent with suppression 
of ovulation.

Because of the limited information 
available, a reliable method of 
barrier contraception must be used 
in addition to hormonal 
contraceptives (see section 4.6).

Implant: Etonogestrel/Efavirenz Decreased exposure of 
etonogestrel may be expected 
(CYP3A4 induction). There have 
been occasional postmarketing 
reports of contraceptive failure 
with etonogestrel in efavirenz-
exposed patients.

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6).

IMMUNOSUPPRESSANTS
Immunosuppressants metabolized by 
CYP3A4 (e.g., cyclosporine, 
tacrolimus, sirolimus)/Efavirenz

Interaction not studied. Decreased 
exposure of the 
immunosuppressant may be 
expected (CYP3A4 induction). 
These immunosuppressants are 
not anticipated to affect exposure 
of efavirenz.

Dose adjustments of the 
immunosuppressant may be 
required. Close monitoring of 
immunosuppressant 
concentrations for at least 2 weeks 
(until stable concentrations are 
reached) is recommended when 
starting or stopping treatment with 
efavirenz.

OPIOIDS
Methadone/Efavirenz
(stable maintenance, 35-100 mg once 
daily/600 mg once daily)

Methadone:
AUC: ↓ 52 % (↓ 33 to ↓ 66)
Cmax: ↓ 45 % (↓ 25 to ↓ 59)
(CYP3A4 induction)
In a study of HIV infected 
intravenous drug users, 
co-administration of efavirenz 
with methadone resulted in 
decreased plasma levels of 
methadone and signs of opiate 
withdrawal. The methadone dose 
was increased by a mean of 22 % 
to alleviate withdrawal 
symptoms.

Concomitant administration with 
efavirenz should be avoided due to 
the risk for QTc prolongation (see 
section 4.3).

Buprenorphine/naloxone/Efavirenz Buprenorphine:
AUC: ↓ 50 %
Norbuprenorphine:
AUC: ↓ 71 %
Efavirenz:
No clinically significant 
pharmacokinetic interaction

Despite the decrease in 
buprenorphine exposure, no 
patients exhibited withdrawal 
symptoms. Dose adjustment of 
buprenorphine or efavirenz may 
not be necessary when 
co-administered.

a 90 % confidence intervals unless otherwise noted.

 



20

b 95 % confidence intervals.

Other interactions: efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid 
test results have been reported with some screening assays in uninfected and HIV-infected subjects 
receiving efavirenz. Confirmatory testing by a more specific method such as gas 
chromatography/mass spectrometry is recommended in such cases.

4.6 Fertility, pregnancy and lactation

Contraception in males and females

Barrier contraception should always be used in combination with other methods of contraception (for 
example, oral or other hormonal contraceptives, see section 4.5). Because of the long half-life of 
efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is 
recommended.

Pregnancy

Efavirenz should not be used during pregnancy, unless the patient’s clinical condition requires such 
treatment. Women of childbearing potential should undergo pregnancy testing before initiation of 
efavirenz (see section 5.3).

There have been seven retrospective reports of findings consistent with neural tube defects, including 
meningomyelocele, all in mothers exposed to efavirenz-containing regimens (excluding any 
efavirenz-containing fixed-dose combination tablets) in the first trimester. Two additional cases 
(1 prospective and 1 retrospective) including events consistent with neural tube defects have been 
reported with a fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir 
disoproxil. A causal relationship of these events to the use of efavirenz has not been established, and 
the denominator is unknown. As neural tube defects occur within the first 4 weeks of foetal 
development (at which time neural tubes are sealed), this potential risk would concern women exposed 
to efavirenz during the first trimester of pregnancy.

As of July 2013, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 
904 pregnancies with first trimester exposure to efavirenz-containing regimens, resulting in 766 live 
births. One child was reported to have a neural tube defect, and the frequency and pattern of other 
birth defects were similar to those seen in children exposed to non-efavirenz-containing regimens, as 
well as those in HIV negative controls. The incidence of neural tube defects in the general population 
ranges from 0.5-1 case per 1,000 live births.

Malformations have been observed in foetuses from efavirenz-treated monkeys (see section 5.3).

Breast-feeding

Efavirenz has been shown to be excreted in human milk. There is insufficient information on the 
effects of efavirenz in newborns/infants. Risk to the infant can not be excluded. Breast-feeding should 
be discontinued during treatment with efavirenz. It is recommended that HIV infected women do not 
breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Fertility

The effect of efavirenz on male and female fertility in rats has only been evaluated at doses that 
achieved systemic drug exposures equivalent to or below those achieved in humans given 
recommended doses of efavirenz. In these studies, efavirenz did not impair mating or fertility of male 
or female rats (doses up to 100 mg/kg/bid), and did not affect sperm or offspring of treated male rats 
(doses up to 200 mg/bid). The reproductive performance of offspring born to female rats given 
efavirenz was not affected.

 



21

4.7 Effects on ability to drive and use machines

Efavirenz may cause dizziness, impaired concentration, and/or somnolence. Patients should be 
instructed that if they experience these symptoms they should avoid potentially hazardous tasks such 
as driving or operating machinery.

4.8 Undesirable effects

Summary of the safety profile

Efavirenz has been studied in over 9,000 patients. In a subset of 1,008 adult patients who received 
600 mg efavirenz daily in combination with PIs and/or NRTIs in controlled clinical studies, the most 
frequently reported adverse reactions of at least moderate severity reported in at least 5 % of patients 
were rash (11.6 %), dizziness (8.5 %), nausea (8.0 %), headache (5.7 %) and fatigue (5.5 %). The most 
notable adverse reactions associated with efavirenz are rash and nervous system symptoms 
(see section 4.4). Nervous system symptoms usually begin soon after therapy onset and generally 
resolve after the first 2 - 4 weeks. Severe skin reactions such as Stevens-Johnson syndrome and 
erythema multiforme; psychiatric adverse reactions including severe depression, death by suicide, and 
psychosis like behaviour; and seizures have been reported in patients treated with efavirenz.

The long-term safety profile of efavirenz-containing regimens was evaluated in a controlled trial (006) 
in which patients received efavirenz + zidovudine + lamivudine (n = 412, median duration 
180 weeks), efavirenz + indinavir (n = 415, median duration 102 weeks), or indinavir + zidovudine + 
lamivudine (n = 401, median duration 76 weeks). Long-term use of efavirenz in this study was not 
associated with any new safety concerns.

Tabulated list of adverse reactions

Adverse reactions of moderate or greater severity with at least possible relationship to treatment 
regimen (based on investigator attribution) reported in clinical trials of efavirenz at the recommended 
dose in combination therapy (n = 1,008) are listed below. Also listed in italics are adverse reactions 
observed post-marketing in association with efavirenz-containing antiretroviral treatment regimens. 
Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100, 
< 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); or very rare (< 1/10,000).

 



22

Immune system disorders
uncommon hypersensitivity

Metabolism and nutrition disorders
common hypertriglyceridaemia*

uncommon hypercholesterolaemia*

Psychiatric disorders
common abnormal dreams, anxiety, depression, insomnia*

uncommon affect lability, aggression, confusional state, 
euphoric mood, hallucination, mania, paranoia, 
psychosis‡, suicide attempt, suicide ideation, 
catatonia*

rare delusion‡‡, neurosis‡‡, completed suicide‡‡*

Nervous system disorders
common cerebellar coordination and balance 

disturbances‡, disturbance in attention (3.6 %), 
dizziness (8.5 %), headache (5.7 %), somnolence 
(2.0 %)*

uncommon agitation, amnesia, ataxia, coordination abnormal, 
convulsions, thinking abnormal, tremor‡

Eye disorders
uncommon vision blurred

Ear and labyrinth disorders
uncommon tinnitus‡, vertigo

Vascular disorders
uncommon flushing‡

Gastrointestinal disorders
common abdominal pain, diarrhoea, nausea, vomiting

uncommon pancreatitis 

Hepatobiliary disorders
common aspartate aminotransferase (AST) increased*, 

alanine aminotransferase (ALT) increased*, 
gamma-glutamyltransferase (GGT) increased*

uncommon hepatitis acute

rare hepatic failure‡‡*

 



23

Skin and subcutaneous tissue disorders
very common rash (11.6 %)*

common pruritus

uncommon erythema multiforme, Stevens-Johnson 
syndrome*

rare photoallergic dermatitis‡

Reproductive system and breast disorders
uncommon gynaecomastia

General disorders and administration site conditions
common fatigue

*,‡ ,‡‡ See section Description of selected adverse reactions for more details.

Description of selected adverse reactions

Information regarding post-marketing surveillance
‡ These adverse reactions were identified through post-marketing surveillance; however, the 
frequencies were determined using data from 16 clinical trials (n=3,969). 

‡‡These adverse reactions were identified through post-marketing surveillance but not reported as 
drug-related events for efavirenz-treated patients in 16 clinical trials. The frequency category of "rare" 
was defined per A Guideline on Summary of Product Characteristics (SmPC) (rev. 2, Sept 2009) on 
the basis of an estimated upper bound of the 95% confidence interval for 0 events given the number of 
patients treated with efavirenz in these clinical trials (n=3,969).

Rash
In clinical studies, 26 % of patients treated with 600 mg of efavirenz experienced skin rash compared 
with 17 % of patients treated in control groups. Skin rash was considered treatment related in 18 % of 
patients treated with efavirenz. Severe rash occurred in less than 1 % of patients treated with efavirenz, 
and 1.7 % discontinued therapy because of rash. The incidence of erythema multiforme or 
Stevens-Johnson syndrome was approximately 0.1 %.

Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first two 
weeks of initiating therapy with efavirenz. In most patients rash resolves with continuing therapy with 
efavirenz within one month. Efavirenz can be reinitiated in patients interrupting therapy because of 
rash. Use of appropriate antihistamines and/or corticosteroids is recommended when efavirenz is 
restarted.

Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class 
is limited. Reported rates of recurrent rash following a switch from nevirapine to efavirenz therapy, 
primarily based on retrospective cohort data from published literature, range from 13 to 18 %, 
comparable to the rate observed in patients treated with efavirenz in clinical studies. (See section 4.4.)

 



24

Psychiatric symptoms
Serious psychiatric adverse reactions have been reported in patients treated with efavirenz. In 
controlled trials the frequency of specific serious psychiatric events were:

Efavirenz regimen
(n=1,008)

Control regimen
(n=635)

- severe depression 1.6 % 0.6 %
- suicidal ideation 0.6 % 0.3 %
- non-fatal suicide attempts 0.4 % 0 %
- aggressive behaviour 0.4 % 0.3 %
- paranoid reactions 0.4 % 0.3 %
- manic reactions 0.1 % 0 %

Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric 
adverse reactions with frequencies of each of the above events ranging from 0.3 % for manic reactions 
to 2.0 % for both severe depression and suicidal ideation. There have also been post-marketing reports 
of death by suicide, delusions, psychosis-like behaviour and catatonia.

Nervous system symptoms
In clinical controlled trials, frequently reported adverse reactions included, but were not limited to: 
dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. Nervous system 
symptoms of moderate-to-severe intensity were experienced by 19 % (severe 2.0 %) of patients 
compared to 9 % (severe 1 %) of patients receiving control regimens. In clinical studies 2 % of 
patients treated with efavirenz discontinued therapy due to such symptoms.

Nervous system symptoms usually begin during the first one or two days of therapy and generally 
resolve after the first 2 - 4 weeks. In a study of uninfected volunteers, a representative nervous system 
symptom had a median time to onset of 1 hour post-dose and a median duration of 3 hours. Nervous 
system symptoms may occur more frequently when efavirenz is taken concomitantly with meals 
possibly due to increased efavirenz plasma levels (see section 5.2). Dosing at bedtime seems to 
improve the tolerability of these symptoms and can be recommended during the first weeks of therapy 
and in patients who continue to experience these symptoms (see section 4.2). Dose reduction or 
splitting the daily dose has not been shown to provide benefit.

Analysis of long-term data showed that, beyond 24 weeks of therapy, the incidences of new-onset 
nervous system symptoms among efavirenz-treated patients were generally similar to those in the 
control arm.

Hepatic failure
A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing 
hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing 
in some cases to transplantation or death.

Immune Reactivation Syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have 
also been reported; however, the reported time to onset is more variable and these events can occur 
many months after initiation of treatment (see section 4.4).

Osteonecrosis
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk 
factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 
The frequency of this is unknown (see section 4.4).

 



25

Laboratory test abnormalities
Liver enzymes: elevations of AST and ALT to greater than five times the upper limit of the normal 
range (ULN) were seen in 3 % of 1,008 patients treated with 600 mg of efavirenz (5-8 % after long-
term treatment in study 006). Similar elevations were seen in patients treated with control regimens 
(5 % after long-term treatment). Elevations of GGT to greater than five times ULN were observed in 
4 % of all patients treated with 600 mg of efavirenz and 1.5 - 2 % of patients treated with control 
regimens (7 % of efavirenz-treated patients and 3 % of control-treated patients after long-term 
treatment). Isolated elevations of GGT in patients receiving efavirenz may reflect enzyme induction.
In the long-term study (006), 1 % of patients in each treatment arm discontinued because of liver or 
biliary system disorders.

Amylase: in the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels 
greater than 1.5 times the upper limit of normal were seen in 10 % of patients treated with efavirenz 
and 6 % of patients treated with control regimens. The clinical significance of asymptomatic increases 
in serum amylase is unknown.

Metabolic parameters
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4).

Paediatric population

Undesirable effects in children were generally similar to those of adult patients. Rash was reported 
more frequently in children (in a clinical study including 57 children who received efavirenz during a 
48-week period, rash was reported in 46 %) and was more often of higher grade than in adults (severe 
rash was reported in 5.3 % of children). Prophylaxis with appropriate antihistamines prior to initiating 
therapy with efavirenz in children may be considered. Although nervous system symptoms are 
difficult for young children to report, they appear to be less frequent in children and were generally 
mild. In the study of 57 children, 3.5 % of patients experienced nervous system symptoms of moderate 
intensity, predominantly dizziness. No child had severe symptoms or had to discontinue because of 
nervous system symptoms. Diarrhoea occurred in six of nineteen (32 %) children, aged 3 – 8 years, 
who took efavirenz oral solution in combination with nelfinavir (20 – 30 mg/kg given three times a 
day) and one or more NRTIs.

Other special populations

Liver enzymes in hepatitis B or C co-infected patients
In the long-term data set from study 006, 137 patients treated with efavirenz-containing regimens 
(median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 
56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/or C (hepatitis 
C antibody positive). Among co-infected patients in study 006, elevations in AST to greater than five 
times ULN developed in 13 % of efavirenz treated patients and in 7 % of controls, and elevations in 
ALT to greater than five times ULN developed in 20 % and 7 % respectively. Among co-infected 
patients, 3 % of those treated with efavirenz and 2 % in the control arm discontinued because of liver 
disorders (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Some patients accidentally taking 600 mg twice daily have reported increased nervous system 
symptoms. One patient experienced involuntary muscle contractions.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


26

Treatment of overdose with efavirenz should consist of general supportive measures, including 
monitoring of vital signs and observation of the patient’s clinical status. Administration of activated 
charcoal may be used to aid removal of unabsorbed efavirenz. There is no specific antidote for 
overdose with efavirenz. Since efavirenz is highly protein bound, dialysis is unlikely to remove 
significant quantities of it from blood.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antivirals for systemic use. Non-nucleoside reverse transcriptase 
inhibitors. ATC code: J05A G03

Mechanism of action

Efavirenz is a NNRTI of HIV-1. Efavirenz is a non-competitive inhibitor of HIV-1 reverse 
transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases (, , 
or ).

Cardiac Electrophysiology

The effect of efavirenz on the QTc interval was evaluated in an open-label, positive and placebo 
controlled, fixed single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects 
enriched for CYP2B6 polymorphisms. The mean Cmax of efavirenz in subjects with CYP2B6 *6/*6 
genotype following the administration of 600 mg daily dose for 14 days was 2.25-fold the mean Cmax
observed in subjects with CYP2B6 *1/*1 genotype. A positive relationship between efavirenz 
concentration and QTc prolongation was observed. Based on the concentration-QTc relationship, the 
mean QTc prolongation and its upper bound 90% confidence interval are 8.7 ms and 11.3 ms in 
subjects with CYP2B6*6/*6 genotype following the administration of 600 mg daily dose for 14 days 
(see section 4.5).

Antiviral activity

The free concentration of efavirenz required for 90 to 95 % inhibition of wild type or 
zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in 
lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/monocyte 
cultures.

Resistance

The potency of efavirenz in cell culture against viral variants with amino acid substitutions at positions 
48, 108, 179, 181 or 236 in RT or variants with amino acid substitutions in the protease was similar to 
that observed against wild type viral strains. The single substitutions which led to the highest 
resistance to efavirenz in cell culture correspond to a leucine-to-isoleucine change at position 100 
(L100I, 17 to 22-fold resistance) and a lysine-to-asparagine at position 103 (K103N, 18 to 33-fold 
resistance). Greater than 100-fold loss of susceptibility was observed against HIV variants expressing 
K103N in addition to other amino acid substitutions in RT.

K103N was the most frequently observed RT substitution in viral isolates from patients who 
experienced a significant rebound in viral load during clinical studies of efavirenz in combination with 
indinavir or zidovudine + lamivudine. This mutation was observed in 90 % of patients receiving 
efavirenz with virological failure. Substitutions at RT positions 98, 100, 101, 108, 138, 188, 190 or 
225 were also observed, but at lower frequencies, and often only in combination with K103N. The 
pattern of amino acid substitutions in RT associated with resistance to efavirenz was independent of 
the other antiviral medicinal products used in combination with efavirenz.

 



27

Cross-resistance

Cross resistance profiles for efavirenz, nevirapine and delavirdine in cell culture demonstrated that the 
K103N substitution confers loss of susceptibility to all three NNRTIs. Two of three 
delavirdine-resistant clinical isolates examined were cross-resistant to efavirenz and contained the 
K103N substitution. A third isolate which carried a substitution at position 236 of RT was not 
cross-resistant to efavirenz.

Viral isolates recovered from PBMCs of patients enrolled in efavirenz clinical studies who showed 
evidence of treatment failure (viral load rebound) were assessed for susceptibility to NNRTIs. Thirteen 
isolates previously characterised as efavirenz-resistant were also resistant to nevirapine and 
delavirdine. Five of these NNRTI-resistant isolates were found to have K103N or a 
valine-to-isoleucine substitution at position 108 (V108I) in RT. Three of the efavirenz treatment 
failure isolates tested remained sensitive to efavirenz in cell culture and were also sensitive to 
nevirapine and delavirdine.

The potential for cross resistance between efavirenz and PIs is low because of the different enzyme 
targets involved. The potential for cross-resistance between efavirenz and NRTIs is low because of the 
different binding sites on the target and mechanism of action.

Clinical efficacy

Efavirenz has not been studied in controlled studies in patients with advanced HIV disease, namely 
with CD4 counts < 50 cells/mm3, or in PI or NNRTI-experienced patients. Clinical experience in 
controlled studies with combinations including didanosine or zalcitabine is limited.

Two controlled studies (006 and ACTG 364) of approximately one year duration with efavirenz in 
combination with NRTIs and/or PIs, have demonstrated reduction of viral load below the limit of 
quantification of the assay and increased CD4 lymphocytes in antiretroviral therapy-naïve and 
NRTI-experienced HIV-infected patients. Study 020 showed similar activity in NRTI-experienced 
patients over 24 weeks. In these studies the dose of efavirenz was 600 mg once daily; the dose of 
indinavir was 1,000 mg every 8 hours when used with efavirenz and 800 mg every 8 hours when used 
without efavirenz. The dose of nelfinavir was 750 mg given three times a day. The standard doses of 
NRTIs given every 12 hours were used in each of these studies.

Study 006, a randomized, open-label trial, compared efavirenz + zidovudine + lamivudine or 
efavirenz + indinavir with indinavir + zidovudine + lamivudine in 1,266 patients who were required to 
be efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry. The mean baseline CD4 cell count 
was 341 cells/mm3 and the mean baseline HIV-RNA level was 60,250 copies/ml. Efficacy results for 
study 006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 3. 
In the analysis of responder rates (the non-completer equals failure analysis [NC = F]), patients who 
terminated the study early for any reason, or who had a missing HIV-RNA measurement that was 
either preceded or followed by a measurement above the limit of assay quantification were considered 
to have HIV-RNA above 50 or above 400 copies/ml at the missing time points.

 



28

Table 3: Efficacy results for study 006

Responder rates (NC = Fa)
Plasma HIV-RNA

Mean change 
from 

baseline-CD4 
cell count

< 400 copies/ml 
(95 % C.I.b)

< 50 copies/ml 
(95 % C.I.b)

cells/mm3 

(S.E.M.c)
Treatment 
Regimend

n 48 weeks 48 weeks 48 weeks

EFV + 
ZDV + 3TC

202 67 %
(60 %, 73 %)

62 %
(55 %, 69 %)

187
(11.8)

EFV + IDV 206 54 %
(47 %, 61 %)

48 %
(41 %, 55 %)

177
(11.3)

IDV + 
ZDV + 3TC

206 45 %
(38 %, 52 %)

40 %
(34 %, 47 %)

153
(12.3)

a NC = F, noncompleter = failure.
b C.I., confidence interval.
c S.E.M., standard error of the mean.
d EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir.

Long-term results at 168 weeks of study 006 (160 patients completed study on treatment with 
EFV +IDV, 196 patients with EFV + ZDV + 3TC and 127 patients with IDV + ZDV + 3TC, 
respectively), suggest durability of response in terms of proportions of patients with HIV RNA 
< 400 copies/ml, HIV RNA < 50 copies/ml and in terms of mean change from baseline CD4 cell 
count.

Efficacy results for studies ACTG 364 and 020 are found in Table 4. Study ACTG 364 enrolled 
196 patients who had been treated with NRTIs but not with PIs or NNRTIs. Study 020 enrolled 
327 patients who had been treated with NRTIs but not with PIs or NNRTIs. Physicians were allowed 
to change their patient’s NRTI regimen upon entry into the study. Responder rates were highest in 
patients who switched NRTIs.

Table 4: Efficacy results for studies ACTG 364 and 020

Responder rates (NC = Fa)
Plasma HIV-RNA

Mean change from 
baseline-CD4 cell count

Study Number/
Treatment Regimensb

n % (95 % C.I.c) % (95 % C.I.) cells/mm3 (S.E.M.d)

Study ACTG 364
48 weeks

< 500 copies/ml < 50 copies/ml

EFV + NFV + NRTIs 65 70 (59, 82) --- --- 107 (17.9)
EFV + NRTIs 65 58 (46, 70) --- --- 114 (21.0)
NFV + NRTIs 66 30 (19, 42) --- --- 94 (13.6)

Study 020
24 weeks

< 400 copies/ml < 50 copies/ml

EFV + IDV + NRTIs 157 60 (52, 68) 49 (41, 58) 104 (9.1)
IDV + NRTIs 170 51 (43, 59) 38 (30, 45) 77 (9.9)

a NC = F, noncompleter = failure.
b EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir; NRTI, nucleoside reverse transcriptase inhibitor; 
NFV, nelfinavir.
c C.I., confidence interval for proportion of patients in response.
d S.E.M., standard error of the mean.
---, not performed.

 



29

Paediatric population: ACTG 382 is an ongoing uncontrolled study of 57 NRTI-experienced 
paediatric patients (3 - 16 years) which characterises the pharmacokinetics, antiviral activity and safety 
of efavirenz in combination with nelfinavir (20 - 30 mg/kg given three times a day) and one or more 
NRTIs. The starting dose of efavirenz was the equivalent of a 600 mg dose (adjusted from calculated 
body size based on weight). The response rate, based on the NC = F analysis of the percentage of 
patients with plasma HIV-RNA < 400 copies/ml at 48 weeks was 60 % (95 %, C.I. 47, 72), and 53 % 
(C.I. 40, 66) based on percentage of patients with plasma HIV-RNA < 50 copies/ml. The mean CD4 
cell counts were increased by 63  34.5 cells/mm3 from baseline. The durability of the response was 
similar to that seen in adult patients.

5.2 Pharmacokinetic properties

Absorption

Peak efavirenz plasma concentrations of 1.6 - 9.1 M were attained by 5 hours following single oral 
doses of 100 mg to 1,600 mg administered to uninfected volunteers. Dose related increases in Cmax and 
AUC were seen for doses up to 1,600 mg; the increases were less than proportional suggesting 
diminished absorption at higher doses. Time to peak plasma concentrations (3 - 5 hours) did not 
change following multiple dosing and steady-state plasma concentrations were reached in 6 - 7 days.

In HIV infected patients at steady state, mean Cmax, mean Cmin, and mean AUC were linear with 
200 mg, 400 mg, and 600 mg daily doses. In 35 patients receiving efavirenz 600 mg once daily, steady 
state Cmax was 12.9 ± 3.7 M (29 %) [mean ± S.D. (% C.V.)], steady state Cmin was 5.6 ± 3.2 M 
(57 %), and AUC was 184 ± 73 M·h (40 %).

Effect of food

The AUC and Cmax of a single 240 mg dose of efavirenz oral solution in uninfected adult volunteers
was increased by 30 % and 43 % respectively, when given with a high-fat meal, relative to fasted 
conditions.

Distribution

Efavirenz is highly bound (approximately 99.5 - 99.75 %) to human plasma proteins, predominantly 
albumin. In HIV-1 infected patients (n = 9) who received efavirenz 200 to 600 mg once daily for at 
least one month, cerebrospinal fluid concentrations ranged from 0.26 to 1.19 % (mean 0.69 %) of the 
corresponding plasma concentration. This proportion is approximately 3-fold higher than the
non-protein-bound (free) fraction of efavirenz in plasma.

Biotransformation

Studies in humans and in vitro studies using human liver microsomes have demonstrated that 
efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with 
subsequent glucuronidation of these hydroxylated metabolites. These metabolites are essentially 
inactive against HIV-1. The in vitro studies suggest that CYP3A4 and CYP2B6 are the major 
isozymes responsible for efavirenz metabolism and that it inhibited P450 isozymes 2C9, 2C19, and 
3A4. In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at 
concentrations well above those achieved clinically.

Efavirenz plasma exposure may be increased in patients with the homozygous G516T genetic variant 
of the CYP2B6 isoenzyme. The clinical implications of such an association are unknown; however, 
the potential for an increased frequency and severity of efavirenz-associated adverse events cannot be 
excluded.

Efavirenz has been shown to induce CYP3A4 and CYP2B6, resulting in the induction of its own 
metabolism which may be clinically relevant in some patients. In uninfected volunteers, multiple 
doses of 200 - 400 mg per day for 10 days resulted in a lower than predicted extent of accumulation 

 



30

(22 - 42 % lower) and a shorter terminal half-life compared with single dose administration (see 
below). Efavirenz has also been shown to induce UGT1A1. Exposures of raltegravir (a UGT1A1 
substrate) are reduced in the presence of efavirenz (see section 4.5, table 2).
Although in vitro data suggest that efavirenz inhibits CYP2C9 and CYP2C19, there have been 
contradictory reports of both increased and decreased exposures to substrates of these enzymes when 
coadministered with efavirenz in vivo. The net effect of co-administration is not clear.

Elimination

Efavirenz has a relatively long terminal half-life of at least 52 hours after single doses and 
40 - 55 hours after multiple doses. Approximately 14 - 34 % of a radiolabelled dose of efavirenz was 
recovered in the urine and less than 1 % of the dose was excreted in urine as unchanged efavirenz.

Hepatic impairment

In a single-dose study, half life was doubled in the single patient with severe hepatic impairment 
(Child-Pugh Class C), indicating a potential for a much greater degree of accumulation. A multiple-
dose study showed no significant effect on efavirenz pharmacokinetics in patients with mild hepatic 
impairment (Child-Pugh Class A) compared with controls. There were insufficient data to determine 
whether moderate or severe hepatic impairment (Child-Pugh Class B or C) affects efavirenz 
pharmacokinetics.

Gender, race, elderly

Although limited data suggest that females as well as Asian and Pacific Island patients may have 
higher exposure to efavirenz, they do not appear to be less tolerant of efavirenz. Pharmacokinetic 
studies have not been performed in the elderly.

Paediatric population

In 17 paediatric patients receiving an investigational oral solution similar to the commercial 
formulation adjusted on the basis of body size to be equivalent to an adult 600 mg capsule dose, the 
steady-state Cmax was 11.8 M, steady state Cmin was 5.2 M, and AUC was 188 M·h. In the subset 
of 6 children aged 3 – 5 who were compliant with their drug regimen, the mean AUC was 147 M·h, 
which was 23 % lower than expected. Therefore, the dosage recommendation provided in Table 1 
incorporates a higher dose of efavirenz oral solution for these younger children.

5.3 Preclinical safety data

Efavirenz was not mutagenic or clastogenic in conventional genotoxicity assays.

Efavirenz induced foetal resorptions in rats. Malformations were observed in 3 of 
20 foetuses/newborns from efavirenz-treated cynomolgus monkeys given doses resulting in plasma 
efavirenz concentrations similar to those seen in humans. Anencephaly and unilateral anophthalmia 
with secondary enlargement of the tongue were observed in one foetus, microophthalmia was 
observed in another foetus, and cleft palate was observed in a third foetus. No malformations were 
observed in foetuses from efavirenz-treated rats and rabbits.

Biliary hyperplasia was observed in cynomolgus monkeys given efavirenz for ≥ 1 year at a dose 
resulting in mean AUC values approximately 2-fold greater than those in humans given the 
recommended dose. The biliary hyperplasia regressed upon cessation of dosing. Biliary fibrosis has 
been observed in rats. Non-sustained convulsions were observed in some monkeys receiving efavirenz 
for ≥ 1 year, at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the 
recommended dose (see sections 4.4 and 4.8).

 



31

Carcinogenicity studies showed an increased incidence of hepatic and pulmonary tumours in female 
mice, but not in male mice. The mechanism of tumour formation and the potential relevance for 
humans are not known.

Carcinogenicity studies in male mice, male and female rats were negative. While the carcinogenic 
potential in humans is unknown, these data suggest that the clinical benefit of efavirenz outweighs the 
potential carcinogenic risk to humans.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Medium chain triglycerides
Benzoic acid (E210)
Strawberry/mint flavour

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years.

After first opening: 1 month.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and content of container

HDPE bottles with a child-resistant polypropylene closure containing 180 ml of oral solution. An oral 
syringe with a push-in bottle-neck adapter is included in the carton.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/005 - bottle

 



32

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 28 May 1999.
Date of latest renewal: 23 April 2014.

10. DATE OF REVISION OF THE TEXT

Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu.

 



33

1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 600 mg film-coated tablets
STOCRIN 50 mg film-coated tablets
STOCRIN 200 mg film-coated tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

STOCRIN 600 mg film-coated tablets
Each film-coated tablet contains 600 mg of efavirenz.

Excipient with known effect
Each film-coated tablet contains 249.6 mg of lactose (as monohydrate).

STOCRIN 50 mg film-coated tablets
Each film-coated tablet contains 50 mg of efavirenz.

Excipient with known effect
Each film-coated tablet contains 20.8 mg of lactose (as monohydrate).

STOCRIN 200 mg film-coated tablets
Each film-coated tablet contains 200 mg of efavirenz.

Excipient with known effect
Each film-coated tablet contains 83.2 mg of lactose (as monohydrate).

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Film-coated tablet

STOCRIN 600 mg film-coated tablets
Dark yellow, capsule-shaped, debossed with “225” on one side.

STOCRIN 50 mg film-coated tablets
Yellow, round, debossed with “113” on one side.

STOCRIN 200 mg film-coated tablets
Yellow, round, debossed with “223” on one side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

STOCRIN is indicated in antiviral combination treatment of human immunodeficiency virus-1 
(HIV-1) infected adults, adolescents and children 3 years of age and older.

STOCRIN has not been adequately studied in patients with advanced HIV disease, namely in patients 
with CD4 counts < 50 cells/mm3, or after failure of protease inhibitor (PI) containing regimens. 
Although cross-resistance of efavirenz with PIs has not been documented, there are at present 
insufficient data on the efficacy of subsequent use of PI based combination therapy after failure of 
regimens containing STOCRIN.

 



34

For a summary of clinical and pharmacodynamic information, see section 5.1.

4.2 Posology and method of administration

Therapy should be initiated by a physician experienced in the management of HIV infection.

Posology

Efavirenz must be given in combination with other antiretroviral medicines (see section 4.5).

In order to improve the tolerability of nervous system adverse reactions, bedtime dosing is 
recommended (see section 4.8).

Adults
The recommended dose of efavirenz in combination with nucleoside analogue reverse transcriptase 
inhibitors (NRTIs) with or without a PI (see section 4.5) is 600 mg orally, once daily.

Dose adjustment
If efavirenz is coadministered with voriconazole, the voriconazole maintenance dose must be 
increased to 400 mg every 12 hours and the efavirenz dose must be reduced by 50 %, i.e., to 300 mg 
once daily. When treatment with voriconazole is stopped, the initial dose of efavirenz should be 
restored (see section 4.5).

If efavirenz is coadministered with rifampicin to patients weighing 50 kg or more, an increase in the 
dose of efavirenz to 800 mg/day may be considered (see section 4.5).

Children and adolescents (3 to 17 years)
The recommended dose of efavirenz in combination with a PI and/or NRTIs for patients between 3 
and 17 years of age is described in Table 1. Efavirenz tablets must only be administered to children 
who are able to reliably swallow tablets.

Table 1
Paediatric dose to be administered once daily*

Body Weight Efavirenz
kg Dose (mg)

13 to < 15 200
15 to < 20 250
20 to < 25 300

25 to < 32.5 350
32.5 to < 40 400

≥ 40 600

 Efavirenz 50 mg, 200 mg and 600 mg film-coated tablets are available.

Special populations

Renal impairment
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1 % of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.4).

Hepatic impairment
Patients with mild liver disease may be treated with their normally recommended dose of efavirenz. 
Patients should be monitored carefully for dose-related adverse reactions, especially nervous system 
symptoms (see sections 4.3 and 4.4).

 



35

Paediatric population
The safety and efficacy of efavirenz in children below the age of 3 years or weighing less than 13 kg 
have not yet been established. Currently available data are described in sections 4.8, 5.1 and 5.2, but 
no recommendation on a posology can be made.

Method of administration

It is recommended that STOCRIN be taken on an empty stomach. The increased efavirenz 
concentrations observed following administration of STOCRIN with food may lead to an increase in 
frequency of adverse reactions (see sections 4.4 and 5.2).

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Patients with severe hepatic impairment (Child Pugh Class C) (see section 5.2).

Co-administration with terfenadine, astemizole, cisapride, midazolam, triazolam, pimozide, bepridil, 
or ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) 
because competition for CYP3A4 by efavirenz could result in inhibition of metabolism and create the 
potential for serious and/or life-threatening adverse reactions [for example, cardiac arrhythmias, 
prolonged sedation or respiratory depression] (see section 4.5).

Herbal preparations containing St. John’s wort (Hypericum perforatum) due to the risk of decreased 
plasma concentrations and reduced clinical effects of efavirenz (see section 4.5).

Patients with:
-         a family history of sudden death or of congenital prolongation of the QTc interval on 

electrocardiograms, or with any other clinical condition known to prolong the QTc interval.
-         a history of symptomatic cardiac arrythmias or with clinically relevant bradycardia or with 

congestive cardiac failure accompanied by reduced left ventricle ejection fraction.
-         severe disturbances of electrolyte balance e.g. hypokalaemia or hypomagnesaemia.

Patients taking drugs that are known to prolong the QTc interval (proarrhythmic). 
These drugs include:
- antiarrhythmics of classes IA and III,
- neuroleptics, antidepressive agents,
- certain antibiotics including some agents of the following classes: macrolides, fluoroquinolones, 

imidazole and triazole antifungal agents,
- certain non-sedating antihistamines (terfenadine, astemizole),
- cisapride,
- flecainide,
- certain antimalarials,
- methadone.

Co-administration with elbasvir/grazoprevir due to the expected significant decreases in elbasvir and 
grazoprevir plasma concentrations (see section 4.5). This effect is due to an induction of CYP3A4 or 
P-gp by efavirenz and is expected to result in the loss of virologic response of elbasvir/grazoprevir.

4.4 Special warnings and precautions for use

Efavirenz must not be used as a single agent to treat HIV or added on as a sole agent to a failing 
regimen. Resistant virus emerges rapidly when efavirenz is administered as monotherapy. The choice 
of new antiretroviral agent(s) to be used in combination with efavirenz should take into consideration 
the potential for viral cross-resistance (see section 5.1).

 



36

Co-administration of efavirenz with a fixed combination tablet containing efavirenz, emtricitabine, 
and tenofovir disoproxil, is not recommended unless needed for dose adjustment (for example, with 
rifampicin).

Co-administration of glecaprevir/pibrentasvir with efavirenz may significantly decrease plasma
concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect. 
Co-administration of glecaprevir/pibrentasvir with efavirenz is not recommended (see section 4.5).

Concomitant use of Ginkgo biloba extracts is not recommended (see section 4.5).

When prescribing medicinal products concomitantly with efavirenz, physicians should refer to the 
corresponding Summary of Product Characteristics.

While effective viral suppression with antiretroviral therapy has been proven to substantially reduce 
the risk of sexual transmission, a residual risk cannot be excluded. Precautions to prevent transmission 
should be taken in accordance with national guidelines.

If any antiretroviral medicinal product in a combination regimen is interrupted because of suspected 
intolerance, serious consideration should be given to simultaneous discontinuation of all antiretroviral
medicinal products. The antiretroviral medicinal products should be restarted at the same time upon 
resolution of the intolerance symptoms. Intermittent monotherapy and sequential reintroduction of 
antiretroviral agents is not advisable because of the increased potential for selection of resistant virus.

Rash

Mild-to-moderate rash has been reported in clinical studies with efavirenz and usually resolves with 
continued therapy. Appropriate antihistamines and/or corticosteroids may improve the tolerability and 
hasten the resolution of rash. Severe rash associated with blistering, moist desquamation or ulceration 
has been reported in less than 1 % of patients treated with efavirenz. The incidence of erythema 
multiforme or Stevens-Johnson syndrome was approximately 0.1 %. Efavirenz must be discontinued 
in patients developing severe rash associated with blistering, desquamation, mucosal involvement or 
fever. If therapy with efavirenz is discontinued, consideration should also be given to interrupting 
therapy with other antiretroviral agents to avoid development of resistant virus (see section 4.8).

Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class 
is limited (see section 4.8). Efavirenz is not recommended for patients who have had a life-threatening 
cutaneous reaction (e.g., Stevens-Johnson syndrome) while taking another NNRTI.

Psychiatric symptoms

Psychiatric adverse reactions have been reported in patients treated with efavirenz. Patients with a 
prior history of psychiatric disorders appear to be at greater risk of these serious psychiatric adverse 
reactions. In particular, severe depression was more common in those with a history of depression. 
There have also been post-marketing reports of severe depression, death by suicide, delusions,
psychosis-like behaviour and catatonia. Patients should be advised that if they experience symptoms 
such as severe depression, psychosis or suicidal ideation, they should contact their doctor immediately 
to assess the possibility that the symptoms may be related to the use of efavirenz, and if so, to 
determine whether the risks of continued therapy outweigh the benefits (see section 4.8).

Nervous system symptoms

Symptoms including, but not limited to, dizziness, insomnia, somnolence, impaired concentration and 
abnormal dreaming are frequently reported adverse reactions in patients receiving efavirenz 600 mg 
daily in clinical studies (see section 4.8). Nervous system symptoms usually begin during the first one 
or two days of therapy and generally resolve after the first 2 - 4 weeks. Patients should be informed 
that if they do occur, these common symptoms are likely to improve with continued therapy and are 
not predictive of subsequent onset of any of the less frequent psychiatric symptoms.

 



37

Seizures

Convulsions have been observed in patients receiving efavirenz, generally in the presence of known 
medical history of seizures. Patients who are receiving concomitant anticonvulsant medicinal products 
primarily metabolised by the liver, such as phenytoin, carbamazepine and phenobarbital, may require 
periodic monitoring of plasma levels. In a drug interaction study, carbamazepine plasma 
concentrations were decreased when carbamazepine was co-administered with efavirenz (see 
section 4.5). Caution must be taken in any patient with a history of seizures.

Hepatic events

A few of the postmarketing reports of hepatic failure occurred in patients with no pre-existing hepatic 
disease or other identifiable risk factors (see section 4.8). Liver enzyme monitoring should be 
considered for patients without pre-existing hepatic dysfunction or other risk factors.

QTc Prolongation

QTc prolongation has been observed with the use of efavirenz (see sections 4.5 and 5.1). 

Consider alternatives to efavirenz for co-administration with a drug with a known risk of Torsade de 
Pointes or when to be administered to patients at higher risk of Torsade de Pointes.

Effect of food

The administration of efavirenz with food may increase efavirenz exposure (see section 5.2) and may 
lead to an increase in the frequency of adverse reactions (see section 4.8). It is recommended that 
efavirenz be taken on an empty stomach, preferably at bedtime.

Immune Reactivation Syndrome

In HIV infected patients with severe immune deficiency at the time of institution of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
pathogens may arise and cause serious clinical conditions, or aggravation of symptoms. Typically, 
such reactions have been observed within the first few weeks or months of initiation of CART. 
Relevant examples are cytomegalovirus retinitis, generalised and/or focal mycobacterial infections, 
and pneumonia caused by Pneumocystis jiroveci (formerly known as Pneumocystis carinii). Any 
inflammatory symptoms should be evaluated and treatment instituted when necessary. Autoimmune 
disorders (such as Graves’ disease and autoimmune hepatitis) have also been reported to occur in the 
setting of immune reactivation; however, the reported time to onset is more variable and these events 
can occur many months after initiation of treatment.

Weight and metabolic parameters

An increase in weight and in levels of blood lipids and glucose may occur during antiretroviral 
therapy. Such changes may in part be linked to disease control and life style. For lipids, there is in 
some cases evidence for a treatment effect, while for weight gain there is no strong evidence relating 
this to any particular treatment. For monitoring of blood lipids and glucose reference is made to 
established HIV treatment guidelines. Lipid disorders should be managed as clinically appropriate.

Osteonecrosis

Although the aetiology is considered to be multifactorial (including corticosteroid use, alcohol 
consumption, severe immunosuppression, higher body mass index), cases of osteonecrosis have been 
reported particularly in patients with advanced HIV-disease and/or long-term exposure to combination 
antiretroviral therapy (CART). Patients should be advised to seek medical advice if they experience 
joint aches and pain, joint stiffness or difficulty in movement.

 



38

Special populations

Liver disease
Efavirenz is contraindicated in patients with severe hepatic impairment (see sections 4.3 and 5.2) and 
not recommended in patients with moderate hepatic impairment because of insufficient data to 
determine whether dose adjustment is necessary. Because of the extensive cytochrome P450-mediated 
metabolism of efavirenz and limited clinical experience in patients with chronic liver disease, caution 
must be exercised in administering efavirenz to patients with mild hepatic impairment. Patients should 
be monitored carefully for dose-related adverse reactions, especially nervous system symptoms. 
Laboratory tests should be performed to evaluate their liver disease at periodic intervals 
(see section 4.2).

The safety and efficacy of efavirenz has not been established in patients with significant underlying 
liver disorders. Patients with chronic hepatitis B or C and treated with combination antiretroviral 
therapy are at increased risk for severe and potentially fatal hepatic adverse reactions. Patients with 
pre-existing liver dysfunction including chronic active hepatitis have an increased frequency of liver 
function abnormalities during combination antiretroviral therapy and should be monitored according 
to standard practice. If there is evidence of worsening liver disease or persistent elevations of serum 
transaminases to greater than 5 times the upper limit of the normal range, the benefit of continued 
therapy with efavirenz needs to be weighed against the potential risks of significant liver toxicity. In 
such patients, interruption or discontinuation of treatment must be considered (see section 4.8).

In patients treated with other medicinal products associated with liver toxicity, monitoring of liver 
enzymes is also recommended. In case of concomitant antiviral therapy for hepatitis B or C, please 
refer also to the relevant product information for these medicinal products.

Renal insufficiency
The pharmacokinetics of efavirenz have not been studied in patients with renal insufficiency; however, 
less than 1 % of an efavirenz dose is excreted unchanged in the urine, so the impact of renal 
impairment on efavirenz elimination should be minimal (see section 4.2). There is no experience in 
patients with severe renal failure and close safety monitoring is recommended in this population.

Elderly patients
Insufficient numbers of older patients have been evaluated in clinical studies to determine whether 
they respond differently than younger patients.

Paediatric population
Efavirenz has not been evaluated in children below 3 years of age or who weigh less than 13 kg. 
Therefore, efavirenz should not be given to children less than 3 years of age.

Rash was reported in 26 of 57 children (46 %) treated with efavirenz during a 48-week period and was 
severe in three patients. Prophylaxis with appropriate antihistamines prior to initiating therapy with 
efavirenz in children may be considered.

Lactose

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or 
glucose-galactose malabsorption should not take this medicinal product. Individuals with these 
conditions may take efavirenz oral solution, which is free from lactose. 

4.5 Interaction with other medicinal products and other forms of interaction

Efavirenz is an in vivo inducer of CYP3A4, CYP2B6 and UGT1A1. Compounds that are substrates of 
these enzymes may have decreased plasma concentrations when co-administered with efavirenz. In 
vitro efavirenz is also an inhibitor of CYP3A4. Theoretically, efavirenz may therefore initially 
increase the exposure to CYP3A4 substrates and caution is warranted for CYP3A4 substrates with 

 



39

narrow therapeutic index (see section 4.3). Efavirenz may be an inducer of CYP2C19 and CYP2C9; 
however inhibition has also been observed in vitro and the net effect of co-administration with 
substrates of these enzymes is not clear (see section 5.2).

Efavirenz exposure may be increased when given with medicinal products (for example, ritonavir) or 
food (for example, grapefruit juice), which inhibit CYP3A4 or CYP2B6 activity. Compounds or 
herbal preparations (for example Ginkgo biloba extracts and St. John’s wort) which induce these 
enzymes may give rise to decreased plasma concentrations of efavirenz. Concomitant use of St. John’s 
wort is contraindicated (see section 4.3). Concomitant use of Ginkgo biloba extracts is not 
recommended (see section 4.4).

QT Prolonging Drugs

Efavirenz is contraindicated with concomitant use of drugs (they may cause prolonged QTc interval 
and Torsade de Pointes) such as: antiarrhythmics of classes IA and III, neuroleptics and antidepressant 
agents, certain antibiotics including some agents of the following classes: macrolides, 
fluoroquinolones, imidazole, and triazole antifungal agents, certain non-sedating antihistaminics 
(terfenadine, astemizole), cisapride, flecainide, certain antimalarials and methadone (see section 4.3).

Paediatric population

Interaction studies have only been performed in adults.

Contraindications of concomitant use

Efavirenz must not be administered concurrently with terfenadine, astemizole, cisapride, midazolam, 
triazolam, pimozide, bepridil, or ergot alkaloids (for example, ergotamine, dihydroergotamine, 
ergonovine, and methylergonovine) since inhibition of their metabolism may lead to serious, 
life-threatening events (see section 4.3).

Efavirenz must not be administered with elbasvir/grazoprevir due to the expected significant decreases
in elbasvir and grazoprevir plasma concentrations caused by induction of drug metabolising enzymes 
and/or transport proteins and which are expected to result in the loss of virologic response of 
elbasvir/grazoprevir (see section 4.5).

St. John’s wort (Hypericum perforatum)

Co-administration of efavirenz and St. John’s wort or herbal preparations containing St. John’s wort is 
contraindicated. Plasma levels of efavirenz can be reduced by concomitant use of St. John's wort due 
to induction of drug metabolising enzymes and/or transport proteins by St. John's wort. If a patient is 
already taking St. John’s wort, stop St. John’s wort, check viral levels and if possible efavirenz levels. 
Efavirenz levels may increase on stopping St. John’s wort and the dose of efavirenz may need 
adjusting. The inducing effect of St. John’s wort may persist for at least 2 weeks after cessation of 
treatment (see section 4.3).

Other interactions

Interactions between efavirenz and protease inhibitors, antiretroviral agents other than protease 
inhibitors and other non-antiretroviral medicinal products are listed in Table 2 below (increase is 
indicated as “↑”, decrease as “↓”, no change as “↔”, and once every 8 or 12 hours as “q8h” or 
“q12h”). If available, 90 % or 95 % confidence intervals are shown in parentheses. Studies were 
conducted in healthy subjects unless otherwise noted.

 



40

Table 2: Interactions between efavirenz and other medicinal products in adults

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

ANTI-INFECTIVES
HIV antivirals
Protease inhibitors (PI)
Atazanavir/ ritonavir/Efavirenz
(400 mg once daily/100 mg once 
daily/600 mg once daily, all 
administered with food)

Atazanavir (pm):
AUC: ↔* (↓ 9 to ↑ 10)
Cmax: ↑ 17 %* (↑ 8 to ↑ 27)
Cmin: ↓ 42 %* (↓ 31 to ↓ 51)

Co-administration of efavirenz 
with atazanavir/ritonavir is not 
recommended. If the 
co-administration of atazanavir 
with an NNRTI is required, an 
increase in the dose of both 
atazanavir and ritonavir to 400 mg 
and 200 mg, respectively, in 
combination with efavirenz could 
be considered with close clinical 
monitoring.

Atazanavir/ritonavir/Efavirenz
(400 mg once daily/200 mg once 
daily/600 mg once daily, all 
administered with food)

Atazanavir (pm):
AUC: ↔*/** (↓ 10 to ↑ 26)
Cmax: ↔*/** (↓ 5 to ↑ 26)
Cmin: ↑ 12 %*/** (↓ 16 to ↑ 49)
(CYP3A4 induction).
* When compared to atazanavir 
300 mg/ritonavir 100 mg once 
daily in the evening without 
efavirenz. This decrease in 
atazanavir Cmin might negatively 
impact the efficacy of atazanavir.
** based on historical comparison

Darunavir/ritonavir/Efavirenz
(300 mg twice daily*/100 mg twice 
daily/600 mg once daily)

*lower than recommended doses, 
similar findings are expected with 
recommended doses.

Darunavir:
AUC : ↓ 13 %
Cmin : ↓ 31 %
Cmax: ↓ 15%
(CYP3A4 induction)
Efavirenz:
AUC : ↑ 21 %
Cmin: ↑ 17 %
Cmax: ↑ 15%
(CYP3A4 inhibition)

Efavirenz in combination with 
darunavir/ritonavir 800/100 mg 
once daily may result in 
suboptimal darunavir Cmin. If 
efavirenz is to be used in 
combination with 
darunavir/ritonavir, the 
darunavir/ritonavir 600/100 mg 
twice daily regimen should be 
used. This combination should be 
used with caution.
See also ritonavir row below.

Fosamprenavir/ritonavir/Efavirenz
(700 mg twice daily/100 mg twice 
daily/600 mg once daily)

No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for any of these medicinal 
products. 
See also ritonavir row below.

Fosamprenavir/Nelfinavir/Efavirenz Interaction not studied No dose adjustment is necessary 
for any of these medicinal 
products.

Fosamprenavir/Saquinavir/Efavirenz Interaction not studied Not recommended, as the 
exposure to both PIs is expected to 
be significantly decreased.

Indinavir/Efavirenz
(800 mg q8h/200 mg once daily)

Indinavir:
AUC: ↓ 31 % (↓ 8 to ↓ 47)
Cmin: ↓ 40 %
A similar reduction in indinavir 
exposures was observed when 
indinavir 1,000 mg q8h was given 
with efavirenz 600 mg daily.
(CYP3A4 induction)
Efavirenz:
No clinically significant 
pharmacokinetic interaction

While the clinical significance of 
decreased indinavir concentrations 
has not been established, the 
magnitude of the observed 
pharmacokinetic interaction 
should be taken into consideration 
when choosing a regimen 
containing both efavirenz and 
indinavir.

No dose adjustment is necessary 
for efavirenz when given with 

 



41

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Indinavir/ritonavir/Efavirenz
(800 mg twice daily/100 mg twice 
daily/600 mg once daily)

Indinavir:
AUC: ↓ 25 % (↓ 16 to ↓ 32) b

Cmax: ↓ 17 % (↓ 6 to ↓ 26)
b

Cmin: ↓ 50 % (↓ 40 to ↓ 59)
b

Efavirenz:
No clinically significant 
pharmacokinetic interaction
The geometric mean Cmin for 
indinavir (0.33 mg/l) when given 
with ritonavir and efavirenz was 
higher than the mean historical 
Cmin (0.15 mg/l) when indinavir 
was given alone at 800 mg q8h. In 
HIV-1 infected patients (n = 6), 
the pharmacokinetics of indinavir 
and efavirenz were generally 
comparable to these uninfected 
volunteer data.

indinavir or indinavir/ritonavir.

See also ritonavir row below.

Lopinavir/ritonavir soft capsules or 
oral solution/Efavirenz

Lopinavir/ritonavir tablets/ Efavirenz

Substantial decrease in lopinavir 
exposure.

With efavirenz, an increase of the 
lopinavir/ritonavir soft capsule or 
oral solution doses by 33 % should 
be considered (4 capsules/~6.5 ml 
twice daily instead of 
3 capsules/5 ml twice daily). 
Caution is warranted since this 
dose adjustment might be 
insufficient in some patients. The 
dose of lopinavir/ritonavir tablets 
should be increased to 500/125 mg 
twice daily when co-administered
with efavirenz 600 mg once daily.
See also ritonavir row below.

(400/100 mg twice daily/600 mg once 
daily)

Lopinavir concentrations: 
↓ 30-40 %

(500/125 mg twice daily/600 mg once 
daily)

Lopinavir concentrations: similar 
to lopinavir/ritonavir 400/100 mg 
twice daily without efavirenz

Nelfinavir/Efavirenz
(750 mg q8h/600 mg once daily)

Nelfinavir:
AUC: ↑ 20 % (↑ 8 to ↑ 34)
Cmax: ↑ 21 % (↑ 10 to ↑ 33)
The combination was generally 
well tolerated.

No dose adjustment is necessary 
for either medicinal product.

 



42

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Ritonavir/Efavirenz
(500 mg twice daily/600 mg once 
daily)

Ritonavir:
Morning AUC: ↑ 18 % (↑ 6 to 
↑ 33)
Evening AUC: ↔
Morning Cmax: ↑ 24 % (↑ 12 to 
↑ 38)
Evening Cmax: ↔
Morning Cmin: ↑ 42 % (↑ 9 to 
↑ 86)b 

Evening Cmin: ↑ 24 % (↑ 3 to 
↑ 50)b

Efavirenz:
AUC: ↑ 21 % (↑ 10 to ↑ 34)
Cmax: ↑ 14 % (↑ 4 to ↑ 26)
Cmin: ↑ 25 % (↑ 7 to ↑ 46)

b

(inhibition of CYP-mediated 
oxidative metabolism)
When efavirenz was given with 
ritonavir 500 mg or 600 mg twice 
daily, the combination was not 
well tolerated (for example, 
dizziness, nausea, paraesthesia 
and elevated liver enzymes 
occurred). Sufficient data on the 
tolerability of efavirenz with 
low-dose ritonavir (100 mg, once 
or twice daily) are not available.  

When using efavirenz with 
low-dose ritonavir, the possibility 
of an increase in the incidence of 
efavirenz-associated adverse 
events should be considered, due 
to possible pharmacodynamic 
interaction.

Saquinavir/ritonavir/Efavirenz Interaction not studied. No data are available to make a 
dose recommendation. See also 
ritonavir row above. Use of 
efavirenz in combination with 
saquinavir as the sole protease 
inhibitor is not recommended.

CCR5 antagonist
Maraviroc/Efavirenz
(100 mg twice daily/600 mg once 
daily)

Maraviroc:
AUC12: ↓ 45 % (↓ 38 to ↓ 51)
Cmax: ↓ 51 % (↓ 37 to ↓ 62)
Efavirenz concentrations not 
measured, no effect is expected.

Refer to the Summary of Product 
Characteristics for the medicinal 
product containing maraviroc.

Integrase strand transfer inhibitor
Raltegravir/Efavirenz
(400 mg single dose/ - )

Raltegravir:
AUC: ↓ 36 %
C12: ↓ 21 %
Cmax: ↓ 36 %
(UGT1A1 induction)

No dose adjustment is necessary 
for raltegravir.

NRTIs and NNRTIs
NRTIs/Efavirenz Specific interaction studies have 

not been performed with efavirenz 
and NRTIs other than lamivudine, 
zidovudine, and tenofovir 
disoproxil. Clinically significant 
interactions are not expected since 
the NRTIs are metabolised via a 
different route than efavirenz and 
would be unlikely to compete for 
the same metabolic enzymes and 
elimination pathways.

No dose adjustment is necessary 
for either medicinal product.

 



43

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

NNRTIs/Efavirenz Interaction not studied. Since use of two NNRTIs proved 
not beneficial in terms of efficacy 
and safety, co-administration of 
efavirenz and another NNRTI is 
not recommended.

Hepatitis C antivirals
Boceprevir/Efavirenz
(800 mg 3 times daily/600 mg once 
daily)

Boceprevir:
AUC: ↔ 19%*
Cmax: ↔ 8%

Cmin: ↓ 44%
Efavirenz:
AUC: ↔ 20%
Cmax: ↔ 11%
(CYP3A induction - effect on 
boceprevir)
*0-8 hours
No effect (↔) equals a decrease 
in mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25%

Plasma trough concentrations of 
boceprevir were decreased when 
administered with efavirenz. The 
clinical outcome of this observed 
reduction of boceprevir trough 
concentrations has not been 
directly assessed.

Telaprevir/Efavirenz
(1,125 mg q8h/600 mg once daily)

Telaprevir (relative to 750 mg 
q8h):
AUC: ↓ 18% (↓ 8 to ↓ 27)
Cmax: ↓ 14% (↓ 3 to ↓ 24)

Cmin: ↓ 25% (↓ 14 to ↓ 34)%
Efavirenz:
AUC: ↓ 18% (↓ 10 to ↓ 26)
Cmax: ↓ 24% (↓ 15 to ↓ 32)

Cmin: ↓ 10% (↑ 1 to ↓ 19)%
(CYP3A induction by efavirenz)

If efavirenz and telaprevir are co-
administered, telaprevir 1,125 mg 
every 8 hours should be used.

Simeprevir/Efavirenz
(150 mg once daily /600 mg once 
daily)

Simeprevir: 
AUC: ↓ 71% (↓ 67 to ↓ 74)
Cmax: ↓ 51% (↓ 46 to ↓ 56)
Cmin: ↓ 91% (↓ 88 to ↓ 92)
Efavirenz:
AUC: ↔ 
Cmax: ↔
Cmin: ↔
No effect (↔) equals a decrease 
in mean ratio estimate of ≤20% or 
increase in mean ratio estimate of 
≤25%
(CYP3A4 enzyme induction)

Concomitant administration of 
simeprevir with efavirenz resulted 
in significantly decreased plasma 
concentrations of simeprevir due 
to CYP3A induction by efavirenz, 
which may result in loss of 
therapeutic effect of simeprevir. 
Co-administration of simeprevir
with efavirenz is not 
recommended.)

 



44

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Elbasvir/grazoprevir Elbasvir:
AUC: ↓54%
Cmax: ↓45%

Grazoprevir:
AUC: ↓83%
Cmax: ↓87%

Concomitant administration of 
STOCRIN with 
elbasvir/grazoprevir is 
contraindicated (see section 4.3) 
because it may lead to loss of 
virologic response to 
elbasvir/grazoprevir. This loss is 
due to significant decreases in 
elbasvir and grazoprevir plasma 
concentrations caused by CYP3A4
or P-gp induction (refer to the 
Summary of Product 
Characteristics for 
elbasvir/grazoprevir for additional
information).

Sofosbuvir/velpatasvir 
sofosbuvir/velpatasvir/voxilaprevir

Sofosbuvir:
Cmax ↑38%

Velpatasvir
AUC ↓53%
Cmax ↓47%
Cmin ↓57%

Expected:
↓ Voxilaprevir

Co-administration of 
efavirenz/emtricitabine/tenofovir 
disoproxil with 
sofosbuvir/velpatasvir has been 
shown to significantly decrease 
plasma concentrations of 
velpatasvir due to CYP3A 
induction by efavirenz, which may 
result in loss of therapeutic effect 
of velpatasvir. Although not 
studied, a similar decrease in 
voxilaprevir exposure is 
anticipated. Co-administration of 
STOCRIN with 
sofosbuvir/velpatasvir or 
sofosbuvir/velpatasvir/voxilaprevir 
is not recommended (refer to the 
Summary of Product 
Characteristics for 
sofosbuvir/velpatasvir and 
sofosbuvir/velpatasvir/voxilaprevir 
for additional information).

Glecaprevir/pibrentasvir ↓glecaprevir
↓pibrentasvir

Concomitant administration of 
glecaprevir/pibrentasvir with 
efavirenz may significantly 
decrease plasma concentrations 
of glecaprevir and pibrentasvir, 
leading to reduced therapeutic 
effect.
Co-administration of
glecaprevir/pibrentasvir with
efavirenz is not recommended. 
Refer to the prescribing 
information for
glecaprevir/pibrentasvir for
more information.

 



45

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Antibiotics
Azithromycin/Efavirenz
(600 mg single dose/400 mg once 
daily)

No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for either medicinal product.

Clarithromycin/Efavirenz
(500 mg q12h/400 mg once daily)

Clarithromycin:
AUC: ↓ 39 % (↓ 30 to ↓ 46)
Cmax: ↓ 26 % (↓ 15 to ↓ 35)
Clarithromycin 
14-hydroxymetabolite:
AUC: ↑ 34 % (↑ 18 to ↑ 53)
Cmax: ↑ 49 % (↑ 32 to ↑ 69)
Efavirenz:
AUC: ↔
Cmax: ↑ 11 % (↑ 3 to ↑ 19)
(CYP3A4 induction)
Rash developed in 46 % of 
uninfected volunteers receiving 
efavirenz and clarithromycin.

The clinical significance of these 
changes in clarithromycin plasma 
levels is not known. Alternatives 
to clarithromycin (e.g. 
azithromycin) may be considered. 
No dose adjustment is necessary 
for efavirenz.  

Other macrolide antibiotics (e.g., 
erythromycin)/Efavirenz

Interaction not studied. No data are available to make a 
dose recommendation.

Antimycobacterials
Rifabutin/Efavirenz
(300 mg once daily/600 mg once 
daily)

Rifabutin:
AUC: ↓ 38 % (↓ 28 to ↓ 47)
Cmax: ↓ 32 % (↓ 15 to ↓ 46)
Cmin: ↓ 45 % (↓ 31 to ↓ 56) 
Efavirenz:
AUC: ↔
Cmax: ↔
Cmin: ↓ 12 % (↓ 24 to ↑ 1) 
(CYP3A4 induction)

The daily dose of rifabutin should 
be increased by 50 % when 
administered with efavirenz. 
Consider doubling the rifabutin 
dose in regimens where rifabutin 
is given 2 or 3 times a week in 
combination with efavirenz. The 
clinical effect of this dose 
adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2).

Rifampicin/Efavirenz
(600 mg once daily/600 mg once 
daily)

Efavirenz:
AUC: ↓ 26 % (↓ 15 to ↓ 36)
Cmax: ↓ 20 % (↓ 11 to ↓ 28)
Cmin: ↓ 32 % (↓ 15 to ↓ 46) 
(CYP3A4 and CYP2B6 
induction)

When taken with rifampicin in 
patients weighing 50 kg or greater, 
increasing efavirenz daily dose to 
800 mg may provide exposure 
similar to a daily dose of 600 mg, 
when taken without rifampicin. 
The clinical effect of this dose 
adjustment has not been 
adequately evaluated. Individual 
tolerability and virological 
response should be considered 
when making the dose adjustment 
(see section 5.2). No dose 
adjustment is necessary for 
rifampicin, including 600 mg.

 



46

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Antifungals
Itraconazole/Efavirenz
(200 mg q12h/600 mg once daily)

Itraconazole: 
AUC: ↓ 39 % (↓ 21 to ↓ 53)
Cmax: ↓ 37 % (↓ 20 to ↓ 51)
Cmin: ↓ 44 % (↓ 27 to ↓ 58) 
(decrease in itraconazole 
concentrations: CYP3A4 
induction)
Hydroxyitraconazole:
AUC: ↓ 37 % (↓ 14 to ↓ 55) 
Cmax: ↓ 35 % (↓ 12 to ↓ 52) 
Cmin: ↓ 43 % (↓ 18 to ↓ 60) 
Efavirenz: 
No clinically significant 
pharmacokinetic change.  

Since no dose recommendation for 
itraconazole can be made, 
alternative antifungal treatment 
should be considered.

Posaconazole/Efavirenz
--/400 mg once daily

Posaconazole:
AUC: ↓ 50 % 

Cmax: ↓ 45 %
(UDP-G induction)

Concomitant use of posaconazole 
and efavirenz should be avoided 
unless the benefit to the patient 
outweighs the risk.

Voriconazole/Efavirenz
(200 mg twice daily/400 mg once 
daily)

Voriconazole/Efavirenz
(400 mg twice daily/300 mg once 
daily)

Voriconazole:
AUC: ↓ 77 %
Cmax: ↓ 61 %
Efavirenz:
AUC: ↑ 44 %
Cmax: ↑ 38 %
Voriconazole:
AUC: ↓ 7 % (↓ 23 to ↑ 13) *
Cmax: ↑ 23 % (↓ 1 to ↑ 53) *
Efavirenz:
AUC: ↑ 17 % (↑ 6 to ↑ 29) **
Cmax: ↔**
*compared to 200 mg twice daily 
alone
** compared to 600 mg once 
daily alone
(competitive inhibition of 
oxidative metabolism)

When efavirenz is co-administered 
with voriconazole, the 
voriconazole maintenance dose 
must be increased to 400 mg twice 
daily and the efavirenz dose must 
be reduced by 50 %, i.e., to 
300 mg once daily. When 
treatment with voriconazole is 
stopped, the initial dose of 
efavirenz should be restored.

Fluconazole/Efavirenz
(200 mg once daily/400 mg once 
daily)

No clinically significant 
pharmacokinetic interaction

No dose adjustment is necessary 
for either medicinal product.

Ketoconazole and other imidazole 
antifungals

Interaction not studied No data are available to make a 
dose recommendation.

Antimalarials
Artemether/lumefantrine/
Efavirenz
(20/120 mg tablet, 6 doses of 4 
tablets each over 3 days/600 mg once 
daily)

Artemether:
AUC: ↓ 51% 
Cmax: ↓ 21% 
Dihydroartemisinin:
AUC: ↓ 46%
Cmax: ↓ 38% 
Lumefantrine:
AUC: ↓ 21% 
Cmax: ↔
Efavirenz:
AUC: ↓ 17%
Cmax: ↔
(CYP3A4 induction)

Since decreased concentrations of 
artemether, dihydroartemisinin, or 
lumefantrine may result in a 
decrease of antimalarial efficacy, 
caution is recommended when 
efavirenz and 
artemether/lumefantrine tablets are 
coadministered.

 



47

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Atovaquone and proguanil 
hydrochloride/Efavirenz
(250/100 mg single dose/600 mg 
once daily)

Atovaquone:
AUC: ↓ 75% (↓ 62 to ↓ 84)

Cmax: ↓ 44% (↓ 20 to ↓ 61)

Proguanil:
AUC: ↓ 43% (↓ 7 to ↓ 65)
Cmax: ↔

Concomitant administration of 
atovaquone/proguanil with 
efavirenz should be avoided.

ACID REDUCING AGENTS
Aluminium hydroxide-magnesium 
hydroxide-simethicone 
antacid/Efavirenz
(30 mL single dose/400 mg single 
dose)
Famotidine/Efavirenz
(40 mg single dose/400 mg single 
dose)

Neither aluminium/magnesium 
hydroxide antacids nor famotidine 
altered the absorption of 
efavirenz.  

Co-administration of efavirenz 
with medicinal products that alter 
gastric pH would not be expected 
to affect efavirenz absorption.

ANTIANXIETY AGENTS
Lorazepam/Efavirenz
(2 mg single dose/600 mg once daily)

Lorazepam: 
AUC: ↑ 7 % (↑ 1 to ↑ 14)
Cmax: ↑ 16 % (↑ 2 to ↑ 32)
These changes are not considered 
clinically significant.  

No dose adjustment is necessary 
for either medicinal product.

ANTICOAGULANTS
Warfarin/Efavirenz
Acenocoumarol/Efavirenz

Interaction not studied. Plasma 
concentrations and effects of 
warfarin or acenocoumarol are 
potentially increased or decreased 
by efavirenz.

Dose adjustment of warfarin or 
acenocoumarol may be required.

ANTICONVULSANTS
Carbamazepine/Efavirenz
(400 mg once daily/600 mg once 
daily)

Carbamazepine:
AUC: ↓ 27 % (↓ 20 to ↓ 33)
Cmax: ↓ 20 % (↓ 15 to ↓ 24)
Cmin: ↓ 35 % (↓ 24 to ↓ 44)
Efavirenz:
AUC: ↓ 36 % (↓ 32 to ↓ 40)
Cmax: ↓ 21 % (↓ 15 to ↓ 26)
Cmin: ↓ 47 % (↓ 41 to ↓ 53)
(decrease in carbamazepine 
concentrations: CYP3A4 
induction; decrease in efavirenz 
concentrations: CYP3A4 and 
CYP2B6 induction) 
The steady-state AUC, Cmax and 
Cmin of the active carbamazepine 
epoxide metabolite remained 
unchanged. Co-administration of 
higher doses of either efavirenz or 
carbamazepine has not been 
studied.

No dose recommendation can be 
made. An alternative 
anticonvulsant should be 
considered. Carbamazepine 
plasma levels should be monitored 
periodically.

 



48

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Phenytoin, Phenobarbital, and other 
anticonvulsants that are substrates of 
CYP450 isoenzymes

Interaction not studied. There is a 
potential for reduction or increase 
in the plasma concentrations of 
phenytoin, phenobarbital and 
other anticonvulsants that are 
substrates of CYP450 isoenzymes 
when co-administered with 
efavirenz.

When efavirenz is co-administered 
with an anticonvulsant that is a 
substrate of CYP450 isoenzymes, 
periodic monitoring of 
anticonvulsant levels should be 
conducted.

Valproic acid/Efavirenz
(250 mg twice daily/600 mg once 
daily)

No clinically significant effect on 
efavirenz pharmacokinetics. 
Limited data suggest there is no 
clinically significant effect on 
valproic acid pharmacokinetics.

No dose adjustment is necessary 
for efavirenz. Patients should be 
monitored for seizure control.

Vigabatrin/Efavirenz
Gabapentin/Efavirenz

Interaction not studied. Clinically 
significant interactions are not 
expected since vigabatrin and 
gabapentin are exclusively 
eliminated unchanged in the urine 
and are unlikely to compete for 
the same metabolic enzymes and 
elimination pathways as 
efavirenz.

No dose adjustment is necessary 
for any of these medicinal 
products.

ANTIDEPRESSANTS
Selective Serotonin Reuptake Inhibitors (SSRIs)
Sertraline/Efavirenz
(50 mg once daily/600 mg once daily)

Sertraline:
AUC: ↓ 39 % (↓ 27 to ↓ 50) 
Cmax: ↓ 29 % (↓ 15 to ↓ 40) 
Cmin: ↓ 46 % (↓ 31 to ↓ 58)
Efavirenz: 
AUC: ↔
Cmax: ↑ 11 % (↑ 6 to ↑ 16)
Cmin: ↔ 
(CYP3A4 induction)

Sertraline dose increases should be 
guided by clinical response.
No dose adjustment is necessary 
for efavirenz.

Paroxetine/Efavirenz
(20 mg once daily/600 mg once daily)

No clinically significant 
pharmacokinetic interaction

No dose adjustment is necessary 
for either medicinal product.

Fluoxetine/Efavirenz Interaction not studied. Since 
fluoxetine shares a similar 
metabolic profile with paroxetine, 
i.e. a strong CYP2D6 inhibitory 
effect, a similar lack of interaction 
would be expected for fluoxetine.

No dose adjustment is necessary 
for either medicinal product.

Norepinephrine and dopamine reuptake inhibitor
Bupropion/Efavirenz
[150 mg single dose (sustained 
release)/600 mg once daily]

Bupropion:

AUC: ↓ 55% (↓ 48 to ↓ 62) 

Cmax: ↓ 34% (↓ 21 to ↓ 47) 
Hydroxybupropion: 
AUC: ↔
Cmax: ↑ 50% (↑ 20 to ↑ 80)
(CYP2B6 induction)

Increases in bupropion dosage 
should be guided by clinical 
response, but the maximum 
recommended dose of bupropion 
should not be exceeded. No dose 
adjustment is necessary for 
efavirenz.

 



49

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

ANTIHISTAMINES
Cetirizine/Efavirenz
(10 mg single dose/600 mg once 
daily)

Cetirizine:
AUC: ↔
Cmax: ↓ 24 % (↓ 18 to ↓ 30)
These changes are not considered 
clinically significant.
Efavirenz: 
No clinically significant 
pharmacokinetic interaction.

No dose adjustment is necessary 
for either medicinal product.

CARDIOVASCULAR AGENTS
Calcium Channel Blockers  
Diltiazem/Efavirenz
(240 mg once daily/600 mg once 
daily)

Diltiazem:
AUC: ↓ 69 % (↓ 55 to ↓ 79) 
Cmax: ↓ 60 % (↓ 50 to ↓ 68) 
Cmin: ↓ 63 % (↓ 44 to ↓ 75)
Desacetyl diltiazem:
AUC: ↓ 75 % (↓ 59 to ↓ 84) 
Cmax: ↓ 64 % (↓ 57 to ↓ 69) 
Cmin: ↓ 62 % (↓ 44 to ↓ 75)
N-monodesmethyl diltiazem:
AUC: ↓ 37 % (↓ 17 to ↓ 52)
Cmax: ↓ 28 % (↓ 7 to ↓ 44)
Cmin: ↓ 37 % (↓ 17 to ↓ 52)
Efavirenz:
AUC: ↑ 11 % (↑ 5 to ↑ 18)
Cmax: ↑ 16 % (↑ 6 to ↑ 26) 
Cmin: ↑ 13 % (↑ 1 to ↑ 26)
(CYP3A4 induction)
The increase in efavirenz 
pharmacokinetic parameters is 
not considered clinically 
significant.

Dose adjustments of diltiazem 
should be guided by clinical 
response (refer to the Summary of 
Product Characteristics for 
diltiazem). No dose adjustment is 
necessary for efavirenz.

Verapamil, Felodipine, Nifedipine 
and Nicardipine

Interaction not studied. When
efavirenz is co-administered with 
a calcium channel blocker that is a 
substrate of the CYP3A4 enzyme, 
there is a potential for reduction in 
the plasma concentrations of the 
calcium channel blocker.

Dose adjustments of calcium 
channel blockers should be guided 
by clinical response (refer to the 
Summary of Product 
Characteristics for the calcium 
channel blocker).

LIPID LOWERING MEDICINAL PRODUCTS

HMG Co-A Reductase Inhibitors
Atorvastatin/Efavirenz
(10 mg once daily/600 mg once daily)

Atorvastatin:
AUC: ↓ 43 % (↓ 34 to ↓ 50)
Cmax: ↓ 12 % (↓ 1 to ↓ 26)
2-hydroxy atorvastatin:
AUC: ↓ 35 % (↓ 13 to ↓ 40)
Cmax: ↓ 13 % (↓ 0 to ↓ 23)
4-hydroxy atorvastatin:
AUC: ↓ 4 % (↓ 0 to ↓ 31)
Cmax: ↓ 47 % (↓ 9 to ↓ 51)
Total active HMG Co-A reductase 
inhibitors: 
AUC: ↓ 34 % (↓ 21 to ↓ 41)
Cmax: ↓ 20 % (↓ 2 to ↓ 26)

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of atorvastatin may be 
required (refer to the Summary of 
Product Characteristics for the 
atorvastatin). No dose adjustment 
is necessary for efavirenz.

 



50

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Pravastatin/Efavirenz
(40 mg once daily/600 mg once daily)

Pravastatin:
AUC: ↓ 40 % (↓ 26 to ↓ 57)
Cmax: ↓ 18 % (↓ 59 to ↑ 12)

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of pravastatin may be 
required (refer to the Summary of 
Product Characteristics for 
pravastatin). No dose adjustment 
is necessary for efavirenz.

Simvastatin/Efavirenz
(40 mg once daily/600 mg once daily)

Simvastatin:
AUC: ↓ 69 % (↓ 62 to ↓ 73)
Cmax: ↓ 76 % (↓ 63 to ↓ 79)
Simvastatin acid:
AUC: ↓ 58 % (↓ 39 to ↓ 68)
Cmax: ↓ 51 % (↓ 32 to ↓ 58)
Total active HMG Co-A reductase 
inhibitors:
AUC: ↓ 60 % (↓ 52 to ↓ 68)
Cmax: ↓ 62 % (↓ 55 to ↓ 78)
(CYP3A4 induction)
Co-administration of efavirenz 
with atorvastatin, pravastatin, or 
simvastatin did not affect 
efavirenz AUC or Cmax values.

Cholesterol levels should be 
periodically monitored. Dose 
adjustments of simvastatin may be 
required (refer to the Summary of 
Product Characteristics for 
simvastatin). No dose adjustment 
is necessary for efavirenz.

Rosuvastatin/Efavirenz Interaction not studied. 
Rosuvastatin is largely excreted 
unchanged via the faeces, 
therefore interaction with 
efavirenz is not expected.

No dose adjustment is necessary 
for either medicinal product.

HORMONAL CONTRACEPTIVES
Oral:
Ethinyloestradiol+Norgestimate/ 
Efavirenz
(0.035 mg+0.25 mg once 
daily/600 mg once daily)

Ethinyloestradiol:
AUC: ↔
Cmax: ↔
Cmin: ↓ 8 % (↑ 14 to ↓ 25)
Norelgestromin (active 
metabolite):
AUC: ↓ 64 % (↓ 62 to ↓ 67)
Cmax: ↓ 46 % (↓ 39 to ↓ 52)
Cmin: ↓ 82 % (↓ 79 to ↓ 85)
Levonorgestrel (active 
metabolite):
AUC: ↓ 83 % (↓ 79 to ↓ 87)
Cmax: ↓ 80 % (↓ 77 to ↓ 83)
Cmin: ↓ 86 % (↓ 80 to ↓ 90)
(induction of metabolism)
Efavirenz: no clinically 
significant interaction.
The clinical significance of these 
effects is not known.

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6).

 



51

Medicinal product by therapeutic 
areas
(dose)

Effects on drug levels
Mean percent change in AUC, 

Cmax, Cmin with confidence 
intervals if availablea

(mechanism)

Recommendation concerning 
co-administration with efavirenz

Injection: Depo-medroxyprogesterone 
acetate (DMPA)/Efavirenz
(150 mg IM single dose DMPA)

In a 3-month drug interaction 
study, no significant differences 
in MPA pharmacokinetic 
parameters were found between 
subjects receiving efavirenz-
containing antiretroviral therapy 
and subjects receiving no 
antiretroviral therapy. Similar 
results were found by other 
investigators, although the MPA 
plasma levels were more variable 
in the second study. In both 
studies, plasma progesterone 
levels for subjects receiving 
efavirenz and DMPA remained 
low consistent with suppression 
of ovulation.

Because of the limited information 
available, a reliable method of 
barrier contraception must be used 
in addition to hormonal 
contraceptives (see section 4.6).

Implant: Etonogestrel/Efavirenz Decreased exposure of 
etonogestrel may be expected 
(CYP3A4 induction). There have 
been occasional postmarketing 
reports of contraceptive failure 
with etonogestrel in efavirenz-
exposed patients.

A reliable method of barrier 
contraception must be used in 
addition to hormonal 
contraceptives (see section 4.6).

IMMUNOSUPPRESSANTS
Immunosuppressants metabolized by 
CYP3A4 (e.g., cyclosporine, 
tacrolimus, sirolimus)/Efavirenz

Interaction not studied. Decreased 
exposure of the 
immunosuppressant may be 
expected (CYP3A4 induction). 
These immunosuppressants are 
not anticipated to affect exposure 
of efavirenz.

Dose adjustments of the 
immunosuppressant may be 
required. Close monitoring of 
immunosuppressant 
concentrations for at least 2 weeks 
(until stable concentrations are 
reached) is recommended when 
starting or stopping treatment with 
efavirenz.

OPIOIDS
Methadone/Efavirenz
(stable maintenance, 35-100 mg once 
daily/600 mg once daily)

Methadone:
AUC: ↓ 52 % (↓ 33 to ↓ 66)
Cmax: ↓ 45 % (↓ 25 to ↓ 59)
(CYP3A4 induction)
In a study of HIV infected 
intravenous drug users, 
co-administration of efavirenz 
with methadone resulted in 
decreased plasma levels of 
methadone and signs of opiate 
withdrawal. The methadone dose 
was increased by a mean of 22 % 
to alleviate withdrawal symptoms.

Concomitant administration with 
efavirenz should be avoided due to 
the risk for QTc prolongation (see 
section 4.3).

Buprenorphine/naloxone/Efavirenz Buprenorphine:
AUC: ↓ 50 %
Norbuprenorphine:
AUC: ↓ 71 %
Efavirenz:
No clinically significant 
pharmacokinetic interaction

Despite the decrease in 
buprenorphine exposure, no 
patients exhibited withdrawal 
symptoms. Dose adjustment of 
buprenorphine or efavirenz may 
not be necessary when 
co-administered.

a 90 % confidence intervals unless otherwise noted.
b 95 % confidence intervals.

 



52

Other interactions: efavirenz does not bind to cannabinoid receptors. False-positive urine cannabinoid 
test results have been reported with some screening assays in uninfected and HIV-infected subjects 
receiving efavirenz. Confirmatory testing by a more specific method such as gas 
chromatography/mass spectrometry is recommended in such cases.

4.6 Fertility, pregnancy and lactation

Contraception in males and females

Barrier contraception should always be used in combination with other methods of contraception (for 
example, oral or other hormonal contraceptives, see section 4.5). Because of the long half-life of 
efavirenz, use of adequate contraceptive measures for 12 weeks after discontinuation of efavirenz is 
recommended.

Pregnancy

Efavirenz should not be used during pregnancy, unless the patient’s clinical condition requires such 
treatment. Women of childbearing potential should undergo pregnancy testing before initiation of 
efavirenz (see section 5.3).

There have been seven retrospective reports of findings consistent with neural tube defects, including 
meningomyelocele, all in mothers exposed to efavirenz-containing regimens (excluding any 
efavirenz-containing fixed-dose combination tablets) in the first trimester. Two additional cases 
(1 prospective and 1 retrospective) including events consistent with neural tube defects have been 
reported with a fixed-dose combination tablet containing efavirenz, emtricitabine, and tenofovir 
disoproxil. A causal relationship of these events to the use of efavirenz has not been established, and 
the denominator is unknown. As neural tube defects occur within the first 4 weeks of foetal 
development (at which time neural tubes are sealed), this potential risk would concern women exposed 
to efavirenz during the first trimester of pregnancy.

As of July 2013, the Antiretroviral Pregnancy Registry (APR) has received prospective reports of 
904 pregnancies with first trimester exposure to efavirenz-containing regimens, resulting in 766 live 
births. One child was reported to have a neural tube defect, and the frequency and pattern of other 
birth defects were similar to those seen in children exposed to non-efavirenz-containing regimens, as 
well as those in HIV negative controls. The incidence of neural tube defects in the general population 
ranges from 0.5-1 case per 1,000 live births.

Malformations have been observed in foetuses from efavirenz-treated monkeys (see section 5.3).

Breast-feeding

Efavirenz has been shown to be excreted in human milk. There is insufficient information on the 
effects of efavirenz in newborns/infants. Risk to the infant can not be excluded. Breast-feeding should 
be discontinued during treatment with efavirenz. It is recommended that HIV infected women do not 
breast-feed their infants under any circumstances in order to avoid transmission of HIV.

Fertility

The effect of efavirenz on male and female fertility in rats has only been evaluated at doses that 
achieved systemic drug exposures equivalent to or below those achieved in humans given 
recommended doses of efavirenz. In these studies, efavirenz did not impair mating or fertility of male 
or female rats (doses up to 100 mg/kg/bid), and did not affect sperm or offspring of treated male rats 
(doses up to 200 mg/bid). The reproductive performance of offspring born to female rats given 
efavirenz was not affected.

 



53

4.7 Effects on ability to drive and use machines

Efavirenz may cause dizziness, impaired concentration, and/or somnolence. Patients should be 
instructed that if they experience these symptoms they should avoid potentially hazardous tasks such 
as driving or operating machinery.

4.8 Undesirable effects

Summary of the safety profile

Efavirenz has been studied in over 9,000 patients. In a subset of 1,008 adult patients who received 
600 mg efavirenz daily in combination with PIs and/or NRTIs in controlled clinical studies, the most 
frequently reported adverse reactions of at least moderate severity reported in at least 5 % of patients 
were rash (11.6 %), dizziness (8.5 %), nausea (8.0 %), headache (5.7 %) and fatigue (5.5 %). The most 
notable adverse reactions associated with efavirenz are rash and nervous system symptoms. Nervous 
system symptoms usually begin soon after therapy onset and generally resolve after the first 2 - 4 
weeks. Severe skin reactions such as Stevens-Johnson syndrome and erythema multiforme; psychiatric 
adverse reactions including severe depression, death by suicide, and psychosis like behaviour; and 
seizures have been reported in patients treated with efavirenz. The administration of efavirenz with 
food may increase efavirenz exposure and may lead to an increase in the frequency of adverse 
reactions (see section 4.4).

The long-term safety profile of efavirenz-containing regimens was evaluated in a controlled trial (006) 
in which patients received efavirenz + zidovudine + lamivudine (n = 412, median duration 
180 weeks), efavirenz + indinavir (n = 415, median duration 102 weeks), or indinavir + zidovudine + 
lamivudine (n = 401, median duration 76 weeks). Long-term use of efavirenz in this study was not 
associated with any new safety concerns.

Tabulated list of adverse reactions

Adverse reactions of moderate or greater severity with at least possible relationship to treatment 
regimen (based on investigator attribution) reported in clinical trials of efavirenz at the recommended 
dose in combination therapy (n = 1,008) are listed below. Also listed in italics are adverse reactions 
observed post-marketing in association with efavirenz-containing antiretroviral treatment regimens. 
Frequency is defined using the following convention: very common (≥ 1/10); common (≥ 1/100, 
< 1/10); uncommon (≥ 1/1,000, < 1/100); rare (≥ 1/10,000, < 1/1,000); or very rare (< 1/10,000).

 



54

Immune system disorders
uncommon hypersensitivity

Metabolism and nutrition disorders
common hypertriglyceridaemia*

uncommon hypercholesterolaemia*

Psychiatric disorders
common abnormal dreams, anxiety, depression, insomnia*

uncommon affect lability, aggression, confusional state, 
euphoric mood, hallucination, mania, paranoia, 
psychosis‡, suicide attempt, suicide ideation, 
catatonia*

rare delusion‡‡, neurosis‡‡, completed suicide‡‡*

Nervous system disorders
common cerebellar coordination and balance 

disturbances‡, disturbance in attention (3.6 %), 
dizziness (8.5 %), headache (5.7 %), somnolence 
(2.0 %)*

uncommon agitation, amnesia, ataxia, coordination abnormal, 
convulsions, thinking abnormal, tremor‡

Eye disorders
uncommon vision blurred

Ear and labyrinth disorders
uncommon tinnitus‡, vertigo

Vascular disorders
uncommon flushing‡

Gastrointestinal disorders
common abdominal pain, diarrhoea, nausea, vomiting

uncommon pancreatitis 

Hepatobiliary disorders
common aspartate aminotransferase (AST) increased*, 

alanine aminotransferase (ALT) increased*, 
gamma-glutamyltransferase (GGT) increased*

uncommon hepatitis acute

rare hepatic failure‡‡*

 



55

Skin and subcutaneous tissue disorders
very common rash (11.6 %)*

common pruritus

uncommon erythema multiforme, Stevens-Johnson 
syndrome*

rare photoallergic dermatitis‡

Reproductive system and breast disorders
uncommon gynaecomastia

General disorders and administration site conditions
common fatigue

*,‡ ,‡‡ See section Description of selected adverse reactions for more details.

Description of selected adverse reactions

Information regarding post-marketing surveillance
‡ These adverse reactions were identified through post-marketing surveillance; however, the 
frequencies were determined using data from 16 clinical trials (n=3,969). 

‡‡These adverse reactions were identified through post-marketing surveillance but not reported as 
drug-related events for efavirenz-treated patients in 16 clinical trials. The frequency category of "rare" 
was defined per A Guideline on Summary of Product Characteristics (SmPC) (rev. 2, Sept 2009) on 
the basis of an estimated upper bound of the 95% confidence interval for 0 events given the number of 
patients treated with efavirenz in these clinical trials (n=3,969).

Rash
In clinical studies, 26 % of patients treated with 600 mg of efavirenz experienced skin rash compared 
with 17 % of patients treated in control groups. Skin rash was considered treatment related in 18 % of 
patients treated with efavirenz. Severe rash occurred in less than 1 % of patients treated with efavirenz, 
and 1.7 % discontinued therapy because of rash. The incidence of erythema multiforme or 
Stevens-Johnson syndrome was approximately 0.1 %.

Rashes are usually mild-to-moderate maculopapular skin eruptions that occur within the first two 
weeks of initiating therapy with efavirenz. In most patients rash resolves with continuing therapy with 
efavirenz within one month. Efavirenz can be reinitiated in patients interrupting therapy because of 
rash. Use of appropriate antihistamines and/or corticosteroids is recommended when efavirenz is 
restarted.

Experience with efavirenz in patients who discontinued other antiretroviral agents of the NNRTI class 
is limited. Reported rates of recurrent rash following a switch from nevirapine to efavirenz therapy, 
primarily based on retrospective cohort data from published literature, range from 13 to 18 %, 
comparable to the rate observed in patients treated with efavirenz in clinical studies. (See section 4.4.)

 



56

Psychiatric symptoms
Serious psychiatric adverse reactions have been reported in patients treated with efavirenz. In 
controlled trials the frequency of specific serious psychiatric events were: 

Efavirenz regimen
(n=1,008)

Control regimen
(n=635)

- severe depression 1.6 % 0.6 %
- suicidal ideation 0.6 % 0.3 %
- non-fatal suicide attempts 0.4 % 0 %
- aggressive behaviour 0.4 % 0.3 %
- paranoid reactions 0.4 % 0.3 %
- manic reactions 0.1 % 0 %

Patients with a history of psychiatric disorders appear to be at greater risk of these serious psychiatric 
adverse reactions with frequencies of each of the above events ranging from 0.3 % for manic reactions 
to 2.0 % for both severe depression and suicidal ideation. There have also been post-marketing reports 
of death by suicide, delusions, psychosis-like behaviour and catatonia.

Nervous system symptoms
In clinical controlled trials, frequently reported adverse reactions included, but were not limited to: 
dizziness, insomnia, somnolence, impaired concentration and abnormal dreaming. Nervous system 
symptoms of moderate-to-severe intensity were experienced by 19 % (severe 2.0 %) of patients 
compared to 9 % (severe 1 %) of patients receiving control regimens. In clinical studies 2 % of 
patients treated with efavirenz discontinued therapy due to such symptoms.

Nervous system symptoms usually begin during the first one or two days of therapy and generally 
resolve after the first 2 - 4 weeks. In a study of uninfected volunteers, a representative nervous system 
symptom had a median time to onset of 1 hour post-dose and a median duration of 3 hours. Nervous 
system symptoms may occur more frequently when efavirenz is taken concomitantly with meals 
possibly due to increased efavirenz plasma levels (see section 5.2). Dosing at bedtime seems to 
improve the tolerability of these symptoms and can be recommended during the first weeks of therapy 
and in patients who continue to experience these symptoms (see section 4.2). Dose reduction or 
splitting the daily dose has not been shown to provide benefit.

Analysis of long-term data showed that, beyond 24 weeks of therapy, the incidences of new-onset 
nervous system symptoms among efavirenz-treated patients were generally similar to those in the 
control arm.

Hepatic failure
A few of the postmarketing reports of hepatic failure, including cases in patients with no pre-existing 
hepatic disease or other identifiable risk factors, were characterized by a fulminant course, progressing 
in some cases to transplantation or death.

Immune Reactivation Syndrome
In HIV infected patients with severe immune deficiency at the time of initiation of combination 
antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or residual opportunistic 
infections may arise. Autoimmune disorders (such as Graves’ disease and autoimmune hepatitis) have 
also been reported; however, the reported time to onset is more variable and these events can occur 
many months after initiation of treatment (see section 4.4).

Osteonecrosis
Cases of osteonecrosis have been reported, particularly in patients with generally acknowledged risk 
factors, advanced HIV disease or long-term exposure to combination antiretroviral therapy (CART). 
The frequency of this is unknown (see section 4.4).

 



57

Laboratory test abnormalities
Liver enzymes: elevations of AST and ALT to greater than five times the upper limit of the normal 
range (ULN) were seen in 3 % of 1,008 patients treated with 600 mg of efavirenz (5-8 % after 
long-term treatment in study 006). Similar elevations were seen in patients treated with control 
regimens (5 % after long-term treatment). Elevations of GGT to greater than five times ULN were 
observed in 4 % of all patients treated with 600 mg of efavirenz and 1.5 - 2 % of patients treated with 
control regimens (7 % of efavirenz-treated patients and 3 % of control-treated patients after long-term 
treatment). Isolated elevations of GGT in patients receiving efavirenz may reflect enzyme induction.
In the long-term study (006), 1 % of patients in each treatment arm discontinued because of liver or 
biliary system disorders.

Amylase: in the clinical trial subset of 1,008 patients, asymptomatic increases in serum amylase levels 
greater than 1.5 times the upper limit of normal were seen in 10 % of patients treated with efavirenz 
and 6 % of patients treated with control regimens. The clinical significance of asymptomatic increases 
in serum amylase is unknown.

Metabolic parameters
Weight and levels of blood lipids and glucose may increase during antiretroviral therapy (see 
section 4.4).

Paediatric population

Undesirable effects in children were generally similar to those of adult patients. Rash was reported 
more frequently in children (in a clinical study including 57 children who received efavirenz during a 
48-week period, rash was reported in 46 %) and was more often of higher grade than in adults (severe 
rash was reported in 5.3 % of children). Prophylaxis with appropriate antihistamines prior to initiating 
therapy with efavirenz in children may be considered. Although nervous system symptoms are 
difficult for young children to report, they appear to be less frequent in children and were generally 
mild. In the study of 57 children, 3.5 % of patients experienced nervous system symptoms of moderate 
intensity, predominantly dizziness. No child had severe symptoms or had to discontinue because of 
nervous system symptoms.

Other special populations

Liver enzymes in hepatitis B or C co-infected patients
In the long-term data set from study 006, 137 patients treated with efavirenz-containing regimens 
(median duration of therapy, 68 weeks) and 84 treated with a control regimen (median duration, 
56 weeks) were seropositive at screening for hepatitis B (surface antigen positive) and/or C (hepatitis 
C antibody positive). Among co-infected patients in study 006, elevations in AST to greater than five 
times ULN developed in 13 % of efavirenz treated patients and in 7 % of controls, and elevations in 
ALT to greater than five times ULN developed in 20 % and 7 % respectively. Among co-infected 
patients, 3 % of those treated with efavirenz and 2 % in the control arm discontinued because of liver 
disorders (see section 4.4).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V.

4.9 Overdose

Some patients accidentally taking 600 mg twice daily have reported increased nervous system 
symptoms. One patient experienced involuntary muscle contractions.

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


58

Treatment of overdose with efavirenz should consist of general supportive measures, including 
monitoring of vital signs and observation of the patient’s clinical status. Administration of activated 
charcoal may be used to aid removal of unabsorbed efavirenz. There is no specific antidote for 
overdose with efavirenz. Since efavirenz is highly protein bound, dialysis is unlikely to remove 
significant quantities of it from blood.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antivirals for systemic use. Non-nucleoside reverse transcriptase 
inhibitors. ATC code: J05A G03

Mechanism of action

Efavirenz is a NNRTI of HIV-1. Efavirenz is a non-competitive inhibitor of HIV-1 reverse 
transcriptase (RT) and does not significantly inhibit HIV-2 RT or cellular DNA polymerases (, , 
or ).

Cardiac Electrophysiology

The effect of efavirenz on the QTc interval was evaluated in an open-label, positive and placebo 
controlled, fixed single sequence 3-period, 3-treatment crossover QT study in 58 healthy subjects 
enriched for CYP2B6 polymorphisms. The mean Cmax of efavirenz in subjects with CYP2B6 *6/*6 
genotype following the administration of 600 mg daily dose for 14 days was 2.25-fold the mean Cmax
observed in subjects with CYP2B6 *1/*1 genotype. A positive relationship between efavirenz 
concentration and QTc prolongation was observed. Based on the concentration-QTc relationship, the 
mean QTc prolongation and its upper bound 90% confidence interval are 8.7 ms and 11.3 ms in 
subjects with CYP2B6*6/*6 genotype following the administration of 600 mg daily dose for 14 days 
(see section 4.5).

Antiviral activity

The free concentration of efavirenz required for 90 to 95 % inhibition of wild type or 
zidovudine-resistant laboratory and clinical isolates in vitro ranged from 0.46 to 6.8 nM in 
lymphoblastoid cell lines, peripheral blood mononuclear cells (PBMCs) and macrophage/monocyte 
cultures.

Resistance

The potency of efavirenz in cell culture against viral variants with amino acid substitutions at positions 
48, 108, 179, 181 or 236 in RT or variants with amino acid substitutions in the protease was similar to 
that observed against wild type viral strains. The single substitutions which led to the highest 
resistance to efavirenz in cell culture correspond to a leucine-to-isoleucine change at position 100 
(L100I, 17 to 22-fold resistance) and a lysine-to-asparagine at position 103 (K103N, 18 to 33-fold 
resistance). Greater than 100-fold loss of susceptibility was observed against HIV variants expressing 
K103N in addition to other amino acid substitutions in RT.

K103N was the most frequently observed RT substitution in viral isolates from patients who 
experienced a significant rebound in viral load during clinical studies of efavirenz in combination with 
indinavir or zidovudine + lamivudine. This mutation was observed in 90 % of patients receiving 
efavirenz with virological failure. Substitutions at RT positions 98, 100, 101, 108, 138, 188, 190 or 
225 were also observed, but at lower frequencies, and often only in combination with K103N. The 
pattern of amino acid substitutions in RT associated with resistance to efavirenz was independent of 
the other antiviral medicinal products used in combination with efavirenz.

 



59

Cross-resistance

Cross resistance profiles for efavirenz, nevirapine and delavirdine in cell culture demonstrated that the 
K103N substitution confers loss of susceptibility to all three NNRTIs. Two of three 
delavirdine-resistant clinical isolates examined were cross-resistant to efavirenz and contained the 
K103N substitution. A third isolate which carried a substitution at position 236 of RT was not 
cross-resistant to efavirenz.

Viral isolates recovered from PBMCs of patients enrolled in efavirenz clinical studies who showed 
evidence of treatment failure (viral load rebound) were assessed for susceptibility to NNRTIs. Thirteen 
isolates previously characterised as efavirenz-resistant were also resistant to nevirapine and 
delavirdine. Five of these NNRTI-resistant isolates were found to have K103N or a 
valine-to-isoleucine substitution at position 108 (V108I) in RT. Three of the efavirenz treatment 
failure isolates tested remained sensitive to efavirenz in cell culture and were also sensitive to 
nevirapine and delavirdine.

The potential for cross resistance between efavirenz and PIs is low because of the different enzyme 
targets involved. The potential for cross-resistance between efavirenz and NRTIs is low because of the 
different binding sites on the target and mechanism of action.

Clinical efficacy

Efavirenz has not been studied in controlled studies in patients with advanced HIV disease, namely 
with CD4 counts < 50 cells/mm3, or in PI or NNRTI experienced patients. Clinical experience in 
controlled studies with combinations including didanosine or zalcitabine is limited.

Two controlled studies (006 and ACTG 364) of approximately one year duration with efavirenz in 
combination with NRTIs and/or PIs, have demonstrated reduction of viral load below the limit of 
quantification of the assay and increased CD4 lymphocytes in antiretroviral therapy-naïve and 
NRTI-experienced HIV-infected patients. Study 020 showed similar activity in NRTI-experienced 
patients over 24 weeks. In these studies the dose of efavirenz was 600 mg once daily; the dose of 
indinavir was 1,000 mg every 8 hours when used with efavirenz and 800 mg every 8 hours when used 
without efavirenz. The dose of nelfinavir was 750 mg given three times a day. The standard doses of 
NRTIs given every 12 hours were used in each of these studies.

Study 006, a randomized, open-label trial, compared efavirenz + zidovudine + lamivudine or 
efavirenz + indinavir with indinavir + zidovudine + lamivudine in 1,266 patients who were required to 
be efavirenz-, lamivudine-, NNRTI-, and PI-naive at study entry. The mean baseline CD4 cell count 
was 341 cells/mm3 and the mean baseline HIV-RNA level was 60,250 copies/ml. Efficacy results for 
study 006 on a subset of 614 patients who had been enrolled for at least 48 weeks are found in Table 3. 
In the analysis of responder rates (the non-completer equals failure analysis [NC = F]), patients who 
terminated the study early for any reason, or who had a missing HIV-RNA measurement that was 
either preceded or followed by a measurement above the limit of assay quantification were considered 
to have HIV-RNA above 50 or above 400 copies/ml at the missing time points.

 



60

Table 3: Efficacy results for study 006

Responder rates (NC = Fa)
Plasma HIV-RNA

Mean change 
from 

baseline-CD4 
cell count

< 400 copies/ml 
(95 % C.I.b)

< 50 copies/ml 
(95 % C.I.b)

cells/mm3 

(S.E.M.c)
Treatment 
Regimend

n 48 weeks 48 weeks 48 weeks

EFV + 
ZDV + 3TC

202 67 %
(60 %, 73 %)

62 %
(55 %, 69 %)

187
(11.8)

EFV + IDV 206 54 %
(47 %, 61 %)

48 %
(41 %, 55 %)

177
(11.3)

IDV + 
ZDV + 3TC

206 45 %
(38 %, 52 %)

40 %
(34 %, 47 %)

153
(12.3)

a NC = F, noncompleter = failure.
b C.I., confidence interval.
c S.E.M., standard error of the mean.
d EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir.

Long-term results at 168 weeks of study 006 (160 patients completed study on treatment with 
EFV +IDV, 196 patients with EFV + ZDV + 3TC and 127 patients with IDV + ZDV + 3TC, 
respectively), suggest durability of response in terms of proportions of patients with HIV RNA 
< 400 copies/ml, HIV RNA < 50 copies/ml and in terms of mean change from baseline CD4 cell 
count.

Efficacy results for studies ACTG 364 and 020 are found in Table 4. Study ACTG 364 enrolled 
196 patients who had been treated with NRTIs but not with PIs or NNRTIs. Study 020 enrolled 
327 patients who had been treated with NRTIs but not with PIs or NNRTIs. Physicians were allowed 
to change their patient’s NRTI regimen upon entry into the study. Responder rates were highest in 
patients who switched NRTIs.

Table 4: Efficacy results for studies ACTG 364 and 020

Responder rates (NC = Fa)
Plasma HIV-RNA

Mean change from 
baseline-CD4 cell count

Study Number/
Treatment Regimensb

n % (95 % C.I.c) % (95 % C.I.) cells/mm3 (S.E.M.d)

Study ACTG 364
48 weeks

< 500 copies/ml < 50 copies/ml

EFV + NFV + NRTIs 65 70 (59, 82) --- --- 107 (17.9)
EFV + NRTIs 65 58 (46, 70) --- --- 114 (21.0)
NFV + NRTIs 66 30 (19, 42) --- --- 94 (13.6)

Study 020
24 weeks

< 400 copies/ml < 50 copies/ml

EFV + IDV + NRTIs 157 60 (52, 68) 49 (41, 58) 104 (9.1)
IDV + NRTIs 170 51 (43, 59) 38 (30, 45) 77 (9.9)

a NC = F, noncompleter = failure.
b EFV, efavirenz; ZDV, zidovudine; 3TC, lamivudine; IDV, indinavir; NRTI, nucleoside reverse transcriptase inhibitor; 
NFV, nelfinavir.
c C.I., confidence interval for proportion of patients in response.
d S.E.M., standard error of the mean.
---, not performed. 

 



61

Paediatric population: ACTG 382 is an ongoing uncontrolled study of 57 NRTI-experienced 
paediatric patients (3 - 16 years) which characterises the pharmacokinetics, antiviral activity and safety 
of efavirenz in combination with nelfinavir (20 - 30 mg/kg given three times a day) and one or more 
NRTIs. The starting dose of efavirenz was the equivalent of a 600 mg dose (adjusted from calculated 
body size based on weight). The response rate, based on the NC = F analysis of the percentage of 
patients with plasma HIV-RNA < 400 copies/ml at 48 weeks was 60 % (95 %, C.I. 47, 72), and 53 % 
(C.I. 40, 66) based on percentage of patients with plasma HIV-RNA < 50 copies/ml. The mean CD4 
cell counts were increased by 63  34.5 cells/mm3 from baseline. The durability of the response was 
similar to that seen in adult patients.

5.2 Pharmacokinetic properties

Absorption

Peak efavirenz plasma concentrations of 1.6 - 9.1 M were attained by 5 hours following single oral 
doses of 100 mg to 1,600 mg administered to uninfected volunteers. Dose related increases in Cmax and 
AUC were seen for doses up to 1,600 mg; the increases were less than proportional suggesting 
diminished absorption at higher doses. Time to peak plasma concentrations (3 - 5 hours) did not 
change following multiple dosing and steady-state plasma concentrations were reached in 6 - 7 days.

In HIV infected patients at steady state, mean Cmax, mean Cmin, and mean AUC were linear with 
200 mg, 400 mg, and 600 mg daily doses. In 35 patients receiving efavirenz 600 mg once daily, steady 
state Cmax was 12.9 ± 3.7 M (29 %) [mean ± S.D. (% C.V.)], steady state Cmin was 5.6 ± 3.2 M 
(57 %), and AUC was 184 ± 73 M·h (40 %).

Effect of food

The AUC and Cmax of a single 600 mg dose of efavirenz film-coated tablets in uninfected volunteers 
was increased by 28 % (90 % CI: 22 – 33 %) and 79 % (90 % CI:58 – 102 %), respectively, when 
given with a high fat meal relative to when given under fasted conditions (see section 4.4).

Distribution

Efavirenz is highly bound (approximately 99.5 - 99.75 %) to human plasma proteins, predominantly 
albumin. In HIV-1 infected patients (n = 9) who received efavirenz 200 to 600 mg once daily for at 
least one month, cerebrospinal fluid concentrations ranged from 0.26 to 1.19 % (mean 0.69 %) of the 
corresponding plasma concentration. This proportion is approximately 3-fold higher than the 
non-protein-bound (free) fraction of efavirenz in plasma.

Biotransformation

Studies in humans and in vitro studies using human liver microsomes have demonstrated that 
efavirenz is principally metabolised by the cytochrome P450 system to hydroxylated metabolites with 
subsequent glucuronidation of these hydroxylated metabolites. These metabolites are essentially 
inactive against HIV-1. The in vitro studies suggest that CYP3A4 and CYP2B6 are the major 
isozymes responsible for efavirenz metabolism and that it inhibited P450 isozymes 2C9, 2C19, and 
3A4. In in vitro studies efavirenz did not inhibit CYP2E1 and inhibited CYP2D6 and CYP1A2 only at 
concentrations well above those achieved clinically.

Efavirenz plasma exposure may be increased in patients with the homozygous G516T genetic variant 
of the CYP2B6 isoenzyme. The clinical implications of such an association are unknown; however, 
the potential for an increased frequency and severity of efavirenz-associated adverse events cannot be 
excluded.

Efavirenz has been shown to induce CYP3A4 and CYP2B6, resulting in the induction of its own 
metabolism which may be clinically relevant in some patients. In uninfected volunteers, multiple 
doses of 200 - 400 mg per day for 10 days resulted in a lower than predicted extent of accumulation 

 



62

(22 - 42 % lower) and a shorter terminal half-life compared with single dose administration (see 
below). Efavirenz has also been shown to induce UGT1A1. Exposures of raltegravir (a UGT1A1 
substrate) are reduced in the presence of efavirenz (see section 4.5, table 2).
Although in vitro data suggest that efavirenz inhibits CYP2C9 and CYP2C19, there have been 
contradictory reports of both increased and decreased exposures to substrates of these enzymes when 
coadministered with efavirenz in vivo. The net effect of co-administration is not clear.

Elimination

Efavirenz has a relatively long terminal half-life of at least 52 hours after single doses and 
40 - 55 hours after multiple doses. Approximately 14 - 34 % of a radiolabelled dose of efavirenz was 
recovered in the urine and less than 1 % of the dose was excreted in urine as unchanged efavirenz.

Hepatic impairment

In a single-dose study, half life was doubled in the single patient with severe hepatic impairment 
(Child-Pugh Class C), indicating a potential for a much greater degree of accumulation. A 
multiple-dose study showed no significant effect on efavirenz pharmacokinetics in patients with mild 
hepatic impairment (Child-Pugh Class A) compared with controls. There were insufficient data to 
determine whether moderate or severe hepatic impairment (Child-Pugh Class B or C) affects efavirenz 
pharmacokinetics.

Gender, race, elderly

Although limited data suggest that females as well as Asian and Pacific Island patients may have 
higher exposure to efavirenz, they do not appear to be less tolerant of efavirenz. Pharmacokinetic 
studies have not been performed in the elderly.

Paediatric population

In 49 paediatric patients receiving the equivalent of a 600 mg dose of efavirenz (dose adjusted from 
calculated body size based on weight), steady state Cmax was 14.1 M, steady state Cmin was 5.6 M, 
and AUC was 216 M·h. The pharmacokinetics of efavirenz in paediatric patients were similar to 
adults.

5.3 Preclinical safety data

Efavirenz was not mutagenic or clastogenic in conventional genotoxicity assays.

Efavirenz induced foetal resorptions in rats. Malformations were observed in 
3 of 20 foetuses/newborns from efavirenz-treated cynomolgus monkeys given doses resulting in 
plasma efavirenz concentrations similar to those seen in humans. Anencephaly and unilateral 
anophthalmia with secondary enlargement of the tongue were observed in one foetus, 
microophthalmia was observed in another foetus, and cleft palate was observed in a third foetus. No 
malformations were observed in foetuses from efavirenz-treated rats and rabbits.

Biliary hyperplasia was observed in cynomolgus monkeys given efavirenz for ≥ 1 year at a dose 
resulting in mean AUC values approximately 2-fold greater than those in humans given the 
recommended dose. The biliary hyperplasia regressed upon cessation of dosing. Biliary fibrosis has 
been observed in rats. Non-sustained convulsions were observed in some monkeys receiving efavirenz 
for ≥ 1 year, at doses yielding plasma AUC values 4- to 13-fold greater than those in humans given the 
recommended dose (see sections 4.4 and 4.8).

Carcinogenicity studies showed an increased incidence of hepatic and pulmonary tumours in female 
mice, but not in male mice. The mechanism of tumour formation and the potential relevance for 
humans are not known.

 



63

Carcinogenicity studies in male mice, male and female rats were negative. While the carcinogenic 
potential in humans is unknown, these data suggest that the clinical benefit of efavirenz outweighs the 
potential carcinogenic risk to humans.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

STOCRIN 600 mg film-coated tablets
Tablet core: Croscarmellose sodium, Microcrystalline cellulose, Sodium laurilsulfate, 
Hydroxypropylcellulose, Lactose monohydrate, Magnesium stearate

Film coating: Hypromellose (E464), Titanium dioxide (E171), Macrogol 400, Yellow iron oxide 
(E172), Carnauba wax

STOCRIN 50 mg film-coated tablets
Tablet core: Croscarmellose sodium, Microcrystalline cellulose, Sodium laurilsulfate, 
Hydroxypropylcellulose, Lactose monohydrate, Magnesium stearate

Film coating: Hypromellose (E464), Titanium dioxide (E171), Macrogol 400, Yellow iron oxide 
(E172), Carnauba wax

STOCRIN 200 mg film-coated tablets
Tablet core: Croscarmellose sodium, Microcrystalline cellulose, Sodium laurilsulfate, 
Hydroxypropylcellulose, Lactose monohydrate, Magnesium stearate

Film coating: Hypromellose (E464), Titanium dioxide (E171), Macrogol 400, Yellow iron oxide 
(E172), Carnauba wax

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

For bottles: 3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and content of container

STOCRIN 600 mg film-coated tablets
HDPE bottles with a child-resistant polypropylene closure. Each carton contains 1 bottle of 
30 film-coated tablets.

STOCRIN 50 mg film-coated tablets
HDPE bottles with a child-resistant polypropylene closure. Each carton contains 1 bottle of 
30 film-coated tablets.

STOCRIN 200 mg film-coated tablets
HDPE bottles with a child-resistant polypropylene closure. Each carton contains 1 bottle of 
90 film-coated tablets.

 



64

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/008
EU/1/99/111/010
EU/1/99/111/011

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation: 28 May 1999
Date of latest renewal: 23 April 2014

10. DATE OF REVISION OF THE TEXT

Detailed information on this product is available on the website of the European Medicines Agency 
http://www.ema.europa.eu.

 



65

ANNEX II

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH 
RELEASE

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY 
AND USE

C. OTHER CONDITIONS AND REQUIREMENTS OF THE 
MARKETING AUTHORISATION

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO 
THE SAFE AND EFFECTIVE USE OF THE MEDICINAL 
PRODUCT

 



66

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturer responsible for batch release 

Merck Sharp & Dohme B.V.
Waarderweg 39
PO Box 581
2003 PC Haarlem
The Netherlands

B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

Medicinal product subject to restricted medical prescription (see Annex I: Summary of Product 
Characteristics, section 4.2).

C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 
AUTHORISATION

 Periodic Safety Update Reports

The requirements for submission of periodic safety update reports for this medicinal product are set 
out in the list of Union reference dates (EURD list) provided for under Article 107c(7) of Directive 
2001/83/EC and any subsequent updates published on the European medicines web-portal.

D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 
EFFECTIVE USE OF THE MEDICINAL PRODUCT

 Risk Management plan (RMP)

The MAH shall perform the required pharmacovigilance activities and interventions detailed in the 
agreed RMP presented in Module 1.8.2 of the Marketing Authorisation and any agreed subsequent 
updates of the RMP.

An updated RMP should be submitted:
 At the request of the European Medicines Agency;
 Whenever the risk management system is modified, especially as the result of new information 

being received that may lead to a significant change to the benefit/risk profile or as the result of 
an important (pharmacovigilance or risk minimisation) milestone being reached.

 



67

ANNEX III

LABELLING AND PACKAGE LEAFLET 

 



68

A. LABELLING

 



69

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

OUTER CARTON AND LABEL TEXT FOR BOTTLE PACK

1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 30 mg/ml oral solution
efavirenz

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each ml contains: efavirenz 30 mg

3. LIST OF EXCIPIENTS

4. PHARMACEUTICAL FORM AND CONTENTS

180 ml oral solution
Oral syringe with a pushin bottleneck adapter.

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP 
Use the oral solution within one month after first opening the bottle.

9. SPECIAL STORAGE CONDITIONS

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

 



70

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/005

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Outer carton: STOCRIN 30 mg/ml

17. UNIQUE IDENTIFIED – 2D BARCODE

Outer carton: 2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIED – HUMAN READABLE DATA

Outer carton
PC:
SN:
NN:

 



71

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

OUTER CARTON AND LABEL TEXT FOR BOTTLE PACK

1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 600 mg film-coated tablets
efavirenz

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains: efavirenz 600 mg

3. LIST OF EXCIPIENTS

It contains: lactose monohydrate. 
See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



72

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/008

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Outer carton: STOCRIN 600 mg

17. UNIQUE IDENTIFIED – 2D BARCODE

Outer carton: 2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIED – HUMAN READABLE DATA

Outer carton
PC: 
SN:
NN:

 



73

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

OUTER CARTON AND LABEL TEXT FOR BOTTLE PACK

1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 50 mg film-coated tablets
efavirenz

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains: efavirenz 50 mg

3. LIST OF EXCIPIENTS

It contains: lactose monohydrate. 
See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

30 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT 
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



74

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/010

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Outer carton: STOCRIN 50 mg tablets

17. UNIQUE IDENTIFIED – 2D BARCODE

Outer carton: 2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIED – HUMAN READABLE DATA

Outer carton
PC: 
SN:
NN:

 



75

PARTICULARS TO APPEAR ON THE OUTER PACKAGING AND THE IMMEDIATE 
PACKAGING

OUTER CARTON AND LABEL TEXT FOR BOTTLE PACK

1. NAME OF THE MEDICINAL PRODUCT

STOCRIN 200 mg film-coated tablets
efavirenz

2. STATEMENT OF ACTIVE SUBSTANCE(S)

Each film-coated tablet contains: efavirenz 200 mg

3. LIST OF EXCIPIENTS

It contains: lactose monohydrate. 
See package leaflet for further information.

4. PHARMACEUTICAL FORM AND CONTENTS

90 film-coated tablets

5. METHOD AND ROUTE(S) OF ADMINISTRATION

Read the package leaflet before use.
Oral use.

6. SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE SIGHT AND REACH OF CHILDREN

Keep out of the sight and reach of children.

7. OTHER SPECIAL WARNING(S), IF NECESSARY

8. EXPIRY DATE

EXP

9. SPECIAL STORAGE CONDITIONS

 



76

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS 
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF 
APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Merck Sharp & Dohme B.V.
Waarderweg 39
2031 BN Haarlem
The Netherlands

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/99/111/011

13. BATCH NUMBER

Lot

14. GENERAL CLASSIFICATION FOR SUPPLY

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

Outer carton: STOCRIN 200 mg tablets

17. UNIQUE IDENTIFIED – 2D BARCODE

Outer carton: 2D barcode carrying the unique identifier included.

18. UNIQUE IDENTIFIED – HUMAN READABLE DATA

Outer carton
PC: 
SN:
NN:

 



77

B. PACKAGE LEAFLET

 



78

Package leaflet: Information for the user

Stocrin 30 mg/ml oral solution 
efavirenz

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Stocrin is and what it is used for
2. What you need to know before you take Stocrin
3. How to take Stocrin
4. Possible side effects
5. How to store Stocrin
6. Contents of the pack and other information

1. What Stocrin is and what it is used for

Stocrin, which contains the active substance efavirenz, belongs to a class of antiretroviral medicines 
called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that 
fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood.
It is used by adults, adolescents and children 3 years of age and older.

Your doctor has prescribed Stocrin for you because you have HIV infection. Stocrin taken in 
combination with other antiretroviral medicines reduces the amount of the virus in the blood. This will 
strengthen your immune system and reduce the risk of developing illnesses linked to HIV infection.

2. What you need to know before you take Stocrin

Do not take Stocrin:
 if you are allergic to efavirenz or any of the other ingredients of this medicine (listed in 

section 6). Contact your doctor or pharmacist for advice.

 if you have severe liver disease.

 if you have a heart condition, such as changes in the rhythm or rate of the heart beat, a 
slow heart beat, or severe heart disease.

 if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due  
to a heart problem or was born with heart problems. 

 if your doctor has told you that you have high or low levels of electrolytes such as potassium or 
magnesium in your blood.

 if you are currently taking any of the following medicines (see also “Other medicines and 
Stocrin”): 

- astemizole or terfenadine (used to treat allergy symptoms)  

 



79

- bepridil (used to treat heart disease)
- cisapride (used to treat heartburn)
- ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and 

methylergonovine) (used to treat migraine and cluster headaches)
- midazolam or triazolam (used to help you sleep)
- pimozide, imipramine, amitriptyline or clomipramine (used to treat certain 

mental conditions)
- St. John's wort (Hypericum perforatum) (a herbal remedy used for depression 

and anxiety)
- flecainide, metoprolol (used to treat irregular heart beat)
- certain antibiotics (macrolides, fluoroquinolones, imidazole) 
- triazole antifungal agents
- certain antimalarial treatments
- methadone (used to treat opiate addiction)
- elbasvir/grazoprevir

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines 
with Stocrin could create the potential for serious and/or life-threatening side-effects or stop Stocrin 
from working properly.

Warnings and precautions

Talk to you doctor before taking Stocrin

 Stocrin must be taken with other medicines that act against the HIV virus. If Stocrin is 
started because your current treatment has not prevented the virus from multiplying, another 
medicine you have not taken before must be started at the same time.

 You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy. It is important to take precautions to avoid infecting other people through 
sexual contact or blood transfer. Discuss with your doctor the precautions needed to avoid 
infecting other people. This medicine is not a cure for HIV infection and you may continue to 
develop infections or other illnesses associated with HIV disease.

 You must remain under the care of your doctor while taking Stocrin.

 Tell your doctor:

- if you have a history of mental illness, including depression, or of substance or 
alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal 
thoughts or have strange thoughts (see section 4, Possible side effects).

- if you have a history of convulsions (fits or seizures) or if you are being treated 
with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. 
If you are taking any of these medicines, your doctor may need to check the level 
of anticonvulsant medicine in your blood to ensure that it is not affected while 
taking Stocrin. Your doctor may give you a different anticonvulsant.

- if you have a history of liver disease, including active chronic hepatitis.  
Patients with chronic hepatitis B or C and treated with combination antiretroviral 
agents have a higher risk for severe and potentially life-threatening liver problems. 
Your doctor may conduct blood tests in order to check how well your liver is 
working or may switch you to another medicine. If you have severe liver disease, 
do not take Stocrin (see Section 2, Do not take Stocrin).

- if you have a heart disorder, such as abnormal electrical signal called 
prolongation of the QT interval.

 



80

 Once you start taking Stocrin, look out for:

- signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or 
abnormal dreaming. These side effects may start in the first 1 or 2 days of 
treatment and usually go away after the first 2 to 4 weeks.

- any signs of skin rash. If you see any signs of a severe rash with blistering or 
fever, stop taking Stocrin and tell your doctor at once. If you had a rash while 
taking another NNRTI, you may be at a higher risk of getting a rash with Stocrin.

- any signs of inflammation or infection. In some patients with advanced HIV 
infection (AIDS) and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is 
started. It is believed that these symptoms are due to an improvement in the body’s 
immune response, enabling the body to fight infections that may have been present 
with no obvious symptoms. If you notice any symptoms of infection, please tell 
your doctor immediately.
In addition to the opportunistic infections, autoimmune disorders (a condition that 
occurs when the immune system attacks healthy body tissue) may also occur after 
you start taking medicines for the treatment of your HIV infection. Autoimmune 
disorders may occur many months after the start of treatment. If you notice any 
symptoms of infection or other symptoms such as muscle weakness, weakness 
beginning in the hands and feet and moving up towards the trunk of the body, 
palpitations, tremor or hyperactivity, please inform your doctor immediately to 
seek necessary treatment.

- bone problems. Some patients taking combination antiretroviral therapy may 
develop a bone disease called osteonecrosis (death of bone tissue caused by loss of 
blood supply to the bone). The length of combination antiretroviral therapy, 
corticosteroid use, alcohol consumption, severe immunosuppression, higher body 
mass index, among others, may be some of the many risk factors for developing 
this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially 
of the hip, knee and shoulder) and difficulty in movement. If you notice any of 
these symptoms please inform your doctor.

Children and adolescents
Stocrin is not recommended for children under the age of 3 years or weighing less than 13 kg because 
it has not been adequately studied in these patients.

Other medicines and Stocrin
You must not take Stocrin with certain medicines. These are listed under Do not take Stocrin, at the 
start of Section 2. They include some common medicines and a herbal remedy (St. John’s wort) which 
can cause serious interactions.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

 



81

Stocrin may interact with other medicines, including herbal preparations such as Ginkgo biloba
extracts. As a result, the amounts of Stocrin or other medicines in your blood may be affected. This 
may stop the medicines from working properly, or may make any side effects worse. In some cases, 
your doctor may need to adjust your dose or check your blood levels. It is important to tell your 
doctor or pharmacist if you are taking any of the following:

 Other medicines used for HIV infection:
- protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir boosted 

atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you 
an alternative medicine or changing the dose of the protease inhibitors.

- maraviroc
- the combination tablet containing efavirenz, emtricitabine and tenofovir should not be 

taken with Stocrin unless recommended by your doctor since it contains efavirenz, the 
active ingredient of Stocrin.

 Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, 
simeprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir and 
sofosbuvir/velpatasvir/voxilaprevir.

 Medicines used to treat bacterial infections, including tuberculosis and AIDS-related
mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may 
consider changing your dose or giving you an alternative antibiotic. In addition, your doctor 
may prescribe a higher dose of Stocrin.

 Medicines used to treat fungal infections (antifungals):
- voriconazole. Stocrin may reduce the amount of voriconazole in your blood and 

voriconazole may increase the amount of Stocrin in your blood. If you take these two 
medicines together, the dose of voriconazole must be increased and the dose of efavirenz 
must be reduced. You must check with your doctor first.

- itraconazole. Stocrin may reduce the amount of itraconazole in your blood.
- posaconazole. Stocrin may reduce the amount of posaconazole in your blood.

 Medicines used to treat malaria:
- artemether/lumefantrine: Stocrin may reduce the amount of artemether/lumefantrine in 

your blood.
- atovaquone/proguanil: Stocrin may reduce the amount of atovaquone/proguanil in your 

blood.

 Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, 
phenobarbital. Stocrin can reduce or increase the amount of anticonvulsant in your blood. 
Carbamazepine may make Stocrin less likely to work. Your doctor may need to consider giving 
you a different anticonvulsant.

 Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. 
Stocrin can reduce the amount of statins in your blood. Your doctor will check your cholesterol 
levels and will consider changing the dose of your statin, if needed.

 Methadone (a medicine used to treat opiate addiction): your doctor may recommend an 
alternative treatment.

 Sertraline (a medicine used to treat depression): your doctor may need to change your dose of 
sertraline.

 Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may 
need to change your dose of bupropion.  

 



82

 Diltiazem or similar medicines (called calcium channel blockers which are medicines 
typically used for high blood pressure or heart problems): when you start taking Stocrin, 
your doctor may need to adjust your dose of the calcium channel blocker.

 Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to 
prevent organ transplant rejection): when you start or stop taking Stocrin, your doctor will 
closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

 Hormonal contraceptive, such as birth control pills, an injected contraceptive (for 
example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must 
also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). 
Stocrin may make hormonal contraceptives less likely to work. Pregnancies have occurred in 
women taking Stocrin while using a contraceptive implant, although it has not been established 
that the Stocrin therapy caused the contraceptive to fail.

 Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may 
need to adjust your dose of warfarin or acenocoumarol.

 Ginkgo biloba extracts (herbal preparation)

 Medicines that impact heart rhythm:
- Medicines used to treat heart rhythm problems such as flecainide or metoprolol.
- Medicines used to treat depression such as imipramine, amitriptyline or clomipramine.
- Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole.

Pregnancy and breast-feeding
Women should not get pregnant during treatment with Stocrin and for 12 weeks thereafter. Your 
doctor may require you to take a pregnancy test to ensure you are not pregnant before starting 
treatment with Stocrin.

If you could get pregnant while receiving Stocrin, you need to use a reliable form of barrier 
contraception (for example, a condom) with other methods of contraception including oral (pill) or 
other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood 
for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as 
above, for 12 weeks after you stop taking Stocrin.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are 
pregnant, you should take Stocrin only if you and your doctor decide it is clearly needed. Ask your 
doctor or pharmacist for advice before taking any medicine.

Serious birth defects have been seen in unborn animals and in the babies of women treated with 
efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during 
pregnancy. If you have taken Stocrin or the combination tablet containing efavirenz, emtricitabine, and 
tenofovir during your pregnancy, your doctor may request regular blood tests and other diagnostic 
tests to monitor the development of your child.

You should not breast feed your baby if you are taking Stocrin.

Driving and using machines
Stocrin contains efavirenz and may cause dizziness, impaired concentration, and drowsiness. 
If you are affected, do not drive and do not use any tools or machines.

3. How to take Stocrin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing.

 



83

 The dose for adults is 24 ml once daily.
 The dose for Stocrin may need to be increased or decreased if you are also taking certain

medicines (see Other medicines and Stocrin).
 Stocrin oral solution may be taken with or without food.

The dose of Stocrin oral solution in mg is not the same as for Stocrin film-coated tablets.

 Stocrin must be taken every day.
 Stocrin should never be used alone to treat HIV. Stocrin must always be taken in combination 

with other anti-HIV medicines.

The dose of Stocrin oral solution must be measured using the oral syringe 
supplied in the carton.  

 On first use, the bottle adapter must be fitted into the neck of the 
bottle. To do this, remove the child-resistant cap and the foil seal. The 
bottle adapter, which is already fixed to the nozzle of the syringe, can 
then be fitted into the neck of the bottle and pressed firmly down.  

 Separate the syringe from the adapter. The adapter should now fit 
closely to the neck so that the cap can be replaced without removing 
it.

 With the bottle upright, fit the tip of the syringe into the bottle adapter.  

 Turn the bottle upside down with the syringe still in place. Hold the 
bottle and the syringe firmly in one hand and with the other hand pull 
back the plunger slightly beyond the mark for the dose required. If air 
bubbles appear in the syringe, keep the bottle upside down and slowly 
push in the plunger and pull it back again. Repeat until there are no 
bubbles in the syringe.

 To measure the dose accurately, keep the bottle upside down and push 
the plunger in slowly until the top of the black ring (the edge nearest 
the syringe tip) lines up with the dose. Turn the bottle the right way up 
and remove the syringe. Wipe the adapter and replace the cap tightly 
over it.

 



84

 Before giving the dose of the oral solution make sure that the patient 
is sitting or standing upright. Put the tip of the syringe just inside the 
mouth, pointing it towards the cheek. Press the plunger slowly to 
allow time for the medicine to be swallowed. Rapid squirting into the 
mouth may cause choking.

After use, soak the syringe in warm soapy water for at least a minute. Draw the warm soapy water into 
the syringe until full and then empty completely. Repeat at least three times. Remove the plunger rod 
from the barrel and thoroughly rinse both parts with warm running water. If parts of the syringe are 
not clean, repeat the cleaning instructions. Allow the parts to dry completely prior to reassembly. Do 
not put the syringe in a dishwasher.

Use in children and adolescents
 The dose for children weighing 40 kg or more is 24 ml once daily.
 The dose for children weighing less than 40 kg is calculated by body weight and is taken once 

daily as shown below:

Body Weight Stocrin oral solution (30 mg/ml)
kg Dose (ml)

3 - < 5 years 5 years or more

13 to < 15 12 9
15 to < 20 13 10
20 to < 25 15 12

25 to < 32.5 17 15
32.5 to < 40 - 17

 40 - 24

If you take more Stocrin than you should
If you take too much Stocrin contact your doctor or nearest emergency department for advice. Keep 
the medicine container with you so that you can easily describe what you have taken.

If you forget to take Stocrin
Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a 
double dose to make up for a forgotten dose. If you need help in planning the best times to take your 
medicine, ask your doctor or pharmacist.

If you stop taking Stocrin
When your Stocrin supply starts to run low, get more from your doctor or pharmacist. This is very 
important because the amount of virus may start to increase if the medicine is stopped for even a short 
time. The virus may then become harder to treat.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. When 
treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Stocrin or by other medicines that you are taking at the same time, or by the HIV disease 
itself.

 



85

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

The most notable unwanted effects reported with Stocrin in combination with other anti-HIV 
medicines are skin rash and nervous system symptoms. 

You should consult your doctor if you have a rash, since some rashes may be serious; however, most 
cases of rash disappear without any change to your treatment with Stocrin. Rash was more common in 
children than in adults treated with Stocrin.

The nervous system symptoms tend to occur when treatment is first started, but generally decrease in 
the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours 
after taking a dose. If you are affected your doctor may suggest that you take Stocrin at bedtime. Some 
patients have more serious symptoms that may affect mood or the ability to think clearly. Some 
patients have actually committed suicide. These problems tend to occur more often in those who have 
a history of mental illness. Always notify your doctor immediately if you have these symptoms or any 
side effects while taking Stocrin.

Diarrhoea occurred in children who took Stocrin oral solution and nelfinavir in combination with other 
antiretroviral medicines.

Tell your doctor if you notice any of the following side effects:

Very common (affects more than 1 user in 10)
- skin rash

Common (affects 1 to 10 users in 100)
- abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, 

problems with coordination or balance
- stomach pain, diarrhoea, feeling sick (nausea), vomiting
- itching
- tiredness
- feeling anxious, feeling depressed
Tests may show:
- increased liver enzymes in the blood
- increased triglycerides (fatty acids) in the blood

Uncommon (affects 1 to 10 users in 1,000)
- nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts
- blurred vision
- a feeling of spinning or tilting (vertigo)
- pain in the abdomen (stomach) caused by inflammation of the pancreas
- allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, 

Stevens-Johnson syndrome)
- yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the 

liver
- breast enlargement in males
- angry behaviour, mood being affected, seeing or hearing things that are not really there 

(hallucinations), mania (mental condition characterised by episodes of overactivity, elation or 
irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered 
motionless and speechless for a period)

- whistling, ringing or other persistent noise in the ears
- tremor (shaking)
- flushing
Tests may show:
- increased cholesterol in the blood

 



86

Rare (affects 1 to 10 users in 10,000)
- itchy rash caused by a reaction to sunlight
- liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. 

Most cases occurred in patients who already had liver disease, but there have been a few reports 
in patients without any existing liver disease.

- unexplained feelings of distress not associated with hallucinations, but it may be difficult to 
think clearly or sensibly

- suicide

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Stocrin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month.

The bottle of Stocrin oral solution should be used within one month after first opening.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Stocrin contains

 Each ml of Stocrin oral solution contains 30 mg of the active substance efavirenz.
 The other ingredients are: medium chain triglycerides, benzoic acid (E210) and strawberry/mint 

flavour.

What Stocrin looks like and contents of the pack

Stocrin 30 mg/ml oral solution is supplied in bottles of 180 ml. An oral syringe with a push-in 
bottle-neck adapter is included in the carton.

Marketing Authorisation Holder Manufacturer 

Merck Sharp & Dohme B.V. Merck Sharp & Dohme B.V.
Waarderweg 39 Waarderweg 39
2031 BN Haarlem Postbus 581
The Netherlands 2003 PC Haarlem

The Netherlands

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


87

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak @merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44 82 40 00
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
Bristol-Myers Squibb GmbH & CO. KGaA
Tel: +49 89 121 42-0

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε
Τηλ: + 30-210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Bristol-Myers Squibb, S.A.
Tel: +34 91 456 53 00

Polska
MSD Polska Sp. z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

France
Bristol-Myers Squibb Sarl.
Tél: +33 (0) 810 410 500

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

 

mailto:inform_pt@merck.com


88

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +353 (1 800) 749 749

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak @merck.com

Ιtalia
Bristol-Myers Squibb S.r.l.
Tel: +39 06 50 39 61

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0)77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +44 (0800) 731 1736

This leaflet was last revised in 

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 



89

Package leaflet: Information for the user

Stocrin 600 mg film-coated tablets
efavirenz

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Stocrin is and what it is used for
2. What you need to know before you take Stocrin
3. How to take Stocrin
4. Possible side effects
5. How to store Stocrin
6. Contents of the pack and other information

1. What Stocrin is and what it is used for

Stocrin, which contains the active substance efavirenz, belongs to a class of antiretroviral medicines 
called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that 
fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood.
It is used by adults, adolescents and children 3 years of age and older.

Your doctor has prescribed Stocrin for you because you have HIV infection. Stocrin taken in 
combination with other antiretroviral medicines reduces the amount of the virus in the blood. This will 
strengthen your immune system and reduce the risk of developing illnesses linked to HIV infection.

2. What you need to know before you take Stocrin

Do not take Stocrin:
 if you are allergic to efavirenz or any of the other ingredients of this medicine (listed in 

section 6). Contact your doctor or pharmacist for advice.

 if you have severe liver disease.

 if you have a heart condition, such as changes in the rhythm or rate of the heart beat, a 
slow heart beat, or severe heart disease.

 if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due 
to a heart problem or was born with heart problems. 

 if your doctor has told you that you have high or low levels of electrolytes such as potassium or 

magnesium in your blood.

 



90

 if you are currently taking any of the following medicines (see also “Other medicines and 
Stocrin”): 

- astemizole or terfenadine (used to treat allergy symptoms)  
- bepridil (used to treat heart disease)
- cisapride (used to treat heartburn)
- ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and 

methylergonovine) (used to treat migraine and cluster headaches)
- midazolam or triazolam (used to help you sleep)
- pimozide, imipramine, amitriptyline or clomipramine (used to treat certain 

mental conditions)
- St. John's wort (Hypericum perforatum) (a herbal remedy used for depression 

and anxiety)
- flecainide, metoprolol (used to treat irregular heart beat)
- certain antibiotics (macrolides, fluoroquinolones, imidazole) 
- triazole antifungal agents
- certain antimalarial treatments
- methadone (used to treat opiate addiction)
- elbasvir/grazoprevir

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines 
with Stocrin could create the potential for serious and/or life-threatening side-effects or stop Stocrin 
from working properly.

Warnings and precautions

Talk to you doctor before taking Stocrin

 Stocrin must be taken with other medicines that act against the HIV virus. If Stocrin is 
started because your current treatment has not prevented the virus from multiplying, another 
medicine you have not taken before must be started at the same time.

 You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy. It is important to take precautions to avoid infecting other people through 
sexual contact or blood transfer. Discuss with your doctor the precautions needed to avoid 
infecting other people. This medicine is not a cure for HIV infection and you may continue to 
develop infections or other illnesses associated with HIV disease.

 You must remain under the care of your doctor while taking Stocrin.

 Tell your doctor:

- if you have a history of mental illness, including depression, or of substance or 
alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal 
thoughts or have strange thoughts (see section 4, Possible side effects).

- if you have a history of convulsions (fits or seizures) or if you are being treated 
with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. 
If you are taking any of these medicines, your doctor may need to check the level 
of anticonvulsant medicine in your blood to ensure that it is not affected while 
taking Stocrin. Your doctor may give you a different anticonvulsant.

- if you have a history of liver disease, including active chronic hepatitis.  
Patients with chronic hepatitis B or C and treated with combination antiretroviral 
agents have a higher risk for severe and potentially life-threatening liver problems. 
Your doctor may conduct blood tests in order to check how well your liver is 

 



91

working or may switch you to another medicine. If you have severe liver disease, 
do not take Stocrin (see Section 2, Do not take Stocrin).

- if you have a heart disorder, such as abnormal electrical signal called 
prolongation of the QT interval.

 Once you start taking Stocrin, look out for:

- signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or 
abnormal dreaming. These side effects may start in the first 1 or 2 days of 
treatment and usually go away after the first 2 to 4 weeks.

- any signs of skin rash. If you see any signs of a severe rash with blistering or 
fever, stop taking Stocrin and tell your doctor at once. If you had a rash while 
taking another NNRTI, you may be at a higher risk of getting a rash with Stocrin.

- any signs of inflammation or infection. In some patients with advanced HIV 
infection (AIDS) and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is 
started. It is believed that these symptoms are due to an improvement in the body’s 
immune response, enabling the body to fight infections that may have been present 
with no obvious symptoms. If you notice any symptoms of infection, please tell 
your doctor immediately.
In addition to the opportunistic infections, autoimmune disorders (a condition that 
occurs when the immune system attacks healthy body tissue) may also occur after 
you start taking medicines for the treatment of your HIV infection. Autoimmune 
disorders may occur many months after the start of treatment. If you notice any 
symptoms of infection or other symptoms such as muscle weakness, weakness 
beginning in the hands and feet and moving up towards the trunk of the body, 
palpitations, tremor or hyperactivity, please inform your doctor immediately to 
seek necessary treatment.

- bone problems. Some patients taking combination antiretroviral therapy may 
develop a bone disease called osteonecrosis (death of bone tissue caused by loss of 
blood supply to the bone). The length of combination antiretroviral therapy, 
corticosteroid use, alcohol consumption, severe immunosuppression, higher body 
mass index, among others, may be some of the many risk factors for developing 
this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially 
of the hip, knee and shoulder) and difficulty in movement. If you notice any of 
these symptoms please inform your doctor.

Children and adolescents
Stocrin is not recommended for children under the age of 3 years or weighing less than 13 kg because 
it has not been adequately studied in these patients.

Other medicines and Stocrin
You must not take Stocrin with certain medicines. These are listed under Do not take Stocrin, at the 
start of Section 2. They include some common medicines and a herbal remedy (St. John’s wort) which 
can cause serious interactions.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

Stocrin may interact with other medicines, including herbal preparations such as Ginkgo biloba
extracts. As a result, the amounts of Stocrin or other medicines in your blood may be affected. This 
may stop the medicines from working properly, or may make any side effects worse. In some cases, 

 



92

your doctor may need to adjust your dose or check your blood levels. It is important to tell your 
doctor or pharmacist if you are taking any of the following:

 Other medicines used for HIV infection:
- protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir boosted 

atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you 
an alternative medicine or changing the dose of the protease inhibitors.

- maraviroc
- the combination tablet containing efavirenz, emtricitabine and tenofovir should not be 

taken with Stocrin unless recommended by your doctor since it contains efavirenz, the 
active ingredient of Stocrin.

 Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, 
simeprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir and 
sofosbuvir/velpatasvir/voxilaprevir.

 Medicines used to treat bacterial infections, including tuberculosis and AIDS-related
mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may 
consider changing your dose or giving you an alternative antibiotic. In addition, your doctor 
may prescribe a higher dose of Stocrin.

 Medicines used to treat fungal infections (antifungals):
- voriconazole. Stocrin may reduce the amount of voriconazole in your blood and 

voriconazole may increase the amount of Stocrin in your blood. If you take these two 
medicines together, the dose of voriconazole must be increased and the dose of efavirenz 
must be reduced. You must check with your doctor first.

- itraconazole. Stocrin may reduce the amount of itraconazole in your blood.
- posaconazole. Stocrin may reduce the amount of posaconazole in your blood.

 Medicines used to treat malaria:
- artemether/lumefantrine: Stocrin may reduce the amount of artemether/lumefantrine in 

your blood.
- atovaquone/proguanil: Stocrin may reduce the amount of atovaquone/proguanil in your 

blood.

 Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, 
phenobarbital. Stocrin can reduce or increase the amount of anticonvulsant in your blood. 
Carbamazepine may make Stocrin less likely to work. Your doctor may need to consider giving 
you a different anticonvulsant.

 Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. 
Stocrin can reduce the amount of statins in your blood. Your doctor will check your cholesterol 
levels and will consider changing the dose of your statin, if needed.

 Methadone (a medicine used to treat opiate addiction): your doctor may recommend an 
alternative treatment.

 Sertraline (a medicine used to treat depression): your doctor may need to change your dose of 
sertraline.

 Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may 
need to change your dose of bupropion.

 Diltiazem or similar medicines (called calcium channel blockers which are medicines 
typically used for high blood pressure or heart problems): when you start taking Stocrin, 
your doctor may need to adjust your dose of the calcium channel blocker.

 



93

 Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to 
prevent organ transplant rejection): when you start or stop taking Stocrin, your doctor will 
closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

 Hormonal contraceptive, such as birth control pills, an injected contraceptive (for 
example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must 
also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). 
Stocrin may make hormonal contraceptives less likely to work. Pregnancies have occurred in 
women taking Stocrin while using a contraceptive implant, although it has not been established 
that the Stocrin therapy caused the contraceptive to fail.

 Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may 
need to adjust your dose of warfarin or acenocoumarol.

 Ginkgo biloba extracts (herbal preparation)

 Medicines that impact heart rhythm:
- Medicines used to treat heart rhythm problems such as flecainide or metoprolol.
- Medicines used to treat depression such as imipramine, amitriptyline or clomipramine.
- Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole.

Stocrin with food and drink
Taking Stocrin on an empty stomach may reduce the undesirable effects. Grapefruit juice should be 
avoided when taking Stocrin.

Pregnancy and breast-feeding
Women should not get pregnant during treatment with Stocrin and for 12 weeks thereafter. Your 
doctor may require you to take a pregnancy test to ensure you are not pregnant before starting 
treatment with Stocrin.

If you could get pregnant while receiving Stocrin, you need to use a reliable form of barrier 
contraception (for example, a condom) with other methods of contraception including oral (pill) or 
other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood 
for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as 
above, for 12 weeks after you stop taking Stocrin.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are 
pregnant, you should take Stocrin only if you and your doctor decide it is clearly needed. Ask your 
doctor or pharmacist for advice before taking any medicine.

Serious birth defects have been seen in unborn animals and in the babies of women treated with 
efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during 
pregnancy. If you have taken Stocrin or the combination tablet containing efavirenz, emtricitabine, and 
tenofovir during your pregnancy, your doctor may request regular blood tests and other diagnostic 
tests to monitor the development of your child.

You should not breast feed your baby if you are taking Stocrin.

Driving and using machines
Stocrin contains efavirenz and may cause dizziness, impaired concentration, and drowsiness. 
If you are affected, do not drive and do not use any tools or machines.

Stocrin contains lactose in each 600-mg daily dose.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. Individuals with these conditions may take Stocrin oral solution, 
which is free from lactose. 

 



94

3. How to take Stocrin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing.

 The dose for adults is 600 mg once daily.
 The dose for Stocrin may need to be increased or decreased if you are also taking certain 

medicines (see Other medicines and Stocrin).
 Stocrin is for oral use. Stocrin is recommended to be taken on an empty stomach preferably at 

bedtime. This may make some side effects (for example, dizziness, drowsiness) less 
troublesome. An empty stomach is commonly defined as 1 hour before or 2 hours after a meal.

 It is recommended that the tablet be swallowed whole with water.
 Stocrin must be taken every day.
 Stocrin should never be used alone to treat HIV. Stocrin must always be taken in combination 

with other anti-HIV medicines.

Use in children and adolescents
 The dose for children weighing 40 kg or more is 600 mg once daily.
 The dose for children weighing less than 40 kg is calculated by body weight and is taken once 

daily as shown below:

Body Weight Stocrin
kg Dose (mg)*

13 to < 15 200
15 to < 20 250
20 to < 25 300

25 to < 32.5 350
32.5 to < 40 400

 Stocrin 50 mg, 200 mg and 600 mg film-coated tablets are available.

If you take more Stocrin than you should
If you take too much Stocrin contact your doctor or nearest emergency department for advice. Keep 
the medicine container with you so that you can easily describe what you have taken.

If you forget to take Stocrin
Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a 
double dose to make up for a forgotten dose. If you need help in planning the best times to take your 
medicine, ask your doctor or pharmacist.

If you stop taking Stocrin
When your Stocrin supply starts to run low, get more from your doctor or pharmacist. This is very 
important because the amount of virus may start to increase if the medicine is stopped for even a short 
time. The virus may then become harder to treat.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. When 
treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Stocrin or by other medicines that you are taking at the same time, or by the HIV disease 
itself.

 



95

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

The most notable unwanted effects reported with Stocrin in combination with other anti-HIV 
medicines are skin rash and nervous system symptoms. 

You should consult your doctor if you have a rash, since some rashes may be serious; however, most 
cases of rash disappear without any change to your treatment with Stocrin. Rash was more common in 
children than in adults treated with Stocrin.

The nervous system symptoms tend to occur when treatment is first started, but generally decrease in 
the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours 
after taking a dose. If you are affected your doctor may suggest that you take Stocrin at bedtime and 
on an empty stomach. Some patients have more serious symptoms that may affect mood or the ability 
to think clearly. Some patients have actually committed suicide. These problems tend to occur more 
often in those who have a history of mental illness. Always notify your doctor immediately if you have 
these symptoms or any side effects while taking Stocrin.

Tell your doctor if you notice any of the following side effects:

Very common (affects more than 1 user in 10)
- skin rash

Common (affects 1 to 10 users in 100)
- abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, 

problems with coordination or balance
- stomach pain, diarrhoea, feeling sick (nausea), vomiting
- itching
- tiredness
- feeling anxious, feeling depressed
Tests may show:
- increased liver enzymes in the blood
- increased triglycerides (fatty acids) in the blood

Uncommon (affects 1 to 10 users in 1,000)
- nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts
- blurred vision
- a feeling of spinning or tilting (vertigo)
- pain in the abdomen (stomach) caused by inflammation of the pancreas
- allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, 

Stevens-Johnson syndrome)
- yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the 

liver
- breast enlargement in males
- angry behaviour, mood being affected, seeing or hearing things that are not really there 

(hallucinations), mania (mental condition characterised by episodes of overactivity, elation or 
irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered 
motionless and speechless for a period)

- whistling, ringing or other persistent noise in the ears
- tremor (shaking)
- flushing
Tests may show:
- increased cholesterol in the blood

Rare (affects 1 to 10 users in 10,000)
- itchy rash caused by a reaction to sunlight

 



96

- liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. 
Most cases occurred in patients who already had liver disease, but there have been a few reports 
in patients without any existing liver disease.

- unexplained feelings of distress not associated with hallucinations, but it may be difficult to 
think clearly or sensibly

- suicide

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Stocrin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Stocrin contains

 Each Stocrin film-coated tablet contains 600 mg of the active substance efavirenz.
 The other ingredients of the tablet core are: croscarmellose sodium, microcrystalline cellulose, 

sodium laurilsulfate, hydroxypropylcellulose, lactose monohydrate and magnesium stearate.
 The film coating contains: hypromellose (E464), titanium dioxide (E171), macrogol 400, yellow 

iron oxide (E172), and carnauba wax. 

What Stocrin looks like and contents of the pack

Stocrin 600 mg film-coated tablets are supplied in bottles of 30 tablets.

Marketing Authorisation Holder Manufacturer 

Merck Sharp & Dohme B.V. Merck Sharp & Dohme B.V.
Waarderweg 39 Waarderweg 39
2031 BN Haarlem Postbus 581
The Netherlands 2003 PC Haarlem

The Netherlands

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

 

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97

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak @merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44 82 40 00
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
Bristol-Myers Squibb GmbH & CO. KGaA
Tel: +49 89 121 42-0

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε
Τηλ: + 30-210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Bristol-Myers Squibb, S.A.
Tel: +34 91 456 53 00

Polska
MSD Polska Sp. z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

France
Bristol-Myers Squibb Sarl.
Tél: +33 (0) 810 410 500

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +353 (1 800) 749 749

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak @merck.com

 

mailto:inform_pt@merck.com


98

Ιtalia
Bristol-Myers Squibb S.r.l.
Tel: +39 06 50 39 61

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0)77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +44 (0800) 731 1736

This leaflet was last revised in 

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 



99

Package leaflet: Information for the user

Stocrin 50 mg film-coated tablets 
efavirenz

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Stocrin is and what it is used for
2. What you need to know before you take Stocrin
3. How to take Stocrin
4. Possible side effects
5. How to store Stocrin
6. Contents of the pack and other information

1. What Stocrin is and what it is used for

Stocrin, which contains the active substance efavirenz, belongs to a class of antiretroviral medicines 
called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that 
fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood.
It is used by adults, adolescents and children 3 years of age and older.

Your doctor has prescribed Stocrin for you because you have HIV infection. Stocrin taken in 
combination with other antiretroviral medicines reduces the amount of the virus in the blood. This will 
strengthen your immune system and reduce the risk of developing illnesses linked to HIV infection

2. What you need to know before you take Stocrin

Do not take Stocrin:
 if you are allergic to efavirenz or any of the other ingredients of this medicine (listed in 

section 6). Contact your doctor or pharmacist for advice.

 if you have severe liver disease.

 if you have a heart condition, such as changes in the rhythm or rate of the heart beat, a 
slow heart beat, or severe heart disease.

 if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due 
to a heart problem or was born with heart problems. 

 if your doctor has told you that you have high or low levels of electrolytes such as potassium or 

magnesium in your blood.

 if you are currently taking any of the following medicines (see also “Other medicines and 
Stocrin”): 

- astemizole or terfenadine (used to treat allergy symptoms)  

 



100

- bepridil (used to treat heart disease)
- cisapride (used to treat heartburn)
- ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and 

methylergonovine) (used to treat migraine and cluster headaches)
- midazolam or triazolam (used to help you sleep)
- pimozide, imipramine, amitriptyline or clomipramine (used to treat certain 

mental conditions)
- St. John's wort (Hypericum perforatum) (a herbal remedy used for depression 

and anxiety)
- flecainide, metoprolol (used to treat irregular heart beat)
- certain antibiotics (macrolides, fluoroquinolones, imidazole) 
- triazole antifungal agents
- certain antimalarial treatments
- methadone (used to treat opiate addiction)
- elbasvir/grazoprevir

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines 
with Stocrin could create the potential for serious and/or life-threatening side-effects or stop Stocrin
from working properly.

Warnings and precautions

Talk to you doctor before taking Stocrin

 Stocrin must be taken with other medicines that act against the HIV virus. If Stocrin is 
started because your current treatment has not prevented the virus from multiplying, another 
medicine you have not taken before must be started at the same time.

 You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy. It is important to take precautions to avoid infecting other people through 
sexual contact or blood transfer. Discuss with your doctor the precautions needed to avoid 
infecting other people. This medicine is not a cure for HIV infection and you may continue to 
develop infections or other illnesses associated with HIV disease.

 You must remain under the care of your doctor while taking Stocrin.

 Tell your doctor:

- if you have a history of mental illness, including depression, or of substance or 
alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal 
thoughts or have strange thoughts (see section 4, Possible side effects).

- if you have a history of convulsions (fits or seizures) or if you are being treated 
with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. 
If you are taking any of these medicines, your doctor may need to check the level 
of anticonvulsant medicine in your blood to ensure that it is not affected while 
taking Stocrin. Your doctor may give you a different anticonvulsant.

- if you have a history of liver disease, including active chronic hepatitis.
Patients with chronic hepatitis B or C and treated with combination antiretroviral 
agents have a higher risk for severe and potentially life-threatening liver problems. 
Your doctor may conduct blood tests in order to check how well your liver is 
working or may switch you to another medicine. If you have severe liver disease, 
do not take Stocrin (see Section 2, Do not take Stocrin).

- if you have a heart disorder, such as abnormal electrical signal called 
prolongation of the QT interval.

 



101

 Once you start taking Stocrin, look out for:

- signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or 
abnormal dreaming. These side effects may start in the first 1 or 2 days of 
treatment and usually go away after the first 2 to 4 weeks.

- any signs of skin rash. If you see any signs of a severe rash with blistering or 
fever, stop taking Stocrin and tell your doctor at once. If you had a rash while 
taking another NNRTI, you may be at a higher risk of getting a rash with Stocrin.

- any signs of inflammation or infection. In some patients with advanced HIV 
infection (AIDS) and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is 
started. It is believed that these symptoms are due to an improvement in the body’s 
immune response, enabling the body to fight infections that may have been present 
with no obvious symptoms. If you notice any symptoms of infection, please tell 
your doctor immediately.
In addition to the opportunistic infections, autoimmune disorders (a condition that 
occurs when the immune system attacks healthy body tissue) may also occur after 
you start taking medicines for the treatment of your HIV infection. Autoimmune 
disorders may occur many months after the start of treatment. If you notice any 
symptoms of infection or other symptoms such as muscle weakness, weakness 
beginning in the hands and feet and moving up towards the trunk of the body, 
palpitations, tremor or hyperactivity, please inform your doctor immediately to 
seek necessary treatment.

- bone problems. Some patients taking combination antiretroviral therapy may 
develop a bone disease called osteonecrosis (death of bone tissue caused by loss of 
blood supply to the bone). The length of combination antiretroviral therapy, 
corticosteroid use, alcohol consumption, severe immunosuppression, higher body 
mass index, among others, may be some of the many risk factors for developing 
this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially 
of the hip, knee and shoulder) and difficulty in movement. If you notice any of
these symptoms please inform your doctor.

Children and adolescents
Stocrin is not recommended for children under the age of 3 years or weighing less than 13 kg because 
it has not been adequately studied in these patients

Other medicines and Stocrin
You must not take Stocrin with certain medicines. These are listed under Do not take Stocrin, at the 
start of Section 2. They include some common medicines and a herbal remedy (St. John’s wort) which 
can cause serious interactions.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

 



102

Stocrin may interact with other medicines, including herbal preparations such as Ginkgo biloba
extracts. As a result, the amounts of Stocrin or other medicines in your blood may be affected. This 
may stop the medicines from working properly, or may make any side effects worse. In some cases, 
your doctor may need to adjust your dose or check your blood levels. It is important to tell your 
doctor or pharmacist if you are taking any of the following:

 Other medicines used for HIV infection:
- protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir boosted 

atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you 
an alternative medicine or changing the dose of the protease inhibitors.

- maraviroc
- the combination tablet containing efavirenz, emtricitabine and tenofovir should not be 

taken with Stocrin unless recommended by your doctor since it contains efavirenz, the 
active ingredient of Stocrin.

 Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, 
simeprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir and 
sofosbuvir/velpatasvir/voxilaprevir.

 Medicines used to treat bacterial infections, including tuberculosis and AIDS-related
mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may 
consider changing your dose or giving you an alternative antibiotic. In addition, your doctor 
may prescribe a higher dose of Stocrin.

 Medicines used to treat fungal infections (antifungals):
- voriconazole. Stocrin may reduce the amount of voriconazole in your blood and 

voriconazole may increase the amount of Stocrin in your blood. If you take these two 
medicines together, the dose of voriconazole must be increased and the dose of efavirenz 
must be reduced. You must check with your doctor first.

- itraconazole. Stocrin may reduce the amount of itraconazole in your blood.
- posaconazole. Stocrin may reduce the amount of posaconazole in your blood.

 Medicines used to treat malaria:
- artemether/lumefantrine: Stocrin may reduce the amount of artemether/lumefantrine in 

your blood.
- atovaquone/proguanil: Stocrin may reduce the amount of atovaquone/proguanil in your 

blood.

 Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, 
phenobarbital. Stocrin can reduce or increase the amount of anticonvulsant in your blood. 
Carbamazepine may make Stocrin less likely to work. Your doctor may need to consider giving 
you a different anticonvulsant.

 Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. 
Stocrin can reduce the amount of statins in your blood. Your doctor will check your cholesterol 
levels and will consider changing the dose of your statin, if needed.

 Methadone (a medicine used to treat opiate addiction): your doctor may recommend an 
alternative treatment.

 Sertraline (a medicine used to treat depression): your doctor may need to change your dose of 
sertraline.

 Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may 
need to change your dose of bupropion.

 



103

 Diltiazem or similar medicines (called calcium channel blockers which are medicines 
typically used for high blood pressure or heart problems): when you start taking Stocrin, 
your doctor may need to adjust your dose of the calcium channel blocker.

 Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to 
prevent organ transplant rejection): when you start or stop taking Stocrin, your doctor will 
closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

 Hormonal contraceptive, such as birth control pills, an injected contraceptive (for 
example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must 
also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). 
Stocrin may make hormonal contraceptives less likely to work. Pregnancies have occurred in 
women taking Stocrin while using a contraceptive implant, although it has not been established 
that the Stocrin therapy caused the contraceptive to fail.

 Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may 
need to adjust your dose of warfarin or acenocoumarol.

 Ginkgo biloba extracts (herbal preparation)

 Medicines that impact heart rhythm:
- Medicines used to treat heart rhythm problems such as flecainide or metoprolol.
- Medicines used to treat depression such as imipramine, amitriptyline or clomipramine.
- Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole.

Stocrin with food and drink
Taking Stocrin on an empty stomach may reduce the undesirable effects. Grapefruit juice should be 
avoided when taking Stocrin

Pregnancy and breast-feeding
Women should not get pregnant during treatment with Stocrin and for 12 weeks thereafter. Your 
doctor may require you to take a pregnancy test to ensure you are not pregnant before starting 
treatment with Stocrin.

If you could get pregnant while receiving Stocrin, you need to use a reliable form of barrier 
contraception (for example, a condom) with other methods of contraception including oral (pill) or 
other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood 
for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as 
above, for 12 weeks after you stop taking Stocrin.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are 
pregnant, you should take Stocrin only if you and your doctor decide it is clearly needed. Ask your 
doctor or pharmacist for advice before taking any medicine.

Serious birth defects have been seen in unborn animals and in the babies of women treated with 
efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during 
pregnancy. If you have taken Stocrin or the combination tablet containing efavirenz, emtricitabine, and 
tenofovir during your pregnancy, your doctor may request regular blood tests and other diagnostic 
tests to monitor the development of your child.

You should not breast feed your baby if you are taking Stocrin.

Driving and using machines
Stocrin contains efavirenz and may cause dizziness, impaired concentration, and drowsiness. 
If you are affected, do not drive and do not use any tools or machines.

 



104

Stocrin contains lactose in each 600-mg daily dose.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. Individuals with these conditions may take Stocrin oral solution, 
which is free from lactose. 

3. How to take Stocrin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing.

 The dose for adults is 600 mg once daily.
 The dose for Stocrin may need to be increased or decreased if you are also taking certain 

medicines (see Other medicines and Stocrin).
 Stocrin is for oral use. Stocrin is recommended to be taken on an empty stomach preferably at 

bedtime. This may make some side effects (for example, dizziness, drowsiness) less 
troublesome. An empty stomach is commonly defined as 1 hour before or 2 hours after a meal.

 It is recommended that the tablet be swallowed whole with water.
 Stocrin must be taken every day.
 Stocrin should never be used alone to treat HIV. Stocrin must always be taken in combination 

with other anti-HIV medicines.

Use in children and adolescents
 The dose for children weighing 40 kg or more is 600 mg once daily.
 The dose for children weighing less than 40 kg is calculated by body weight and is taken once 

daily as shown below:

Body Weight Stocrin
kg Dose (mg)*

13 to < 15 200
15 to < 20 250
20 to < 25 300

25 to < 32.5 350
32.5 to < 40 400

 Stocrin 50 mg, 200 mg and 600 mg film-coated tablets are available.

If you take more Stocrin than you should
If you take too much Stocrin contact your doctor or nearest emergency department for advice. Keep 
the medicine container with you so that you can easily describe what you have taken.

If you forget to take Stocrin
Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a 
double dose to make up for a forgotten dose. If you need help in planning the best times to take your 
medicine, ask your doctor or pharmacist.

If you stop taking Stocrin
When your Stocrin supply starts to run low, get more from your doctor or pharmacist. This is very 
important because the amount of virus may start to increase if the medicine is stopped for even a short 
time. The virus may then become harder to treat.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

 



105

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. When 
treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Stocrin or by other medicines that you are taking at the same time, or by the HIV disease 
itself.

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

The most notable unwanted effects reported with Stocrin in combination with other anti-HIV 
medicines are skin rash and nervous system symptoms. 

You should consult your doctor if you have a rash, since some rashes may be serious; however, most 
cases of rash disappear without any change to your treatment with Stocrin. Rash was more common in 
children than in adults treated with Stocrin.

The nervous system symptoms tend to occur when treatment is first started, but generally decrease in 
the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours 
after taking a dose. If you are affected your doctor may suggest that you take Stocrin at bedtime and 
on an empty stomach. Some patients have more serious symptoms that may affect mood or the ability 
to think clearly. Some patients have actually committed suicide. These problems tend to occur more 
often in those who have a history of mental illness. Always notify your doctor immediately if you have 
these symptoms or any side effects while taking Stocrin.

Tell your doctor if you notice any of the following side effects:

Very common (affects more than 1 user in 10)
- skin rash

Common (affects 1 to 10 users in 100)
- abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, 

problems with coordination or balance
- stomach pain, diarrhoea, feeling sick (nausea), vomiting
- itching
- tiredness
- feeling anxious, feeling depressed
Tests may show:
- increased liver enzymes in the blood
- increased triglycerides (fatty acids) in the blood

Uncommon (affects 1 to 10 users in 1,000)
- nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts
- blurred vision
- a feeling of spinning or tilting (vertigo)
- pain in the abdomen (stomach) caused by inflammation of the pancreas
- allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, 

Stevens-Johnson syndrome)
- yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the 

liver
- breast enlargement in males
- angry behaviour, mood being affected, seeing or hearing things that are not really there 

(hallucinations), mania (mental condition characterised by episodes of overactivity, elation or 
irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered 
motionless and speechless for a period)

- whistling, ringing or other persistent noise in the ears

 



106

- tremor (shaking)
- flushing
Tests may show:
- increased cholesterol in the blood

Rare (affects 1 to 10 users in 10,000)
- itchy rash caused by a reaction to sunlight
- liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. 

Most cases occurred in patients who already had liver disease, but there have been a few reports 
in patients without any existing liver disease.

- unexplained feelings of distress not associated with hallucinations, but it may be difficult to 
think clearly or sensibly

- suicide

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine.

5. How to store Stocrin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Stocrin contains

 Each Stocrin film-coated tablet contains 50 mg of the active substance efavirenz.
 The other ingredients of the tablet core are: croscarmellose sodium, microcrystalline cellulose, 

sodium laurilsulfate, hydroxypropylcellulose, lactose monohydrate and magnesium stearate.
 The film coating contains: hypromellose (E464), titanium dioxide (E171), macrogol 400, yellow 

iron oxide (E172), and carnauba wax.

What Stocrin looks like and contents of the pack

Stocrin 50 mg film-coated tablets are supplied in bottles of 30 tablets.

Marketing Authorisation Holder Manufacturer 

Merck Sharp & Dohme B.V. Merck Sharp & Dohme B.V.
Waarderweg 39 Waarderweg 39
2031 BN Haarlem Postbus 581
The Netherlands 2003 PC Haarlem

The Netherlands

 

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107

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak @merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44 82 40 00
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
Bristol-Myers Squibb GmbH & CO. KGaA
Tel: +49 89 121 42-0

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε
Τηλ: + 30-210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Bristol-Myers Squibb, S.A.
Tel: +34 91 456 53 00

Polska
MSD Polska Sp. z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

France
Bristol-Myers Squibb Sarl.
Tél: +33 (0) 810 410 500

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

 

mailto:inform_pt@merck.com


108

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +353 (1 800) 749 749

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak @merck.com

Ιtalia
Bristol-Myers Squibb S.r.l.
Tel: +39 06 50 39 61

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0)77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +44 (0800) 731 1736

This leaflet was last revised in 

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 



109

Package leaflet: Information for the user

Stocrin 200 mg film-coated tablets
efavirenz

Read all of this leaflet carefully before you start taking this medicine because it contains 
important information for you. 
 Keep this leaflet. You may need to read it again.
 If you have any further questions, ask your doctor, pharmacist or nurse.
 This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

even if their signs of illness are the same as yours.
 If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible 

side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Stocrin is and what it is used for
2. What you need to know before you take Stocrin
3. How to take Stocrin
4. Possible side effects
5. How to store Stocrin
6. Contents of the pack and other information

1. What Stocrin is and what it is used for

Stocrin, which contains the active substance efavirenz, belongs to a class of antiretroviral medicines 
called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that 
fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood.
It is used by adults, adolescents and children 3 years of age and older.

Your doctor has prescribed Stocrin for you because you have HIV infection. Stocrin taken in 
combination with other antiretroviral medicines reduces the amount of the virus in the blood. This will 
strengthen your immune system and reduce the risk of developing illnesses linked to HIV infection.

2. What you need to know before you take Stocrin

Do not take Stocrin:
 if you are allergic to efavirenz or any of the other ingredients of this medicine (listed in 

section 6). Contact your doctor or pharmacist for advice.

 if you have severe liver disease.

 if you have a heart condition, such as changes in the rhythm or rate of the heart beat, a 
slow heart beat, or severe heart disease.

 if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due 
to a heart problem or was born with heart problems. 

 if your doctor has told you that you have high or low levels of electrolytes such as potassium or 

magnesium in your blood.

 if you are currently taking any of the following medicines (see also “Other medicines and 
Stocrin”): 

- astemizole or terfenadine (used to treat allergy symptoms)  

 



110

- bepridil (used to treat heart disease)
- cisapride (used to treat heartburn)
- ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and 

methylergonovine) (used to treat migraine and cluster headaches)
- midazolam or triazolam (used to help you sleep)
- pimozide, imipramine, amitriptyline or clomipramine (used to treat certain 

mental conditions)
- St. John's wort (Hypericum perforatum) (a herbal remedy used for depression 

and anxiety)
- flecainide, metoprolol (used to treat irregular heart beat)
- certain antibiotics (macrolides, fluoroquinolones, imidazole) 
- triazole antifungal agents
- certain antimalarial treatments
- methadone (used to treat opiate addiction)
- elbasvir/grazoprevir

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines 
with Stocrin could create the potential for serious and/or life-threatening side-effects or stop Stocrin 
from working properly.

Warnings and precautions

Talk to you doctor before taking Stocrin

 Stocrin must be taken with other medicines that act against the HIV virus. If Stocrin is 
started because your current treatment has not prevented the virus from multiplying, another 
medicine you have not taken before must be started at the same time.

 You can still pass on HIV when taking this medicine, although the risk is lowered by effective 
antiretroviral therapy. It is important to take precautions to avoid infecting other people through 
sexual contact or blood transfer. Discuss with your doctor the precautions needed to avoid 
infecting other people. This medicine is not a cure for HIV infection and you may continue to 
develop infections or other illnesses associated with HIV disease.

 You must remain under the care of your doctor while taking Stocrin.

 Tell your doctor:

- if you have a history of mental illness, including depression, or of substance or 
alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal 
thoughts or have strange thoughts (see section 4, Possible side effects).

- if you have a history of convulsions (fits or seizures) or if you are being treated 
with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. 
If you are taking any of these medicines, your doctor may need to check the level 
of anticonvulsant medicine in your blood to ensure that it is not affected while 
taking Stocrin. Your doctor may give you a different anticonvulsant.

- if you have a history of liver disease, including active chronic hepatitis.  
Patients with chronic hepatitis B or C and treated with combination antiretroviral 
agents have a higher risk for severe and potentially life-threatening liver problems. 
Your doctor may conduct blood tests in order to check how well your liver is 
working or may switch you to another medicine. If you have severe liver disease, 
do not take Stocrin (see Section 2, Do not take Stocrin).

- if you have a heart disorder, such as abnormal electrical signal called 
prolongation of the QT interval.

 



111

 Once you start taking Stocrin, look out for:

- signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or 
abnormal dreaming. These side effects may start in the first 1 or 2 days of 
treatment and usually go away after the first 2 to 4 weeks.

- any signs of skin rash. If you see any signs of a severe rash with blistering or 
fever, stop taking Stocrin and tell your doctor at once. If you had a rash while 
taking another NNRTI, you may be at a higher risk of getting a rash with Stocrin.

- any signs of inflammation or infection. In some patients with advanced HIV 
infection (AIDS) and a history of opportunistic infection, signs and symptoms of 
inflammation from previous infections may occur soon after anti-HIV treatment is 
started. It is believed that these symptoms are due to an improvement in the body’s 
immune response, enabling the body to fight infections that may have been present 
with no obvious symptoms. If you notice any symptoms of infection, please tell 
your doctor immediately.
In addition to the opportunistic infections, autoimmune disorders (a condition that 
occurs when the immune system attacks healthy body tissue) may also occur after 
you start taking medicines for the treatment of your HIV infection. Autoimmune 
disorders may occur many months after the start of treatment. If you notice any 
symptoms of infection or other symptoms such as muscle weakness, weakness 
beginning in the hands and feet and moving up towards the trunk of the body, 
palpitations, tremor or hyperactivity, please inform your doctor immediately to 
seek necessary treatment.

- bone problems. Some patients taking combination antiretroviral therapy may 
develop a bone disease called osteonecrosis (death of bone tissue caused by loss of 
blood supply to the bone). The length of combination antiretroviral therapy, 
corticosteroid use, alcohol consumption, severe immunosuppression, higher body 
mass index, among others, may be some of the many risk factors for developing 
this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially 
of the hip, knee and shoulder) and difficulty in movement. If you notice any of 
these symptoms please inform your doctor.

Children and adolescents
Stocrin is not recommended for children under the age of 3 years or weighing less than 13 kg because 
it has not been adequately studied in these patients

Other medicines and Stocrin
You must not take Stocrin with certain medicines. These are listed under Do not take Stocrin, at the 
start of Section 2. They include some common medicines and a herbal remedy (St. John’s wort) which 
can cause serious interactions.

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other 
medicines.

 



112

Stocrin may interact with other medicines, including herbal preparations such as Ginkgo biloba
extracts. As a result, the amounts of Stocrin or other medicines in your blood may be affected. This 
may stop the medicines from working properly, or may make any side effects worse. In some cases, 
your doctor may need to adjust your dose or check your blood levels. It is important to tell your 
doctor or pharmacist if you are taking any of the following:

 Other medicines used for HIV infection:
- protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir, ritonavir boosted 

atazanavir, saquinavir or fosamprenavir/saquinavir. Your doctor may consider giving you 
an alternative medicine or changing the dose of the protease inhibitors.

- maraviroc
- the combination tablet containing efavirenz, emtricitabine and tenofovir should not be 

taken with Stocrin unless recommended by your doctor since it contains efavirenz, the 
active ingredient of Stocrin.

 Medicines used to treat infection with the hepatitis C virus: boceprevir, telaprevir, 
simeprevir, sofosbuvir/velpatasvir, glecaprevir/pibrentasvir and 
sofosbuvir/velpatasvir/voxilaprevir.

 Medicines used to treat bacterial infections, including tuberculosis and AIDS-related
mycobacterium avium complex: clarithromycin, rifabutin, rifampicin. Your doctor may 
consider changing your dose or giving you an alternative antibiotic. In addition, your doctor 
may prescribe a higher dose of Stocrin.

 Medicines used to treat fungal infections (antifungals):
- voriconazole. Stocrin may reduce the amount of voriconazole in your blood and 

voriconazole may increase the amount of Stocrin in your blood. If you take these two 
medicines together, the dose of voriconazole must be increased and the dose of efavirenz 
must be reduced. You must check with your doctor first.

- itraconazole. Stocrin may reduce the amount of itraconazole in your blood.
- posaconazole. Stocrin may reduce the amount of posaconazole in your blood.

 Medicines used to treat malaria:
- artemether/lumefantrine: Stocrin may reduce the amount of artemether/lumefantrine in 

your blood.
- atovaquone/proguanil: Stocrin may reduce the amount of atovaquone/proguanil in your 

blood.

 Medicines used to treat convulsions/seizures (anticonvulsants): carbamazepine, phenytoin, 
phenobarbital. Stocrin can reduce or increase the amount of anticonvulsant in your blood. 
Carbamazepine may make Stocrin less likely to work. Your doctor may need to consider giving
you a different anticonvulsant.

 Medicines used to lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. 
Stocrin can reduce the amount of statins in your blood. Your doctor will check your cholesterol 
levels and will consider changing the dose of your statin, if needed.

 Methadone (a medicine used to treat opiate addiction): your doctor may recommend an 
alternative treatment.

 Sertraline (a medicine used to treat depression): your doctor may need to change your dose of 
sertraline.

 Bupropion (a medicine used to treat depression or to help you stop smoking): your doctor may 
need to change your dose of bupropion. 

 



113

 Diltiazem or similar medicines (called calcium channel blockers which are medicines 
typically used for high blood pressure or heart problems): when you start taking Stocrin, 
your doctor may need to adjust your dose of the calcium channel blocker.

 Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus (medicines used to 
prevent organ transplant rejection): when you start or stop taking Stocrin, your doctor will 
closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

 Hormonal contraceptive, such as birth control pills, an injected contraceptive (for 
example, Depo-Provera), or a contraceptive implant (for example, Implanon): you must 
also use a reliable barrier method of contraception (see Pregnancy, breast-feeding and fertility). 
Stocrin may make hormonal contraceptives less likely to work. Pregnancies have occurred in 
women taking Stocrin while using a contraceptive implant, although it has not been established 
that the Stocrin therapy caused the contraceptive to fail.

 Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): your doctor may 
need to adjust your dose of warfarin or acenocoumarol.

 Ginkgo biloba extracts (herbal preparation)

 Medicines that impact heart rhythm:
- Medicines used to treat heart rhythm problems such as flecainide or metoprolol.
- Medicines used to treat depression such as imipramine, amitriptyline or clomipramine.
- Antibiotics, including the following types: macrolides, fluoroquinolones or imidazole.

Stocrin with food and drink
Taking Stocrin on an empty stomach may reduce the undesirable effects. Grapefruit juice should be 
avoided when taking Stocrin.

Pregnancy and breast-feeding
Women should not get pregnant during treatment with Stocrin and for 12 weeks thereafter. Your 
doctor may require you to take a pregnancy test to ensure you are not pregnant before starting 
treatment with Stocrin.

If you could get pregnant while receiving Stocrin, you need to use a reliable form of barrier 
contraception (for example, a condom) with other methods of contraception including oral (pill) or 
other hormonal contraceptives (for example, implants, injection). Efavirenz may remain in your blood 
for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as 
above, for 12 weeks after you stop taking Stocrin.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are 
pregnant, you should take Stocrin only if you and your doctor decide it is clearly needed. Ask your 
doctor or pharmacist for advice before taking any medicine.

Serious birth defects have been seen in unborn animals and in the babies of women treated with 
efavirenz or a combination medicine containing efavirenz, emtricitabine and tenofovir during 
pregnancy. If you have taken Stocrin or the combination tablet containing efavirenz, emtricitabine, and 
tenofovir during your pregnancy, your doctor may request regular blood tests and other diagnostic 
tests to monitor the development of your child.

You should not breast feed your baby if you are taking Stocrin.

Driving and using machines
Stocrin contains efavirenz and may cause dizziness, impaired concentration, and drowsiness. 
If you are affected, do not drive and do not use any tools or machines.

 



114

Stocrin contains lactose in each 600-mg daily dose.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor 
before taking this medicinal product. Individuals with these conditions may take Stocrin oral solution, 
which is free from lactose. 

3. How to take Stocrin

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure. Your doctor will give you instructions for proper dosing.

 The dose for adults is 600 mg once daily.
 The dose for Stocrin may need to be increased or decreased if you are also taking certain 

medicines (see Other medicines and Stocrin).
 Stocrin is for oral use. Stocrin is recommended to be taken on an empty stomach preferably at 

bedtime. This may make some side effects (for example, dizziness, drowsiness) less 
troublesome. An empty stomach is commonly defined as 1 hour before or 2 hours after a meal.

 It is recommended that the tablet be swallowed whole with water. 
 Stocrin must be taken every day.
 Stocrin should never be used alone to treat HIV. Stocrin must always be taken in combination 

with other anti-HIV medicines.

Use in children and adolescents
 The dose for children weighing 40 kg or more is 600 mg once daily.
 The dose for children weighing less than 40 kg is calculated by body weight and is taken once 

daily as shown below:

Body Weight Stocrin
kg Dose (mg)*

13 to < 15 200
15 to < 20 250
20 to < 25 300

25 to < 32.5 350
32.5 to < 40 400

 Stocrin 50 mg, 200 mg and 600 mg film-coated tablets are available.

If you take more Stocrin than you should
If you take too much Stocrin contact your doctor or nearest emergency department for advice. Keep 
the medicine container with you so that you can easily describe what you have taken.

If you forget to take Stocrin
Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a 
double dose to make up for a forgotten dose. If you need help in planning the best times to take your 
medicine, ask your doctor or pharmacist.

If you stop taking Stocrin
When your Stocrin supply starts to run low, get more from your doctor or pharmacist. This is very 
important because the amount of virus may start to increase if the medicine is stopped for even a short 
time. The virus may then become harder to treat.

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

 



115

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them. When 
treating HIV infection, it is not always possible to tell whether some of the unwanted effects are 
caused by Stocrin or by other medicines that you are taking at the same time, or by the HIV disease 
itself.

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This 
is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV 
medicines themselves. Your doctor will test for these changes.

The most notable unwanted effects reported with Stocrin in combination with other anti-HIV 
medicines are skin rash and nervous system symptoms. 

You should consult your doctor if you have a rash, since some rashes may be serious; however, most 
cases of rash disappear without any change to your treatment with Stocrin. Rash was more common in 
children than in adults treated with Stocrin.

The nervous system symptoms tend to occur when treatment is first started, but generally decrease in 
the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours 
after taking a dose. If you are affected your doctor may suggest that you take Stocrin at bedtime and 
on an empty stomach. Some patients have more serious symptoms that may affect mood or the ability 
to think clearly. Some patients have actually committed suicide. These problems tend to occur more 
often in those who have a history of mental illness. Always notify your doctor immediately if you have 
these symptoms or any side effects while taking Stocrin.

Tell your doctor if you notice any of the following side effects:

Very common (affects more than 1 user in 10)
- skin rash

Common (affects 1 to 10 users in 100)
- abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, 

problems with coordination or balance
- stomach pain, diarrhoea, feeling sick (nausea), vomiting
- itching
- tiredness
- feeling anxious, feeling depressed
Tests may show:
- increased liver enzymes in the blood
- increased triglycerides (fatty acids) in the blood

Uncommon (affects 1 to 10 users in 1,000)
- nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts
- blurred vision
- a feeling of spinning or tilting (vertigo)
- pain in the abdomen (stomach) caused by inflammation of the pancreas
- allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, 

Stevens-Johnson syndrome)
- yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the 

liver
- breast enlargement in males
- angry behaviour, mood being affected, seeing or hearing things that are not really there 

(hallucinations), mania (mental condition characterised by episodes of overactivity, elation or 
irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered 
motionless and speechless for a period)

- whistling, ringing or other persistent noise in the ears

 



116

- tremor (shaking)
- flushing
Tests may show:
- increased cholesterol in the blood

Rare (affects 1 to 10 users in 10,000)
- itchy rash caused by a reaction to sunlight
- liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. 

Most cases occurred in patients who already had liver disease, but there have been a few reports 
in patients without any existing liver disease.

- unexplained feelings of distress not associated with hallucinations, but it may be difficult to 
think clearly or sensibly

- suicide

Reporting of side effects
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the
safety of this medicine.

5. How to store Stocrin

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the bottle and on the carton after 
EXP. The expiry date refers to the last day of that month.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Stocrin contains

 Each Stocrin film-coated tablet contains 200 mg of the active substance efavirenz.
 The other ingredients of the tablet core are: croscarmellose sodium, microcrystalline cellulose, 

sodium laurilsulfate, hydroxypropylcellulose, lactose monohydrate and magnesium stearate.  
 The film coating contains: hypromellose (E464), titanium dioxide (E171), macrogol 400, yellow 

iron oxide (E172), and carnauba wax.

What Stocrin looks like and contents of the pack

Stocrin 200 mg film-coated tablets are supplied in bottles of 90.

Marketing Authorisation Holder Manufacturer 

Merck Sharp & Dohme B.V. Merck Sharp & Dohme B.V.
Waarderweg 39 Waarderweg 39
2031 BN Haarlem Postbus 581
The Netherlands 2003 PC Haarlem

The Netherlands

 

http://www.ema.europa.eu/docs/en_GB/document_library/Template_or_form/2013/03/WC500139752.doc


117

For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder:

Belgique/België/Belgien
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Lietuva
UAB Merck Sharp & Dohme
Tel.: +370 5 278 02 47
msd_lietuva@merck.com

България
Мерк Шарп и Доум България ЕООД
Тел.: +359 2 819 3737
info-msdbg@merck.com

Luxembourg/Luxemburg
MSD Belgium BVBA/SPRL
Tél/Tel: +32(0)27766211
dpoc_belux@merck.com

Česká republika
Merck Sharp & Dohme s.r.o.
Tel.: +420 233 010 111
dpoc_czechslovak @merck.com

Magyarország
MSD Pharma Hungary Kft.
Tel.: +361 888 53 00
hungary_msd@merck.com

Danmark
MSD Danmark ApS
Tlf: +45 44 82 40 00
dkmail@merck.com

Malta
Merck Sharp & Dohme Cyprus Limited
Tel: 8007 4433 (+356 99917558)
malta_info@merck.com

Deutschland
Bristol-Myers Squibb GmbH & CO. KGaA
Tel: +49 89 121 42-0

Nederland
Merck Sharp & Dohme B.V.
Tel: 0800 9999000 (+31 23 5153153)
medicalinfo.nl@merck.com

Eesti
Merck Sharp & Dohme OÜ
Tel.: +372 6144 200
msdeesti@merck.com

Norge
MSD (Norge) AS
Tlf: +47 32 20 73 00
msdnorge@msd.no

Eλλάδα
MSD Α.Φ.Β.Ε.Ε
Τηλ: + 30-210 98 97 300
dpoc_greece@merck.com

Österreich
Merck Sharp & Dohme Ges.m.b.H.
Tel: +43 (0) 1 26 044
msd-medizin@merck.com

España
Bristol-Myers Squibb, S.A.
Tel: +34 91 456 53 00

Polska
MSD Polska Sp. z o.o.
Tel.: +48 22 549 51 00
msdpolska@merck.com

Hrvatska
Merck Sharp & Dohme d.o.o.
Tel: + 385 1 6611 333
croatia_info@merck.com

Portugal
Merck Sharp & Dohme, Lda
Tel: +351 21 4465700
inform_pt@merck.com

France
Bristol-Myers Squibb Sarl.
Tél: +33 (0) 810 410 500

România
Merck Sharp & Dohme Romania S.R.L.
Tel: + 4021 529 29 00
msdromania@merck.com

 

mailto:inform_pt@merck.com


118

Ireland
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +353 (1 800) 749 749

Slovenija
Merck Sharp & Dohme, inovativna zdravila 
d.o.o.
Tel: + 386 1 5204201
msd_slovenia@merck.com

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
Merck Sharp & Dohme, s. r. o.
Tel.: +421 2 58282010
dpoc_czechslovak @merck.com

Ιtalia
Bristol-Myers Squibb S.r.l.
Tel: +39 06 50 39 61

Suomi/Finland
MSD Finland Oy
Puh/Tel: +358 (0) 9 804650
info@msd.fi

Κύπρος
Merck Sharp & Dohme Cyprus Limited
Τηλ: 80000 673 (+357 22866700)
cyprus_info@merck.com

Sverige
Merck Sharp & Dohme (Sweden) AB
Tel: +46 (0)77 5700488
medicinskinfo@merck.com

Latvija
SIA Merck Sharp & Dohme Latvija
Tel: +371 67364 224
msd_lv@merck.com

United Kingdom
Bristol-Myers Squibb Pharmaceuticals Ltd.
Tel: +44 (0800) 731 1736

This leaflet was last revised in 

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE
	B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE
	C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING AUTHORISATION
	D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND EFFECTIVE USE OF THE MEDICINAL PRODUCT
	A. LABELLING
	B. PACKAGE LEAFLET
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{'Title': '3. how to take stocrin', 'Section_Content': 'always take this medicine exactly as your doctor or pharmacist has told you. check with your doctor or pharmacist if you are not sure. your doctor will give you instructions for proper dosing. the dose for adults is 24 ml once daily. the dose for stocrin may need to be increased or decreased if you are also taking certain medicines (see other medicines and stocrin). stocrin oral solution may be taken with or without food. the dose of stocrin oral solution in mg is not the same as for stocrin film-coated tablets. stocrin must be taken every day. stocrin should never be used alone to treat hiv. stocrin must always be taken in combination with other anti-hiv medicines. the dose of stocrin oral solution must be measured using the oral syringe supplied in the carton. on first use, the bottle adapter must be fitted into the neck of the bottle. to do this, remove the child-resistant cap and the foil seal. the bottle adapter, which is already fixed to the nozzle of the syringe, can then be fitted into the neck of the bottle and pressed firmly down. separate the syringe from the adapter. the adapter should now fit closely to the neck so that the cap can be replaced without removing it. with the bottle upright, fit the tip of the syringe into the bottle adapter. turn the bottle upside down with the syringe still in place. hold the bottle and the syringe firmly in one hand and with the other hand pull back the plunger slightly beyond the mark for the dose required. if air bubbles appear in the syringe, keep the bottle upside down and slowly push in the plunger and pull it back again. repeat until there are no bubbles in the syringe. to measure the dose accurately, keep the bottle upside down and push the plunger in slowly until the top of the black ring (the edge nearest the syringe tip) lines up with the dose. turn the bottle the right way up and remove the syringe. wipe the adapter and replace the cap tightly over it. before giving the dose of the oral solution make sure that the patient is sitting or standing upright. put the tip of the syringe just inside the mouth, pointing it towards the cheek. press the plunger slowly to allow time for the medicine to be swallowed. rapid squirting into the mouth may cause choking. after use, soak the syringe in warm soapy water for at least a minute. draw the warm soapy water into the syringe until full and then empty completely. repeat at least three times. remove the plunger rod from the barrel and thoroughly rinse both parts with warm running water. if parts of the syringe are not clean, repeat the cleaning instructions. allow the parts to dry completely prior to reassembly. do not put the syringe in a dishwasher. use in children and adolescents the dose for children weighing 40 kg or more is 24 ml once daily. the dose for children weighing less than 40 kg is calculated by body weight and is taken once daily as shown below: body weight stocrin oral solution (30 mg/ml) kg dose (ml) 3 - < 5 years 5 years or more 13 to < 15 12 9 15 to < 20 13 10 20 to < 25 15 12 25 to < 32.5 17 15 32.5 to < 40 - 17 40 - 24 if you take more stocrin than you should if you take too much stocrin contact your doctor or nearest emergency department for advice. keep the medicine container with you so that you can easily describe what you have taken. if you forget to take stocrin try not to miss a dose. if you do miss a dose, take the next dose as soon as possible, but do not take a double dose to make up for a forgotten dose. if you need help in planning the best times to take your medicine, ask your doctor or pharmacist. if you stop taking stocrin when your stocrin supply starts to run low, get more from your doctor or pharmacist. this is very important because the amount of virus may start to increase if the medicine is stopped for even a short time. the virus may then become harder to treat. if you have any further questions on the use of this medicine, 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{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. when treating hiv infection, it is not always possible to tell whether some of the unwanted effects are caused by stocrin or by other medicines that you are taking at the same time, or by the hiv disease itself. during hiv therapy there may be an increase in weight and in levels of blood lipids and glucose. this is partly linked to restored health and life style, and in the case of blood lipids sometimes to the hiv medicines themselves. your doctor will test for these changes. the most notable unwanted effects reported with stocrin in combination with other anti-hiv medicines are skin rash and nervous system symptoms. you should consult your doctor if you have a rash, since some rashes may be serious; however, most cases of rash disappear without any change to your treatment with stocrin. rash was more common in children than in adults treated with stocrin. the nervous system symptoms tend to occur when treatment is first started, but generally decrease in the first few weeks. in one study, nervous system symptoms often occurred during the first 1-3 hours after taking a dose. if you are affected your doctor may suggest that you take stocrin at bedtime. some patients have more serious symptoms that may affect mood or the ability to think clearly. some patients have actually committed suicide. these problems tend to occur more often in those who have a history of mental illness. always notify your doctor immediately if you have these symptoms or any side effects while taking stocrin. diarrhoea occurred in children who took stocrin oral solution and nelfinavir in combination with other antiretroviral medicines. tell your doctor if you notice any of the following side effects: very common (affects more than 1 user in 10) - skin rash common (affects 1 to 10 users in 100) - abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, problems with coordination or balance - stomach pain, diarrhoea, feeling sick (nausea), vomiting - itching - tiredness - feeling anxious, feeling depressed tests may show: - increased liver enzymes in the blood - increased triglycerides (fatty acids) in the blood uncommon (affects 1 to 10 users in 1,000) - nervousness, forgetfulness, confusion, fitting (seizures), abnormal thoughts - blurred vision - a feeling of spinning or tilting (vertigo) - pain in the abdomen (stomach) caused by inflammation of the pancreas - allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, stevens-johnson syndrome) - yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the liver - breast enlargement in males - angry behaviour, mood being affected, seeing or hearing things that are not really there (hallucinations), mania (mental condition characterised by episodes of overactivity, elation or irritability), paranoia, suicidal thoughts, catatonia (condition in which the patient is rendered motionless and speechless for a period) - whistling, ringing or other persistent noise in the ears - tremor (shaking) - flushing tests may show: - increased cholesterol in the blood 86 rare (affects 1 to 10 users in 10,000) - itchy rash caused by a reaction to sunlight - liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. most cases occurred in patients who already had liver disease, but there have been a few reports in patients without any existing liver disease. - unexplained feelings of distress not associated with hallucinations, but it may be difficult to think clearly or sensibly - suicide reporting of side effects if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national 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'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7459012269973755}]}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 4037, 'EndOffset': 4050}]}
{'Title': '5. how to store stocrin', 'Section_Content': 'keep this medicine out of the sight and reach of children. do not use this medicine after the expiry date which is stated on the bottle and on the carton after exp. the expiry date refers to the last day of that month. the bottle of stocrin oral solution should be used within one month after first opening. do not throw away any medicines via wastewater or household waste. ask your pharmacist how to throw away medicines you no longer use. these measures will help protect the environment.', 'Entity_Recognition': [{'Text': 'stocrin', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': 'stocrin oral solution', 'Type': 'TREATMENT', 'BeginOffset': 233, 'EndOffset': 254}, {'Id': 3, 'BeginOffset': 270, 'EndOffset': 286, 'Score': 0.9896768927574158, 'Text': 'within one month', 'Category': 'TIME_EXPRESSION', 'Type': 'TIME_TO_MEDICATION_NAME', 'Traits': [], 'Attributes': [{'Type': 'BRAND_NAME', 'Score': 0.6230162382125854, 'RelationshipScore': 0.6413793563842773, 'RelationshipType': 'OVERLAP', 'Id': 0, 'BeginOffset': 233, 'EndOffset': 240, 'Text': 'stocrin', 'Category': 'MEDICATION', 'Traits': []}]}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what stocrin contains each ml of stocrin oral solution contains 30 mg of the active substance efavirenz. the other ingredients are: medium chain triglycerides, benzoic acid (e210) and strawberry/mint flavour. what stocrin looks like and contents of the pack stocrin 30 mg/ml oral solution is supplied in bottles of 180 ml. an oral syringe with a push-in bottle-neck adapter is included in the carton.', 'Entity_Recognition': [{'Text': 'stocrin', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 5, 'EndOffset': 12, 'Score': 0.27115076780319214, 'Text': 'stocrin', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'stocrin oral solution', 'Type': 'TREATMENT', 'BeginOffset': 33, 'EndOffset': 54}, {'Text': '30', 'Type': 'NUMBER', 'BeginOffset': 64, 'EndOffset': 66}, {'Text': 'the active substance efavirenz', 'Type': 'TREATMENT', 'BeginOffset': 73, 'EndOffset': 103}, {'Text': 'medium chain triglycerides', 'Type': 'TEST', 'BeginOffset': 132, 'EndOffset': 158}, {'Id': 6, 'BeginOffset': 160, 'EndOffset': 172, 'Score': 0.7596604228019714, 'Text': 'benzoic acid', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'strawberry/mint flavour', 'Type': 'TREATMENT', 'BeginOffset': 184, 'EndOffset': 207}, {'Text': 'the pack stocrin', 'Type': 'TREATMENT', 'BeginOffset': 249, 'EndOffset': 265}, {'Text': '30', 'Type': 'NUMBER', 'BeginOffset': 266, 'EndOffset': 268}, {'Text': '180', 'Type': 'NUMBER', 'BeginOffset': 315, 'EndOffset': 318}, {'Text': 'an oral syringe', 'Type': 'TREATMENT', 'BeginOffset': 323, 'EndOffset': 338}, {'Text': 'a push-in bottle-neck adapter', 'Type': 'TREATMENT', 'BeginOffset': 344, 'EndOffset': 373}]}