Buvidal
1 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
  



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1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 8 mg prolonged-release solution for injection  
Buvidal 16 mg prolonged-release solution for injection  
Buvidal 24 mg prolonged-release solution for injection  
Buvidal 32 mg prolonged-release solution for injection  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
8 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 8 mg buprenorphine  
 
16 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 16 mg buprenorphine  
 
24 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 24 mg buprenorphine  
 
32 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 32 mg buprenorphine  
 
Excipient(s) with known effect 
 
The 8 mg, 16 mg, 24 mg and 32 mg strengths contain small amounts of ethanol (alcohol), less than 
100 mg per dose. 
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Prolonged-release solution for injection. 
Yellowish to yellow clear liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of opioid dependence within a framework of medical, social and psychological treatment. 
Treatment is intended for use in adults and adolescents aged 16 years or over. 
 
4.2 Posology and method of administration 
 
Administration of Buvidal is restricted to healthcare professionals. Appropriate precautions, such as to 
conduct patient follow-up visits with clinical monitoring according to the patient's needs, should be 
taken when prescribing and dispensing buprenorphine. Take-home use or self-administration of the 
product by patients is not allowed. 
 



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Precautions to be taken before initiation of treatment  
 
To avoid precipitating symptoms of withdrawal, treatment with Buvidal should be started when 
objective and clear signs of mild to moderate withdrawal are evident (see section 4.4). Consideration 
should be given to the types of opioid used (that is long- or short-acting opioid), time since last opioid 
use and the degree of opioid dependence. 
 
• For patients using heroin or short-acting opioids, the initial dose of Buvidal must not be 

administered until at least 6 hours after the patient last used opioids. 
• For patients receiving methadone, the methadone dose should be reduced to a maximum of 

30 mg/day before starting treatment with Buvidal which should not be administered until at 
least 24 hours after the patient last received a methadone dose. Buvidal may trigger withdrawal 
symptoms in methadone-dependent patients. 

 
Posology 
 
Initiation of treatment in patients not already receiving buprenorphine 
Patients not previously exposed to buprenorphine should receive a sublingual buprenorphine 4 mg 
dose and be observed for an hour before the first administration of weekly Buvidal to confirm 
tolerability to buprenorphine. 
 
The recommended starting dose of Buvidal is 16 mg, with one or two additional 8 mg doses at least 
1 day apart, to a target dose of 24 mg or 32 mg during the first treatment week. The recommended 
dose for the second treatment week is the total dose administered during the week of initiation.  
 
Treatment with monthly Buvidal can be started after treatment initiation with weekly Buvidal, in 
accordance with the dose conversion in Table 2 and once patients have been stabilised on weekly 
treatment (four weeks or more, where practical).  
 
Switching from sublingual buprenorphine products to Buvidal  
Patients treated with sublingual buprenorphine may be switched directly to weekly or monthly 
Buvidal, starting on the day after the last daily buprenorphine sublingual treatment dose in accordance 
with the dosing recommendations in Table 1. Closer monitoring of patients is recommended during 
the dosing period after the switch. 
 

Table 1. Conventional sublingual buprenorphine daily treatment doses and 
recommended corresponding doses of weekly and monthly Buvidal 

Dose of daily sublingual 
buprenorphine 

Dose of weekly Buvidal Dose of monthly Buvidal 

2-6 mg 8 mg   
8-10 mg  16 mg  64 mg  
12-16 mg  24 mg  96 mg  
18-24 mg  32 mg  128 mg  

 
The dose of buprenorphine in mg can differ between sublingual products, which needs to be taken into 
consideration on a product-by-product basis. The pharmacokinetic properties of Buvidal are described 
in section 5.2. 
 
Maintenance treatment and dose adjustments 
Buvidal can be administered weekly or monthly. Doses may be increased or decreased and patients 
can be switched between weekly and monthly products according to individual patient’s needs and 
treating physician’s clinical judgement as per recommendations in Table 2. Following switching, 
patients may need closer monitoring. Assessment of long-term treatment is based on 48-week data. 



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Table 2.  Recommended dose conversion when switching from weekly to monthly dosing 

or from monthly to weekly dosing 
Weekly dose of Buvidal Monthly dose of Buvidal 
16 mg 64 mg 
24 mg 96 mg 
32 mg 128 mg 

 
Supplemental dosing 
A maximum of one supplemental Buvidal 8 mg dose may be administered at an unscheduled visit 
between regular weekly and monthly doses, based on individual patient’s temporary needs. 
The maximum dose per week for patients who are on weekly Buvidal treatment is 32 mg with an 
additional 8 mg dose. The maximum dose per month for patients who are on monthly Buvidal 
treatment is 128 mg with an additional 8 mg dose.  
 
Missed doses 
To avoid missed doses, the weekly dose may be administered up to 2 days before or after the weekly 
time point, and the monthly dose may be administered up to 1 week before or after the monthly time 
point. 
 
If a dose is missed, the next dose should be administered as soon as practically possible.  
 
Termination of treatment 
If Buvidal treatment is discontinued, its prolonged-release characteristics and any withdrawal 
symptoms experienced by the patient must be considered, see section 4.4. If the patient is switched to 
treatment with sublingual buprenorphine, this should be done one week after the last weekly dose or 
one month after the last monthly dose of Buvidal according to the recommendations in Table 1. 
 
Special populations 
 
Elderly 
The efficacy and safety of buprenorphine in elderly patients > 65 years have not been established. No 
recommendation on posology can be made. 
 
In general, recommended dosing for elderly patients with normal renal function is the same as for 
younger adult patients with normal renal function. However, because elderly patients may have 
diminished renal/hepatic function, dose adjustment may be necessary (see Hepatic impairment and 
Renal impairment below). 
 
Hepatic impairment 
Buprenorphine should be used with caution in patients with moderate hepatic impairment (see 
section 5.2). In patients with severe hepatic impairment, the use of buprenorphine is contraindicated 
(see section 4.3). 
 
Renal impairment 
Modification of the buprenorphine dose is not required for patients with renal impairment. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance < 30 ml/min) 
(see sections 4.4 and 5.2). 
 
Paediatric population  
The safety and efficacy buprenorphine in children and adolescents below 16 years of age have not 
been established (see section 4.4). No data are available. 
 
Method of administration 
 
Buvidal is intended for subcutaneous administration only. It should be injected slowly and completely 
into the subcutaneous tissue of different areas (buttock, thigh, abdomen, or upper arm), provided there 



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is enough subcutaneous tissue. Each area can have multiple injection sites. Injection sites should be 
rotated for both weekly and monthly injections. A minimum of 8 weeks should be left before re-
injecting a previously used injection site with the weekly dose. There is no clinical data supporting 
reinjection of the monthly dose into the same site. This is unlikely to be a safety concern. The decision 
to reinject at the same site should also be guided by the attending physicians´ clinical judgement. 
Administered dose should be as a single injection and not divided. The dose must not be administered 
intravascularly (intravenously), intramuscularly or intradermally (into the skin) (see section 4.4). See 
section 6.6 for administration instructions. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
Severe respiratory insufficiency 
Severe hepatic impairment 
Acute alcoholism or delirium tremens 
 
4.4 Special warnings and precautions for use 
 
Administration 
 
Care must be taken to avoid inadvertent injection of Buvidal. The dose must not be administered 
intravascularly (intravenously), intramuscularly or intradermally.  
 
Intravascular such as intravenous injection would present a risk of serious harm as Buvidal forms a 
solid mass upon contact with body fluids, which potentially could cause blood vessel injury, 
occlusion, or thromboembolic events. 
 
To minimise the risk of misuse, abuse and diversion, appropriate precautions should be taken when 
prescribing and dispensing buprenorphine. Healthcare professionals should administer Buvidal 
directly to the patient. Take-home use or self-administration of the product by patients is not allowed. 
Any attempts to remove the depot should be monitored throughout treatment. 
 
Prolonged-release properties 
 
The prolonged-release properties of the product should be considered during treatment including 
initiation and termination. In particular, patients with concomitant medicinal products and/or co-
morbidities, should be monitored for signs and symptoms of toxicity, overdose or withdrawal caused 
by increased or decreased levels of buprenorphine. 
For pharmacokinetic properties, see section 5.2 and for treatment termination, see section 4.2. 
 
Respiratory depression 
 
A number of cases of death due to respiratory depression have been reported for patients being treated 
with buprenorphine, particularly when used in combination with benzodiazepines (see section 4.5) or 
when buprenorphine was not used according to prescribing information. Deaths have also been 
reported in association with concomitant administration of buprenorphine and other depressants such 
as alcohol, gabapentinoids (such as pregabalin and gabapentin) (see section 4.5) or other opioids.  
Buprenorphine should be used with care in patients with respiratory insufficiency (e.g. chronic 
obstructive pulmonary disease, asthma, cor pulmonale, decreased respiratory reserve, hypoxia, 
hypercapnia, pre-existing respiratory depression or kyphoscoliosis). 
 
Buprenorphine may cause severe, possibly fatal, respiratory depression in children and non-opioid 
dependent persons who accidentally or deliberately use it.  
 



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CNS depression 
 
Buprenorphine may cause drowsiness particularly when taken together with alcohol or central nervous 
system depressants such as benzodiazepines, tranquilisers, sedatives, gabapentinoids or hypnotics (see 
sections 4.5 and 4.7). 
 
Dependence 
 
Buprenorphine is a partial agonist at the mu-opiate receptor and chronic administration can produce 
opioid dependence.  
 
Hepatitis and hepatic events 
 
Baseline liver function tests and documentation of viral hepatitis status are recommended prior to 
starting therapy. Patients who are positive for viral hepatitis, on certain concomitant medicinal 
products (see section 4.5) and/or who have existing liver dysfunction are at greater risk of liver injury. 
Regular monitoring of the liver function is recommended. 
Cases of acute hepatic injury have been reported in opioid-dependent patients both in clinical studies 
and in post-marketing adverse reaction reports with medicinal products containing buprenorphine. The 
spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to 
case reports of cytolytic hepatitis, hepatic failure, hepatic necrosis, hepatorenal syndrome, hepatic 
encephalopathy and death. In many cases, the presence of pre-existing liver enzyme abnormalities, 
genetic disease, infection with hepatitis B or hepatitis C virus, alcohol abuse, anorexia, concomitant 
use of other potentially hepatotoxic medicinal products and ongoing injecting drug use may have a 
causative or contributory role. These underlying factors must be taken into consideration before 
prescribing buprenorphine and during treatment. When a hepatic event is suspected, further biological 
and aetiological evaluation is required. Depending on the findings, Buvidal may be discontinued. 
Monitoring beyond the weekly and monthly treatment period may be needed. If treatment is 
continued, hepatic function should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome 
 
When initiating treatment with buprenorphine, it is important to be aware of the partial agonist profile 
of buprenorphine. Buprenorphine products have caused precipitated withdrawal symptoms in opioid-
dependent patients when administered before the agonist effects resulting from recent opioid use or 
misuse have subsided. To avoid precipitated withdrawal, induction must be undertaken when objective 
signs and symptoms of mild to moderate withdrawal are evident (see section 4.2).  
Discontinuation of treatment may result in a withdrawal syndrome that may be delayed in onset. 
 
Hepatic impairment 
 
Buprenorphine is extensively metabolised in the liver. Patients with moderate hepatic impairment 
should be monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose 
caused by increased levels of buprenorphine. Buprenorphine should be used with caution in patients 
with moderate hepatic impairment (see sections 4.2 and 5.2). Hepatic function should be monitored 
regularly whilst on treatment. The use of buprenorphine is contraindicated in patients with severe 
hepatic impairment (see section 4.3). 
 
Renal impairment 
 
Metabolites of buprenorphine accumulate in patients with renal failure. Caution is recommended when 
dosing patients with severe renal impairment (creatinine clearance < 30 ml/min), see sections 4.2 and 
5.2. 
 



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QT prolongation 
 
Caution should be exercised when co-administering Buvidal with other medicinal products that 
prolong the QT interval and in patients with a history of long QT syndrome or other risk factors for 
QT prolongation. 
 
Acute pain management 
 
For management of acute pain during continued use of Buvidal, a combination of use of opioids with 
high mu-opioid receptor affinity (e.g. fentanyl), non-opioid analgesics and regional anaesthesia might 
be necessary. Titration of oral or intravenous short-acting opioid pain medicinal products (immediate-
release morphine, oxycodone or fentanyl) to the desired analgesic effect in patients treated with 
Buvidal might require higher doses. Patients should be monitored during treatment. 
 
Use in children and adolescents 
 
The safety and efficacy of buprenorphine in children below the age of 16 years have not been 
established (see section 4.2). Due to limited data in adolescents (aged 16 or 17 years), patients in this 
age group should be monitored closely during treatment.  
 
Class effects 
 
Opioids may cause orthostatic hypotension. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures. Therefore, opioids 
should be used with caution in patients with head injury, intracranial lesions, other circumstances 
where cerebrospinal pressure may be increased, or history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g. Addison’s disease). 
 
Opioids have been shown to increase intracholedochal pressure, and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with Buvidal. 
 
Buprenorphine should be used cautiously when co-administered with: 
• benzodiazepines: This combination may result in death due to respiratory depression of central 

origin. Therefore, dosages must be closely monitored and this combination must be avoided in 
cases where there is a risk of misuse. Patients should be warned that it is extremely dangerous to 
self-administer non-prescribed benzodiazepines whilst taking this product, and should also be 
cautioned to use benzodiazepines concurrently with this product only as directed by their 
physician (see section 4.4). 

• gabapentinoids: This combination may result in death due to respiratory depression. Therefore, 
dosages must be closely monitored and this combination must be avoided in cases where there 
is a risk of misuse. Patients should be cautioned to use gabapentinoids (such as pregabalin and 
gabapentin) concurrently with this product only as directed by their physician (see section 4.4).  



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• alcoholic drinks or medicinal products containing alcohol as alcohol increases the sedative 
effect of buprenorphine (see section 4.7). 

• other central nervous system depressants: Other opioid derivatives (e.g. methadone, analgesics 
and antitussives); certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, antipsychotics, clonidine and related substances. These 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machinery hazardous (see section 4.7). 

• opioid analgesics: Adequate analgesia may be difficult to achieve when administering a full 
opioid agonist in patients receiving buprenorphine. The potential for overdose also exists with a 
full agonist, especially when attempting to overcome buprenorphine partial agonist effects, or 
when buprenorphine plasma levels are declining (see section 4.4) 

• naltrexone and nalmefene: These are opioid antagonists that can block the pharmacological 
effects of buprenorphine. For opioid-dependent patients currently receiving buprenorphine 
treatment, naltrexone may precipitate a sudden onset of prolonged and intense opioid 
withdrawal symptoms. For patients currently receiving naltrexone treatment, the intended 
therapeutic effects of buprenorphine administration may be blocked by naltrexone. 

• Buprenorphine is metabolised to norbuprenorphine primarily by CYP3A4. The effects on 
buprenorphine exposure in patients treated with Buvidal have not been studied. Interaction with 
co-administered inducers or inhibitors have been established in studies using transmucosal and 
transdermal buprenorphine. Buprenorphine is also metabolised to buprenorphine-3β-
glucuronide by UGT1A1. 
• CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased 

Cmax and AUC of buprenorphine and norbuprenorphine. Buvidal avoids first-pass effects 
and CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or 
azole antifungals such as ketoconazole or itraconazole, or macrolide antibiotics) are 
expected to have less effects on buprenorphine metabolism when co-administered with 
Buvidal as compared to when co-administered with sublingual buprenorphine. When 
switching from sublingual buprenorphine to Buvidal, patients may need to be monitored 
to ensure plasma buprenorphine levels are adequate.  
Patients already on Buvidal who start treatment with CYP3A4 inhibitors should be 
treated with weekly Buvidal and be monitored for signs and symptoms of overtreatment. 
Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4 
inhibitor stops treatment with the CYP3A4 inhibitor, the patient should be monitored for 
symptoms of withdrawal. 

• CYP3A4 inducers may induce the metabolism of buprenorphine resulting in decreased 
buprenorphine levels. Buvidal avoids first-pass effects and CYP3A4 inducers (e.g. 
phenobarbital, carbamazepine, phenytoin or rifampicin) are expected to have less effects 
on buprenorphine metabolism when co-administered with Buvidal as compared to when 
co-administered with sublingual buprenorphine. When switching from sublingual 
buprenorphine to Buvidal, patients may need to be monitored to ensure plasma 
buprenorphine levels are adequate. Patients already on Buvidal who start treatment with 
CYP3A4 inducers should be treated with weekly Buvidal and be monitored for signs and 
symptoms of withdrawal. Conversely, if a patient who is concomitantly treated with 
Buvidal and a CYP3A4 inducer stops treatment with the CYP3A4 inducer, the patient 
should be monitored for symptoms of overtreatment. 

• UGT1A1 inhibitors may affect the systemic exposure of buprenorphine. 
• monoamine oxidase inhibitors (MAOI): Possible exacerbation of the opioids effects, based on 

experience with morphine. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited data from the use of buprenorphine in pregnant women. Animal studies do not 
indicate reproductive toxicity (see section 5.3). Buprenorphine should be used during pregnancy only 
if the potential benefit outweighs the potential risk to the foetus. 



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Towards the end of pregnancy, buprenorphine may induce respiratory depression in the newborn 
infant even after a short period of administration. Long-term administration during the last three 
months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 
tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed from 
several hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days after birth should be 
considered to prevent the risk of respiratory depression or withdrawal syndrome in neonates.  
 
Breast-feeding 
 
Buprenorphine and its metabolites are excreted in human breast milk and Buvidal should be used with 
caution during breast-feeding.  
 
Fertility 
 
There are no or limited data on effects of buprenorphine on human fertility. 
An effect of buprenorphine on fertility in animals has not been seen (see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
Buprenorphine has minor to moderate influence on the ability to drive and use machines when 
administered to opioid-dependent patients. Buprenorphine may cause drowsiness, dizziness or 
impaired thinking, especially during treatment induction and dose adjustment. If used together with 
alcohol or central nervous system depressants, the effect is likely to be more pronounced (see 
sections 4.4. and 4.5).  
 
The patient should be cautioned not to drive or operate hazardous machinery whilst taking this 
medicine until it is known how the patient is affected by the medicine. An individual recommendation 
should be given by the treating healthcare professional.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The adverse reactions most frequently reported for buprenorphine are headache, nausea, hyperhidrosis, 
insomnia, drug withdrawal syndrome and pain. 
 
Tabulated list of adverse reactions 
 
Table 3 presents adverse reactions reported for buprenorphine, including Buvidal. The following terms 
and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 
to < 1/100) and frequency not known (cannot be estimated from available data). 
 

Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Infections and 
infestations 

 Infection 
Influenza 
Pharyngitis 
Rhinitis 

Injection site 
cellulitis  
 

 

Blood and 
lymphatic system 
disorders 

 Lymphadenopathy   

Immune system 
disorders  

 Hypersensitivity   



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Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Metabolism and 
nutrition disorders  

 Decreased appetite   

Psychiatric 
disorders 

Insomnia Anxiety 
Agitation 
Depression 
Hostility 
Nervousness 
Thinking abnormal 
Paranoia 
Medical dependence 

 Hallucinations 
Euphoric mood 

Nervous system 
disorders 

Headache 
 

Somnolence 
Dizziness 
Migraine 
Paraesthesia 
Syncope 
Tremor 
Hypertonia 
Speech disorders 

  

Eye disorders  Lacrimal disorder 
Mydriasis 
Miosis 

  

Ear and labyrinth 
disorders 

 
 

Vertigo  

Cardiac disorders  Palpitations   
Vascular disorders  Vasodilation 

Hypotension 
  

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough 
Dyspnoea 
Yawning 
Asthma 
Bronchitis 

  

Gastrointestinal 
disorders 

Nausea 
 

Constipation 
Vomiting 
Abdominal pain 
Flatulence 
Dyspepsia 
Dry mouth 
Diarrhoea 
Gastrointestinal 
disorder 

  

Hepatobiliary 
disorders 

  Alanine 
aminotransferase 
increased 
Aspartate 
aminotransferase 
increased 
Hepatic enzymes 
increased 

 

Skin and 
subcutaneous tissue 
disorders 

 Rash 
Pruritus 
Urticaria 

Rash macular Erythema 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Back pain 
Myalgia 
Muscle spasms 
Neck pain 
Bone pain 

  

Renal and urinary 
disorders 

   Urinary retention 



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Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Reproductive 
system and breast 
disorders 

 Dysmenorrhoea   

General disorders 
and administration 
site conditions 

Hyperhidrosis 
Drug 
withdrawal 
syndrome 
Pain 
 

Injection site pain 
Injection site pruritus 
Injection site 
erythema 
Injection site swelling 
Injection site reaction 
Injection site 
induration 
Injection site mass 
Oedema peripheral 
Asthenia 
Malaise 
Pyrexia 
Chills 
Neonatal withdrawal 
syndrome 
Chest pain 

Injection site 
inflammation 
Injection site 
bruising 
Injection site 
urticaria 
 

 

Investigations  Abnormal liver 
function tests 

  

Injury, poisoning 
and procedural 
complications 

 
 

Procedural 
dizziness 

 

 
Description of selected adverse reactions 
 
Injection site reactions 
In the double-blind, phase 3 efficacy trial, injection site-related adverse reactions were observed in 
36 (16.9%) of the 213 patients (5% of the administered injections) in the Buvidal treatment group. The 
most common adverse reactions were injection site pain (8.9%), injection site pruritus (6.1%) and 
injection site erythema (4.7%). The injection site reactions were all mild or moderate in severity and 
most events were transient.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medical 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 
 
Symptoms 
 
Respiratory depression, as a result of central nervous system depression, is the primary symptom 
requiring intervention in the case of buprenorphine overdose because it may lead to respiratory arrest 
and death. Preliminary symptoms of overdose may also include excessive sweating, somnolence, 
amblyopia, miosis, hypotension, nausea, vomiting and / or speech disorders. 
 
Treatment 
 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient. Symptomatic treatment of respiratory depression, following standard 
intensive care measures, should be instituted. A patent airway and assisted or controlled ventilation 
must be assured. The patient should be transferred to an environment within which full resuscitation 



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facilities are available. If the patient vomits, precautions must be taken to prevent aspiration. Use of an 
opioid antagonist (i.e. naloxone) is recommended, despite the modest effect it may have in reversing 
the respiratory symptoms of buprenorphine compared with its effects on full agonist opioids. 
 
The long duration of action of buprenorphine and the prolonged release from Buvidal, should be taken 
into consideration when determining length of treatment needed to reverse the effects of an overdose, 
(see section 4.4). Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms. 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in opioid dependence, ATC 
code: N07BC01 
 
Mechanism of action 
 
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ (mu) and κ (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 
properties with the μ-opioid receptors which, over a prolonged period, might minimise the need of 
illicit opioids for patients with opioid dependence. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Clinical efficacy  
 
The efficacy and safety of Buvidal in the treatment of opioid dependence were established in a pivotal 
phase 3, randomised, double-blind, double-dummy, active-controlled, flexible-dose study in patients 
with moderate to severe opioid dependence. In this study, 428 patients were randomised to one of two 
treatment groups. Patients in the Buvidal group (n = 213) received weekly injections (16 mg to 32 mg) 
during the first 12 weeks followed by monthly injections (64 mg to 160 mg) during the last 12 weeks, 
plus daily doses of sublingual placebo tablets during the complete treatment period. Patients in the 
sublingual buprenorphine/naloxone group (n = 215) received weekly placebo injections during the first 
12 weeks and monthly placebo injections during the last 12 weeks, plus daily sublingual 
buprenorphine/naloxone tablets during the complete treatment period (8 mg to 24 mg during the first 
12 weeks and 8 mg to 32 mg during the last 12 weeks). During the 12 weeks with monthly injections, 
patients in both groups could receive one additional 8 mg weekly Buvidal dose per month, if needed. 
Patients attended 12 weekly visits during the first 12 weeks and 6 visits during the last 12 weeks 
(3 scheduled monthly visits and 3 random urine toxicology visits). At each visit, efficacy and safety 
outcome measures were assessed.  
Of the 428 randomised patients, 69.0% (147/213) of the patients in the Buvidal treatment group and 
72.6% (156/215) of the patients in the sublingual buprenorphine/naloxone treatment group completed 
the 24-week treatment period.  
The study met the primary endpoint of non-inferiority in mean percentage of urine samples negative 
for illicit opioids during treatment weeks 1 to 24 for the Buvidal group compared with the sublingual 
buprenorphine/naloxone group (Table 4).  
Superiority of Buvidal versus sublingual buprenorphine/naloxone was met (pre-specified test order) 
for the secondary endpoint cumulative distribution function (CDF) for percentage of opioid-negative 
urine samples during treatment weeks 4 to 24 (Table 4).  
 



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Table 4. Efficacy variables in a pivotal phase 3, randomised, double-blind, double-
dummy, active-controlled, flexible-dose study in patients with moderate to 
severe opioid dependence 

Efficacy variable Statistic Buvidal SL BPN/NX 
Treatment 
difference (%)a 
(95% CI) 

P-value 

Percentage of urine 
samples negative for illicit 
opioids 

N 213 215   
LS mean 
(%) (SE)  35.1 (2.48) 28.4 (2.47) 6.7 <0.001 

95% CI 30.3 - 40.0 23.5 - 33.3 -0.1 - 13.6  

CDF of percentage of urine 
samples negative for illicit 
opioids over weeks 4-24 

N 213 215   

Median 26.7 6.7 - 0.008b 

CDF = cumulative distribution function, CI = confidence interval, LS = least squares; SE = standard 
error, SL BPN/NX = sublingual buprenorphine/naloxone 
a Difference = Buvidal – SL BPN/NX. 
b The p-value was for superiority  
 
A long-term, open-label, phase 3 safety study with flexible dosing of weekly and monthly Buvidal for 
48 weeks was conducted. The study enrolled a total of 227 patients with moderate to severe opioid 
dependence, of which 190 patients were switched from sublingual buprenorphine (with or without 
naloxone), and 37 patients were new to buprenorphine treatment. During the 48-week treatment 
period, patients could be transitioned between weekly and monthly injections with Buvidal and 
between doses (8 mg to 32 mg weekly Buvidal and 64 mg to 160 mg monthly Buvidal) according to 
the physician’s clinical judgement.  
For patients who were switched from sublingual buprenorphine, the percentage of patients with illicit 
opioid-negative urine samples was 78.8% at baseline and 84.0% at the end of the 48-week treatment 
period. For the new-to-treatment patients, the percentage of patients with illicit opioid-negative urine 
samples was 0.0% at baseline and 63.0% at the end of the 48-week treatment period. Overall, 
156 patients (68.7%) completed the 48-week treatment period. 
 
5.2 Pharmacokinetic properties 
 
Weekly Buvidal 
 
Absorption 
 
After injection, the buprenorphine plasma concentration increases with a median time to maximum 
plasma concentration (tmax) of about 24 hours. Buvidal has complete absolute bioavailability. Steady-
state exposure is reached at the fourth weekly dose.  
 
Dose-proportional increases in exposure are observed in the dose interval 8 mg to 32 mg. 
 
Distribution 
 
The apparent volume of distribution for buprenorphine is approximately 1900 L. Buprenorphine is 
approximately 96% protein-bound, primarily to alpha and beta globulin.  
 
Biotransformation and elimination 
 
Buprenorphine is oxidatively metabolised by 14-N-dealkylation to N-desalkyl-buprenorphine (also 
known as norbuprenorphine) via cytochrome P450 CYP3A4 and by glucuroconjungation of the parent 
molecule and the dealkylated metabolite. Norbuprenorphine is a µ-opioid agonist with weak intrinsic 
activity.  



14 

 
Subcutaneous administration of Buvidal results in significantly lower plasma concentrations of 
norbuprenorphine metabolite compared to administration of sublingual buprenorphine, due to 
avoidance of first-pass metabolism. 
 
Elimination of buprenorphine from Buvidal is release-rate limited with a terminal half-life ranging 
from 3 to 5 days.  
 
Buprenorphine is primarily eliminated in the faeces by biliary excretion of the glucuroconjugated 
metabolites (70%), the remainder being eliminated in the urine. Total clearance of buprenorphine is 
approximately 68 L/h. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients (> 65 years) are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (≈ 30%) in the overall clearance of buprenorphine. No 
dose modification based on renal function is required, but caution is recommended when dosing 
subjects with severe renal impairment (see sections 4.2 and 4.4). 
 
Hepatic impairment 
Table 5 summarises the results of a clinical study in which exposure to buprenorphine was determined 
following administration of a buprenorphine/naloxone 2.0/0.5 mg sublingual tablet in healthy subjects 
and in subjects with different degrees of hepatic impairment. 
 

Table 5.  Effect of hepatic impairment (change relative to healthy subjects) on 
pharmacokinetic parameters of buprenorphine following sublingual 
buprenorphine/naloxone administration (2.0/0.5 mg) in healthy subjects, and in 
subjects with varied degrees of hepatic impairment 

Pharmacokinetic 
Parameter 

mild hepatic 
impairment 
(Child-Pugh Class A) 
(n=9) 

moderate hepatic 
impairment 
(Child-Pugh Class B) 
(n=8) 

severe hepatic 
impairment 
(Child-Pugh Class C) 
(n=8) 

Buprenorphine 
Cmax 1.2-fold increase  1.1-fold increase  1.7-fold increase  
AUClast Similar to control  1.6-fold increase  2.8-fold increase  

 
Overall, buprenorphine plasma exposure increased approximately 3-fold in subjects with severely 
impaired hepatic function (see sections 4.2, 4.3 and 4.4). 
 
Paediatric population 
No pharmacokinetic data in paediatrics (less than 18 years) are available. Simulated buprenorphine 
exposure data in adolescents aged 16 years show lower Cmax and AUC compared to observed values in 
adults for weekly and monthly Buvidal. 
 
5.3 Preclinical safety data 
 
Acute toxicity of buprenorphine was determined in mice and rats following oral and parenteral 
(intravenous, intraperitoneal) administration. Undesirable effects were based on the known 
pharmacological activity of buprenorphine. 
 
Buprenorphine showed low tissue and biochemical toxicities when beagles were dosed subcutaneously 
for one month, rhesus monkeys orally for one month and rats and baboons intramuscularly for six 
months. 
 



15 

Teratology and reproduction toxicity studies in rats and rabbits by intramuscular administration 
concluded that buprenorphine is not embryotoxic or teratogenic and has no marked effects on weaning 
potential. In rats there were no adverse effects on fertility of general reproductive function. 
Chronic toxicity studies in rat and dog of the vehicle used for Buvidal revealed no special hazard for 
humans. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Buvidal 8 mg, 16 mg, 24 mg, 32 mg 
 
Soybean phosphatidylcholine 
Glycerol dioleate 
Ethanol anhydrous 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products.  
 
6.3 Shelf life 
 
30 months 
 
6.4 Special precautions for storage 
 
Do not refrigerate or freeze. 
 
6.5 Nature and contents of container  
 
A 1 mL pre-filled syringe (glass, Type I) with plunger stopper (fluoropolymer-coated bromobutyl 
rubber) with needle (½-inch, 23 gauge, 12 mm) and needle shield (styrene butadiene rubber). The pre-
filled syringe is assembled in a safety device for post-injection needlestick prevention. The needle 
shield of the safety syringe may contain rubber latex that may cause allergic reactions in latex-
sensitive individuals. 
 
Pack sizes 
 
Pack contains 1 pre-filled syringe with stopper, needle, needle shield, safety device and 1 plunger rod. 
 
6.6 Special precautions for disposal and other handling 
 
Important information 
 
• Administration should be made into the subcutaneous tissue 
• Intravascular, intramuscular and intradermal administration must be avoided. 
• Must not be used if the safety syringe is broken or the packaging is damaged. 
• The needle shield of the syringe may contain rubber latex that may cause allergic reactions in 

latex sensitive individuals. 
• Handle the safety syringe carefully to avoid a needle stick. The safety syringe includes a needle 

protection safety device that will activate at the end of the injection. Do not uncap the safety 
syringe until you are ready to inject. Once uncapped, never try to recap the needle. 

• Dispose of the used safety syringe right away after use. Do not re-use the safety syringe. 
 



16 

Before administration 
 
Safety syringe parts: 

 
Figure 1: Safety Syringe: Before Use 

a) Needle shield, b) Syringe Guard Body, 
c) Syringe Guard Wings, d) Plunger,  
e) Plunger Head 

Safety Syringe: After Use 
(With needle protection mechanism activated) 

 
Please note that the smallest injection volume is barely visible in the viewing window as the 
spring of the safety device is “covering” part of the glass cylinder close to the needle. 

 
Administration (see also section 4.2) 
 
- Take the syringe out of the cardboard box: pick up the syringe by the syringe guard body. 
- While holding the syringe by the needle shield, insert the plunger rod into the plunger stopper 

by gently rotating the plunger rod clockwise until secured (see Figure 2). 
 

 
Figure 2: Before After 

 
- Inspect the safety syringe closely: 

- Do not use the safety syringe after the expiration date shown on the cardboard box or on 
the syringe label. 

- A small air bubble may be seen, which is normal. 
- The liquid should be clear. Do not use the safety syringe if the liquid contains visible 

particles or is cloudy. 
 
- Choose the injection site. Injections should be rotated between sites in the buttock, thigh, 

abdomen, or upper arm (see Figure 3) with a minimum of 8 weeks before re-injecting a 
previously used injection site. Injections on the waistline or within 5 cm of the navel should be 
avoided. 



17 

 

 
Figure 3: 
 
- Put on gloves and clean the injection site with a circular motion using an alcohol wipe (not 

provided in the pack). Do not touch the cleaned area again before injecting. 
- While holding the safety syringe by the syringe guard body as shown (see Figure 4), carefully 

pull the needle shield straight off. Immediately dispose of the needle shield (never try to recap 
the needle). A drop of liquid may be seen at the end of the needle. This is normal. 

 

 
Figure 4:  
 
- Pinch the skin at the injection site between the thumb and finger as shown (see Figure 5). 
- Hold the safety syringe as shown and smoothly insert the needle at an angle of approximately 

90° (see Figure 5). Push the needle all the way in. 

 
Figure 5:  
 
- While holding the syringe as shown (see Figure 6), slowly depress the plunger until the plunger 

head latches between the syringe guard wings and all the solution is injected.  



18 

 

 
Figure 6:  
 
- Gently pull the needle out of the skin. It is recommended that the plunger is kept fully depressed 

while the needle is carefully lifted straight out from the injection site (see Figure 7). 
 

 
Figure 7:  
 
- As soon as the needle has been completely removed from the skin, slowly take the thumb off 

the plunger and allow the syringe guard to automatically cover the exposed needle (see 
Figure 8). There may be a small amount of blood at the injection site, if required wipe with a 
cotton ball or gauze.  

 
Figure 8: 
 
Disposing of the syringe 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 



19 

7. MARKETING AUTHORISATION HOLDER 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
Phone: +800 2577 2577 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Buvidal prolonged-release solution for injection (weekly) 
EU/1/18/1336/001 [8 mg buprenorphine/0.16 mL] 
EU/1/18/1336/002 [16 mg buprenorphine/0.32 mL] 
EU/1/18/1336/003 [24 mg buprenorphine 0.48 mL] 
EU/1/18/1336/004 [32 mg buprenorphine/0.64 mL] 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  
20 November 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 
  



20 

1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 64 mg prolonged-release solution for injection  
Buvidal 96 mg prolonged-release solution for injection  
Buvidal 128 mg prolonged-release solution for injection  
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
64 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 64 mg buprenorphine  
 
96 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 96 mg buprenorphine  
 
128 mg prolonged-release solution for injection  
 
Each pre-filled syringe contains 128 mg buprenorphine  
 
For the full list of excipients, see section 6.1.  
 
 
3. PHARMACEUTICAL FORM 
 
Prolonged-release solution for injection. 
Yellowish to yellow clear liquid. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
Treatment of opioid dependence within a framework of medical, social and psychological treatment. 
Treatment is intended for use in adults and adolescents aged 16 years or over. 
 
4.2 Posology and method of administration 
 
Administration of Buvidal is restricted to healthcare professionals. Appropriate precautions, such as to 
conduct patient follow-up visits with clinical monitoring according to the patient's needs, should be 
taken when prescribing and dispensing buprenorphine. Take-home use or self-administration of the 
product by patients is not allowed. 
 
Precautions to be taken before initiation of treatment  
 
To avoid precipitating symptoms of withdrawal, treatment with Buvidal should be started when 
objective and clear signs of mild to moderate withdrawal are evident (see section 4.4). Consideration 
should be given to the types of opioid used (that is long- or short-acting opioid), time since last opioid 
use and the degree of opioid dependence. 
 
• For patients using heroin or short-acting opioids, the initial dose of Buvidal must not be 

administered until at least 6 hours after the patient last used opioids. 
• For patients receiving methadone, the methadone dose should be reduced to a maximum of 

30 mg/day before starting treatment with Buvidal which should not be administered until at 
least 24 hours after the patient last received a methadone dose. Buvidal may trigger withdrawal 
symptoms in methadone-dependent patients. 



21 

 
Posology 
 
Initiation of treatment in patients not already receiving buprenorphine 
Patients not previously exposed to buprenorphine should receive a sublingual buprenorphine 4 mg 
dose and be observed for an hour before the first administration of weekly Buvidal to confirm 
tolerability to buprenorphine. 
 
The recommended starting dose of Buvidal is 16 mg, with one or two additional 8 mg doses at least 
1 day apart, to a target dose of 24 mg or 32 mg during the first treatment week. The recommended 
dose for the second treatment week is the total dose administered during the week of initiation.  
 
Treatment with monthly Buvidal can be started after treatment initiation with weekly Buvidal, in 
accordance with the dose conversion in Table 2 and once patients have been stabilised on weekly 
treatment (four weeks or more, where practical).  
 
Switching from sublingual buprenorphine products to Buvidal  
Patients treated with sublingual buprenorphine may be switched directly to weekly or monthly 
Buvidal, starting on the day after the last daily buprenorphine sublingual treatment dose in accordance 
with the dosing recommendations in Table 1. Closer monitoring of patients is recommended during 
the dosing period after the switch. 
 

Table 1. Conventional sublingual buprenorphine daily treatment doses and 
recommended corresponding doses of weekly and monthly Buvidal 

Dose of daily sublingual 
buprenorphine 

Dose of weekly Buvidal Dose of monthly Buvidal 

2-6 mg 8 mg   
8-10 mg  16 mg  64 mg  
12-16 mg  24 mg  96 mg  
18-24 mg  32 mg  128 mg  

 
The dose of buprenorphine in mg can differ between sublingual products, which needs to be taken into 
consideration on a product-by-product basis. The pharmacokinetic properties of Buvidal are described 
in section 5.2. 
 
Maintenance treatment and dose adjustments 
Buvidal can be administered weekly or monthly. Doses may be increased or decreased and patients 
can be switched between weekly and monthly products according to individual patient’s needs and 
treating physician’s clinical judgement as per recommendations in Table 2. Following switching, 
patients may need closer monitoring. Assessment of long-term treatment is based on 48-week data. 
 
Table 2.  Recommended dose conversion when switching from weekly to monthly dosing 

or from monthly to weekly dosing 
Weekly dose of Buvidal Monthly dose of Buvidal 
16 mg 64 mg 
24 mg 96 mg 
32 mg 128 mg 

 
Supplemental dosing 
A maximum of one supplemental Buvidal 8 mg dose may be administered at an unscheduled visit 
between regular weekly and monthly doses, based on individual patient’s temporary needs. 
The maximum dose per week for patients who are on weekly Buvidal treatment is 32 mg with an 
additional 8 mg dose. The maximum dose per month for patients who are on monthly Buvidal 
treatment is 128 mg with an additional 8 mg dose.  
 



22 

Missed doses 
To avoid missed doses, the weekly dose may be administered up to 2 days before or after the weekly 
time point, and the monthly dose may be administered up to 1 week before or after the monthly time 
point. 
 
If a dose is missed, the next dose should be administered as soon as practically possible.  
 
Termination of treatment 
If Buvidal treatment is discontinued, its prolonged-release characteristics and any withdrawal 
symptoms experienced by the patient must be considered, see section 4.4. If the patient is switched to 
treatment with sublingual buprenorphine, this should be done one week after the last weekly dose or 
one month after the last monthly dose of Buvidal according to the recommendations in Table 1. 
 
Special populations 
 
Elderly 
The efficacy and safety of buprenorphine in elderly patients > 65 years have not been established. No 
recommendation on posology can be made. 
 
In general, recommended dosing for elderly patients with normal renal function is the same as for 
younger adult patients with normal renal function. However, because elderly patients may have 
diminished renal/hepatic function, dose adjustment may be necessary (see Hepatic impairment and 
Renal impairment below). 
 
Hepatic impairment 
Buprenorphine should be used with caution in patients with moderate hepatic impairment (see 
section 5.2). In patients with severe hepatic impairment, the use of buprenorphine is contraindicated 
(see section 4.3). 
 
Renal impairment 
Modification of the buprenorphine dose is not required for patients with renal impairment. Caution is 
recommended when dosing patients with severe renal impairment (creatinine clearance < 30 ml/min) 
(see sections 4.4 and 5.2). 
 
Paediatric population  
The safety and efficacy buprenorphine in children and adolescents below 16 years of age have not 
been established (see section 4.4). No data are available. 
 
Method of administration 
 
Buvidal is intended for subcutaneous administration only. It should be injected slowly and completely 
into the subcutaneous tissue of different areas (buttock, thigh, abdomen, or upper arm), provided there 
is enough subcutaneous tissue. Each area can have multiple injection sites. Injection sites should be 
rotated for both weekly and monthly injections. A minimum of 8 weeks should be left before re-
injecting a previously used injection site with the weekly dose. There is no clinical data supporting 
reinjection of the monthly dose into the same site. This is unlikely to be a safety concern. The decision 
to reinject at the same site should also be guided by the attending physicians´ clinical judgement. 
Administered dose should be as a single injection and not divided. The dose must not be administered 
intravascularly (intravenously), intramuscularly or intradermally (into the skin) (see section 4.4). See 
section 6.6 for administration instructions. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 
Severe respiratory insufficiency 
Severe hepatic impairment 
Acute alcoholism or delirium tremens 



23 

 
4.4 Special warnings and precautions for use 
 
Administration 
 
Care must be taken to avoid inadvertent injection of Buvidal. The dose must not be administered 
intravascularly (intravenously), intramuscularly or intradermally.  
 
Intravascular such as intravenous injection would present a risk of serious harm as Buvidal forms a 
solid mass upon contact with body fluids, which potentially could cause blood vessel injury, 
occlusion, or thromboembolic events. 
 
To minimise the risk of misuse, abuse and diversion, appropriate precautions should be taken when 
prescribing and dispensing buprenorphine. Healthcare professionals should administer Buvidal 
directly to the patient. Take-home use or self-administration of the product by patients is not allowed. 
Any attempts to remove the depot should be monitored throughout treatment. 
 
Prolonged-release properties 
 
The prolonged-release properties of the product should be considered during treatment including 
initiation and termination. In particular, patients with concomitant medicinal products and/or co-
morbidities, should be monitored for signs and symptoms of toxicity, overdose or withdrawal caused 
by increased or decreased levels of buprenorphine. 
For pharmacokinetic properties, see section 5.2 and for treatment termination, see section 4.2. 
 
Respiratory depression 
 
A number of cases of death due to respiratory depression have been reported for patients being treated 
with buprenorphine, particularly when used in combination with benzodiazepines (see section 4.5) or 
when buprenorphine was not used according to prescribing information. Deaths have also been 
reported in association with concomitant administration of buprenorphine and other depressants such 
as alcohol, gabapentinoids (such as pregabalin and gabapentin) (see section 4.5) or other opioids.  
Buprenorphine should be used with care in patients with respiratory insufficiency (e.g. chronic 
obstructive pulmonary disease, asthma, cor pulmonale, decreased respiratory reserve, hypoxia, 
hypercapnia, pre-existing respiratory depression or kyphoscoliosis). 
 
Buprenorphine may cause severe, possibly fatal, respiratory depression in children and non-opioid 
dependent persons who accidentally or deliberately use it.  
 
CNS depression 
 
Buprenorphine may cause drowsiness particularly when taken together with alcohol or central nervous 
system depressants such as benzodiazepines, tranquilisers, sedatives, gabapentinoids or hypnotics (see 
sections 4.5 and 4.7). 
 
Dependence 
 
Buprenorphine is a partial agonist at the mu-opiate receptor and chronic administration can produce 
opioid dependence.  
 
Hepatitis and hepatic events 
 
Baseline liver function tests and documentation of viral hepatitis status are recommended prior to 
starting therapy. Patients who are positive for viral hepatitis, on certain concomitant medicinal 
products (see section 4.5) and/or who have existing liver dysfunction are at greater risk of liver injury. 
Regular monitoring of the liver function is recommended. 



24 

Cases of acute hepatic injury have been reported in opioid-dependent patients both in clinical studies 
and in post-marketing adverse reaction reports with medicinal products containing buprenorphine. The 
spectrum of abnormalities ranges from transient asymptomatic elevations in hepatic transaminases to 
case reports of cytolytic hepatitis, hepatic failure, hepatic necrosis, hepatorenal syndrome, hepatic 
encephalopathy and death. In many cases, the presence of pre-existing liver enzyme abnormalities, 
genetic disease, infection with hepatitis B or hepatitis C virus, alcohol abuse, anorexia, concomitant 
use of other potentially hepatotoxic medicinal products and ongoing injecting drug use may have a 
causative or contributory role. These underlying factors must be taken into consideration before 
prescribing buprenorphine and during treatment. When a hepatic event is suspected, further biological 
and aetiological evaluation is required. Depending on the findings, Buvidal may be discontinued. 
Monitoring beyond the weekly and monthly treatment period may be needed. If treatment is 
continued, hepatic function should be monitored closely. 
 
Precipitation of opioid withdrawal syndrome 
 
When initiating treatment with buprenorphine, it is important to be aware of the partial agonist profile 
of buprenorphine. Buprenorphine products have caused precipitated withdrawal symptoms in opioid-
dependent patients when administered before the agonist effects resulting from recent opioid use or 
misuse have subsided. To avoid precipitated withdrawal, induction must be undertaken when objective 
signs and symptoms of mild to moderate withdrawal are evident (see section 4.2).  
Discontinuation of treatment may result in a withdrawal syndrome that may be delayed in onset. 
 
Hepatic impairment 
 
Buprenorphine is extensively metabolised in the liver. Patients with moderate hepatic impairment 
should be monitored for signs and symptoms of precipitated opioid withdrawal, toxicity or overdose 
caused by increased levels of buprenorphine. Buprenorphine should be used with caution in patients 
with moderate hepatic impairment (see sections 4.2 and 5.2). Hepatic function should be monitored 
regularly whilst on treatment. The use of buprenorphine is contraindicated in patients with severe 
hepatic impairment (see section 4.3). 
 
Renal impairment 
 
Metabolites of buprenorphine accumulate in patients with renal failure. Caution is recommended when 
dosing patients with severe renal impairment (creatinine clearance < 30 ml/min), see sections 4.2 and 
5.2. 
 
QT prolongation 
 
Caution should be exercised when co-administering Buvidal with other medicinal products that 
prolong the QT interval and in patients with a history of long QT syndrome or other risk factors for 
QT prolongation. 
 
Acute pain management 
 
For management of acute pain during continued use of Buvidal, a combination of use of opioids with 
high mu-opioid receptor affinity (e.g. fentanyl), non-opioid analgesics and regional anaesthesia might 
be necessary. Titration of oral or intravenous short-acting opioid pain medicinal products (immediate-
release morphine, oxycodone or fentanyl) to the desired analgesic effect in patients treated with 
Buvidal might require higher doses. Patients should be monitored during treatment. 
 
Use in children and adolescents 
 
The safety and efficacy of buprenorphine in children below the age of 16 years have not been 
established (see section 4.2). Due to limited data in adolescents (aged 16 or 17 years), patients in this 
age group should be monitored closely during treatment.  
 



25 

Class effects 
 
Opioids may cause orthostatic hypotension. 
 
Opioids may elevate cerebrospinal fluid pressure, which may cause seizures. Therefore, opioids 
should be used with caution in patients with head injury, intracranial lesions, other circumstances 
where cerebrospinal pressure may be increased, or history of seizure. 
 
Opioids should be used with caution in patients with hypotension, prostatic hypertrophy or urethral 
stenosis. 
 
Opioid-induced miosis, changes in the level of consciousness or changes in the perception of pain as a 
symptom of disease may interfere with patient evaluation or obscure the diagnosis or clinical course of 
concomitant disease. 
 
Opioids should be used with caution in patients with myxoedema, hypothyroidism, or adrenal cortical 
insufficiency (e.g. Addison’s disease). 
 
Opioids have been shown to increase intracholedochal pressure, and should be used with caution in 
patients with dysfunction of the biliary tract. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No interaction studies have been performed with Buvidal. 
 
Buprenorphine should be used cautiously when co-administered with: 
• benzodiazepines: This combination may result in death due to respiratory depression of central 

origin. Therefore, dosages must be closely monitored and this combination must be avoided in 
cases where there is a risk of misuse. Patients should be warned that it is extremely dangerous to 
self-administer non-prescribed benzodiazepines whilst taking this product, and should also be 
cautioned to use benzodiazepines concurrently with this product only as directed by their 
physician (see section 4.4). 

• gabapentinoids: This combination may result in death due to respiratory depression. Therefore, 
dosages must be closely monitored and this combination must be avoided in cases where there 
is a risk of misuse. Patients should be cautioned to use gabapentinoids (such as pregabalin and 
gabapentin) concurrently with this product only as directed by their physician (see section 4.4).  

• alcoholic drinks or medicinal products containing alcohol as alcohol increases the sedative 
effect of buprenorphine (see section 4.7). 

• other central nervous system depressants: Other opioid derivatives (e.g. methadone, analgesics 
and antitussives); certain antidepressants, sedative H1-receptor antagonists, barbiturates, 
anxiolytics other than benzodiazepines, antipsychotics, clonidine and related substances. These 
combinations increase central nervous system depression. The reduced level of alertness can 
make driving and using machinery hazardous (see section 4.7). 

• opioid analgesics: Adequate analgesia may be difficult to achieve when administering a full 
opioid agonist in patients receiving buprenorphine. The potential for overdose also exists with a 
full agonist, especially when attempting to overcome buprenorphine partial agonist effects, or 
when buprenorphine plasma levels are declining (see section 4.4) 

• naltrexone and nalmefene: These are opioid antagonists that can block the pharmacological 
effects of buprenorphine. For opioid-dependent patients currently receiving buprenorphine 
treatment, naltrexone may precipitate a sudden onset of prolonged and intense opioid 
withdrawal symptoms. For patients currently receiving naltrexone treatment, the intended 
therapeutic effects of buprenorphine administration may be blocked by naltrexone. 

• Buprenorphine is metabolised to norbuprenorphine primarily by CYP3A4. The effects on 
buprenorphine exposure in patients treated with Buvidal have not been studied. Interaction with 
co-administered inducers or inhibitors have been established in studies using transmucosal and 
transdermal buprenorphine. Buprenorphine is also metabolised to buprenorphine-3β-
glucuronide by UGT1A1. 



26 

• CYP3A4 inhibitors may inhibit the metabolism of buprenorphine resulting in increased 
Cmax and AUC of buprenorphine and norbuprenorphine. Buvidal avoids first-pass effects 
and CYP3A4 inhibitors (e.g. protease inhibitors like ritonavir, nelfinavir or indinavir, or 
azole antifungals such as ketoconazole or itraconazole, or macrolide antibiotics) are 
expected to have less effects on buprenorphine metabolism when co-administered with 
Buvidal as compared to when co-administered with sublingual buprenorphine. When 
switching from sublingual buprenorphine to Buvidal, patients may need to be monitored 
to ensure plasma buprenorphine levels are adequate.  
Patients already on Buvidal who start treatment with CYP3A4 inhibitors should be 
treated with weekly Buvidal and be monitored for signs and symptoms of overtreatment. 
Conversely, if a patient who is concomitantly treated with Buvidal and a CYP3A4 
inhibitor stops treatment with the CYP3A4 inhibitor, the patient should be monitored for 
symptoms of withdrawal. 

• CYP3A4 inducers may induce the metabolism of buprenorphine resulting in decreased 
buprenorphine levels. Buvidal avoids first-pass effects and CYP3A4 inducers (e.g. 
phenobarbital, carbamazepine, phenytoin or rifampicin) are expected to have less effects 
on buprenorphine metabolism when co-administered with Buvidal as compared to when 
co-administered with sublingual buprenorphine. When switching from sublingual 
buprenorphine to Buvidal, patients may need to be monitored to ensure plasma 
buprenorphine levels are adequate. Patients already on Buvidal who start treatment with 
CYP3A4 inducers should be treated with weekly Buvidal and be monitored for signs and 
symptoms of withdrawal. Conversely, if a patient who is concomitantly treated with 
Buvidal and a CYP3A4 inducer stops treatment with the CYP3A4 inducer, the patient 
should be monitored for symptoms of overtreatment. 

• UGT1A1 inhibitors may affect the systemic exposure of buprenorphine. 
• monoamine oxidase inhibitors (MAOI): Possible exacerbation of the opioids effects, based on 

experience with morphine. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There are no or limited data from the use of buprenorphine in pregnant women. Animal studies do not 
indicate reproductive toxicity (see section 5.3). Buprenorphine should be used during pregnancy only 
if the potential benefit outweighs the potential risk to the foetus. 
 
Towards the end of pregnancy, buprenorphine may induce respiratory depression in the newborn 
infant even after a short period of administration. Long-term administration during the last three 
months of pregnancy may cause a withdrawal syndrome in the neonate (e.g. hypertonia, neonatal 
tremor, neonatal agitation, myoclonus or convulsions). The syndrome is generally delayed from 
several hours to several days after birth. 
 
Due to the long half-life of buprenorphine, neonatal monitoring for several days after birth should be 
considered to prevent the risk of respiratory depression or withdrawal syndrome in neonates.  
 
Breast-feeding 
 
Buprenorphine and its metabolites are excreted in human breast milk and Buvidal should be used with 
caution during breast-feeding.  
 
Fertility 
 
There are no or limited data on effects of buprenorphine on human fertility. 
An effect of buprenorphine on fertility in animals has not been seen (see section 5.3). 
 



27 

4.7 Effects on ability to drive and use machines 
 
Buprenorphine has minor to moderate influence on the ability to drive and use machines when 
administered to opioid-dependent patients. Buprenorphine may cause drowsiness, dizziness or 
impaired thinking, especially during treatment induction and dose adjustment. If used together with 
alcohol or central nervous system depressants, the effect is likely to be more pronounced (see 
sections 4.4. and 4.5).  
 
The patient should be cautioned not to drive or operate hazardous machinery whilst taking this 
medicine until it is known how the patient is affected by the medicine. An individual recommendation 
should be given by the treating healthcare professional.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
The adverse reactions most frequently reported for buprenorphine are headache, nausea, hyperhidrosis, 
insomnia, drug withdrawal syndrome and pain. 
 
Tabulated list of adverse reactions 
 
Table 3 presents adverse reactions reported for buprenorphine, including Buvidal. The following terms 
and frequencies are applied: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 
to < 1/100) and frequency not known (cannot be estimated from available data). 
 

Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Infections and 
infestations 

 Infection 
Influenza 
Pharyngitis 
Rhinitis 

Injection site 
cellulitis  
 

 

Blood and 
lymphatic system 
disorders 

 Lymphadenopathy   

Immune system 
disorders  

 Hypersensitivity   

Metabolism and 
nutrition disorders  

 Decreased appetite   

Psychiatric 
disorders 

Insomnia Anxiety 
Agitation 
Depression 
Hostility 
Nervousness 
Thinking abnormal 
Paranoia 
Medical dependence 

 Hallucinations 
Euphoric mood 

Nervous system 
disorders 

Headache 
 

Somnolence 
Dizziness 
Migraine 
Paraesthesia 
Syncope 
Tremor 
Hypertonia 
Speech disorders 

  

Eye disorders  Lacrimal disorder 
Mydriasis 
Miosis 

  

Ear and labyrinth 
disorders 

 
 

Vertigo  



28 

Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Cardiac disorders  Palpitations   
Vascular disorders  Vasodilation 

Hypotension 
  

Respiratory, 
thoracic and 
mediastinal 
disorders 

 Cough 
Dyspnoea 
Yawning 
Asthma 
Bronchitis 

  

Gastrointestinal 
disorders 

Nausea 
 

Constipation 
Vomiting 
Abdominal pain 
Flatulence 
Dyspepsia 
Dry mouth 
Diarrhoea 
Gastrointestinal 
disorder 

  

Hepatobiliary 
disorders 

  Alanine 
aminotransferase 
increased 
Aspartate 
aminotransferase 
increased 
Hepatic enzymes 
increased 

 

Skin and 
subcutaneous tissue 
disorders 

 Rash 
Pruritus 
Urticaria 

Rash macular Erythema 

Musculoskeletal and 
connective tissue 
disorders 

 Arthralgia 
Back pain 
Myalgia 
Muscle spasms 
Neck pain 
Bone pain 

  

Renal and urinary 
disorders 

   Urinary retention 

Reproductive 
system and breast 
disorders 

 Dysmenorrhoea   

General disorders 
and administration 
site conditions 

Hyperhidrosis 
Drug 
withdrawal 
syndrome 
Pain 
 

Injection site pain 
Injection site pruritus 
Injection site 
erythema 
Injection site swelling 
Injection site reaction 
Injection site 
induration 
Injection site mass 
Oedema peripheral 
Asthenia 
Malaise 
Pyrexia 
Chills 
Neonatal withdrawal 
syndrome 
Chest pain 

Injection site 
inflammation 
Injection site 
bruising 
Injection site 
urticaria 
 

 

Investigations  Abnormal liver 
function tests 

  



29 

Table 3. Adverse reactions listed by body system 
System Organ Class Very common 

 
Common 
 

Uncommon 
 

Not known 

Injury, poisoning 
and procedural 
complications 

 
 

Procedural 
dizziness 

 

 
Description of selected adverse reactions 
 
Injection site reactions 
In the double-blind, phase 3 efficacy trial, injection site-related adverse reactions were observed in 
36 (16.9%) of the 213 patients (5% of the administered injections) in the Buvidal treatment group. The 
most common adverse reactions were injection site pain (8.9%), injection site pruritus (6.1%) and 
injection site erythema (4.7%). The injection site reactions were all mild or moderate in severity and 
most events were transient.  
 
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medical 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 
 
Symptoms 
 
Respiratory depression, as a result of central nervous system depression, is the primary symptom 
requiring intervention in the case of buprenorphine overdose because it may lead to respiratory arrest 
and death. Preliminary symptoms of overdose may also include excessive sweating, somnolence, 
amblyopia, miosis, hypotension, nausea, vomiting and / or speech disorders. 
 
Treatment 
 
General supportive measures should be instituted, including close monitoring of respiratory and 
cardiac status of the patient. Symptomatic treatment of respiratory depression, following standard 
intensive care measures, should be instituted. A patent airway and assisted or controlled ventilation 
must be assured. The patient should be transferred to an environment within which full resuscitation 
facilities are available. If the patient vomits, precautions must be taken to prevent aspiration. Use of an 
opioid antagonist (i.e. naloxone) is recommended, despite the modest effect it may have in reversing 
the respiratory symptoms of buprenorphine compared with its effects on full agonist opioids. 
 
The long duration of action of buprenorphine and the prolonged release from Buvidal, should be taken 
into consideration when determining length of treatment needed to reverse the effects of an overdose, 
(see section 4.4). Naloxone can be cleared more rapidly than buprenorphine, allowing for a return of 
previously controlled buprenorphine overdose symptoms. 
 
5. PHARMACOLOGICAL PROPERTIES 
 
5.1 Pharmacodynamic properties 
 
Pharmacotherapeutic group: Other nervous system drugs, drugs used in opioid dependence, ATC 
code: N07BC01 
 
Mechanism of action 
 
Buprenorphine is an opioid partial agonist/antagonist which binds to the μ (mu) and κ (kappa) opioid 
receptors of the brain. Its activity in opioid maintenance treatment is attributed to its slowly reversible 



30 

properties with the μ-opioid receptors which, over a prolonged period, might minimise the need of 
illicit opioids for patients with opioid dependence. 
 
Opioid agonist ceiling effects were observed during clinical pharmacology studies in opioid-dependent 
persons. 
 
Clinical efficacy  
 
The efficacy and safety of Buvidal in the treatment of opioid dependence were established in a pivotal 
phase 3, randomised, double-blind, double-dummy, active-controlled, flexible-dose study in patients 
with moderate to severe opioid dependence. In this study, 428 patients were randomised to one of two 
treatment groups. Patients in the Buvidal group (n = 213) received weekly injections (16 mg to 32 mg) 
during the first 12 weeks followed by monthly injections (64 mg to 160 mg) during the last 12 weeks, 
plus daily doses of sublingual placebo tablets during the complete treatment period. Patients in the 
sublingual buprenorphine/naloxone group (n = 215) received weekly placebo injections during the first 
12 weeks and monthly placebo injections during the last 12 weeks, plus daily sublingual 
buprenorphine/naloxone tablets during the complete treatment period (8 mg to 24 mg during the first 
12 weeks and 8 mg to 32 mg during the last 12 weeks). During the 12 weeks with monthly injections, 
patients in both groups could receive one additional 8 mg weekly Buvidal dose per month, if needed. 
Patients attended 12 weekly visits during the first 12 weeks and 6 visits during the last 12 weeks 
(3 scheduled monthly visits and 3 random urine toxicology visits). At each visit, efficacy and safety 
outcome measures were assessed.  
Of the 428 randomised patients, 69.0% (147/213) of the patients in the Buvidal treatment group and 
72.6% (156/215) of the patients in the sublingual buprenorphine/naloxone treatment group completed 
the 24-week treatment period.  
The study met the primary endpoint of non-inferiority in mean percentage of urine samples negative 
for illicit opioids during treatment weeks 1 to 24 for the Buvidal group compared with the sublingual 
buprenorphine/naloxone group (Table 4).  
Superiority of Buvidal versus sublingual buprenorphine/naloxone was met (pre-specified test order) 
for the secondary endpoint cumulative distribution function (CDF) for percentage of opioid-negative 
urine samples during treatment weeks 4 to 24 (Table 4).  
 
Table 4. Efficacy variables in a pivotal phase 3, randomised, double-blind, double-

dummy, active-controlled, flexible-dose study in patients with moderate to 
severe opioid dependence 

Efficacy variable Statistic Buvidal SL BPN/NX 
Treatment 
difference (%)a 
(95% CI) 

P-value 

Percentage of urine 
samples negative for illicit 
opioids 

N 213 215   
LS mean 
(%) (SE)  35.1 (2.48) 28.4 (2.47) 6.7 <0.001 

95% CI 30.3 - 40.0 23.5 - 33.3 -0.1 - 13.6  

CDF of percentage of urine 
samples negative for illicit 
opioids over weeks 4-24 

N 213 215   

Median 26.7 6.7 - 0.008b 

CDF = cumulative distribution function, CI = confidence interval, LS = least squares; SE = standard 
error, SL BPN/NX = sublingual buprenorphine/naloxone 
a Difference = Buvidal – SL BPN/NX. 
b The p-value was for superiority  
 
A long-term, open-label, phase 3 safety study with flexible dosing of weekly and monthly Buvidal for 
48 weeks was conducted. The study enrolled a total of 227 patients with moderate to severe opioid 
dependence, of which 190 patients were switched from sublingual buprenorphine (with or without 
naloxone), and 37 patients were new to buprenorphine treatment. During the 48-week treatment 



31 

period, patients could be transitioned between weekly and monthly injections with Buvidal and 
between doses (8 mg to 32 mg weekly Buvidal and 64 mg to 160 mg monthly Buvidal) according to 
the physician’s clinical judgement.  
For patients who were switched from sublingual buprenorphine, the percentage of patients with illicit 
opioid-negative urine samples was 78.8% at baseline and 84.0% at the end of the 48-week treatment 
period. For the new-to-treatment patients, the percentage of patients with illicit opioid-negative urine 
samples was 0.0% at baseline and 63.0% at the end of the 48-week treatment period. Overall, 
156 patients (68.7%) completed the 48-week treatment period. 
 
5.2 Pharmacokinetic properties 
 
Monthly Buvidal 
 
Absorption 
 
After injection, the buprenorphine plasma concentration increases with a median time to maximum 
plasma concentration (tmax) of 6-10 hours. Buvidal has complete absolute bioavailability. Steady-state 
exposure is reached at the fourth monthly dose.  
 
Dose-proportional increases in exposure are observed in the dose interval 64 mg to 128 mg. 
 
Distribution 
 
The apparent volume of distribution for buprenorphine is approximately 1900 L. Buprenorphine is 
approximately 96% protein-bound, primarily to alpha and beta globulin.  
 
Biotransformation and elimination 
 
Buprenorphine is oxidatively metabolised by 14-N-dealkylation to N-desalkyl-buprenorphine (also 
known as norbuprenorphine) via cytochrome P450 CYP3A4 and by glucuroconjungation of the parent 
molecule and the dealkylated metabolite. Norbuprenorphine is a µ-opioid agonist with weak intrinsic 
activity.  
 
Subcutaneous administration of Buvidal results in significantly lower plasma concentrations of 
norbuprenorphine metabolite compared to administration of sublingual buprenorphine, due to 
avoidance of first-pass metabolism. 
 
Elimination of buprenorphine from Buvidal is release-rate limited with a terminal half-life ranging 
from 19 to 25 days.  
 
Buprenorphine is primarily eliminated in the faeces by biliary excretion of the glucuroconjugated 
metabolites (70%), the remainder being eliminated in the urine. Total clearance of buprenorphine is 
approximately 68 L/h. 
 
Special populations 
 
Elderly 
No pharmacokinetic data in elderly patients (> 65 years) are available. 
 
Renal impairment 
Renal elimination plays a relatively small role (≈ 30%) in the overall clearance of buprenorphine. No 
dose modification based on renal function is required, but caution is recommended when dosing 
subjects with severe renal impairment (see sections 4.2 and 4.4). 
 



32 

Hepatic impairment 
Table 5 summarises the results of a clinical study in which exposure to buprenorphine was determined 
following administration of a buprenorphine/naloxone 2.0/0.5 mg sublingual tablet in healthy subjects 
and in subjects with different degrees of hepatic impairment. 
 

Table 5.  Effect of hepatic impairment (change relative to healthy subjects) on 
pharmacokinetic parameters of buprenorphine following sublingual 
buprenorphine/naloxone administration (2.0/0.5 mg) in healthy subjects, and in 
subjects with varied degrees of hepatic impairment 

Pharmacokinetic 
Parameter 

mild hepatic 
impairment 
(Child-Pugh Class A) 
(n=9) 

moderate hepatic 
impairment 
(Child-Pugh Class B) 
(n=8) 

severe hepatic 
impairment 
(Child-Pugh Class C) 
(n=8) 

Buprenorphine 
Cmax 1.2-fold increase  1.1-fold increase  1.7-fold increase  
AUClast Similar to control  1.6-fold increase  2.8-fold increase  

 
Overall, buprenorphine plasma exposure increased approximately 3-fold in subjects with severely 
impaired hepatic function (see sections 4.2, 4.3 and 4.4). 
 
Paediatric population 
No pharmacokinetic data in paediatrics (less than 18 years) are available. Simulated buprenorphine 
exposure data in adolescents aged 16 years show lower Cmax and AUC compared to observed values in 
adults for weekly and monthly Buvidal. 
 
5.3 Preclinical safety data 
 
Acute toxicity of buprenorphine was determined in mice and rats following oral and parenteral 
(intravenous, intraperitoneal) administration. Undesirable effects were based on the known 
pharmacological activity of buprenorphine. 
 
Buprenorphine showed low tissue and biochemical toxicities when beagles were dosed subcutaneously 
for one month, rhesus monkeys orally for one month and rats and baboons intramuscularly for six 
months. 
 
Teratology and reproduction toxicity studies in rats and rabbits by intramuscular administration 
concluded that buprenorphine is not embryotoxic or teratogenic and has no marked effects on weaning 
potential. In rats there were no adverse effects on fertility of general reproductive function. 
Chronic toxicity studies in rat and dog of the vehicle used for Buvidal revealed no special hazard for 
humans. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
Buvidal 64 mg, 96 mg, 128 mg 
 
Soybean phosphatidylcholine 
Glycerol dioleate 
N-Methylpyrrolidone 
 
6.2 Incompatibilities 
 
This medicinal product must not be mixed with other medicinal products.  
 



33 

6.3 Shelf life 
 
3 years 
 
6.4 Special precautions for storage 
 
Do not refrigerate or freeze. 
 
6.5 Nature and contents of container  
 
A 1 mL pre-filled syringe (glass, Type I) with plunger stopper (fluoropolymer-coated bromobutyl 
rubber) with needle (½-inch, 23 gauge, 12 mm) and needle shield (styrene butadiene rubber). The pre-
filled syringe is assembled in a safety device for post-injection needlestick prevention. The needle 
shield of the safety syringe may contain rubber latex that may cause allergic reactions in latex-
sensitive individuals. 
 
Pack sizes 
 
Pack contains 1 pre-filled syringe with stopper, needle, needle shield, safety device and 1 plunger rod. 
 
6.6 Special precautions for disposal and other handling 
 
Important information 
 
• Administration should be made into the subcutaneous tissue 
• Intravascular, intramuscular and intradermal administration must be avoided. 
• Must not be used if the safety syringe is broken or the packaging is damaged. 
• The needle shield of the syringe may contain rubber latex that may cause allergic reactions in 

latex sensitive individuals. 
• Handle the safety syringe carefully to avoid a needle stick. The safety syringe includes a needle 

protection safety device that will activate at the end of the injection. Do not uncap the safety 
syringe until you are ready to inject. Once uncapped, never try to recap the needle. 

• Dispose of the used safety syringe right away after use. Do not re-use the safety syringe. 
 
Before administration 
 
Safety syringe parts: 

 
Figure 1: Safety Syringe: Before Use 

a) Needle shield, b) Syringe Guard Body, 
c) Syringe Guard Wings, d) Plunger,  
e) Plunger Head 

Safety Syringe: After Use 
(With needle protection mechanism activated) 

 
Please note that the smallest injection volume is barely visible in the viewing window as the 
spring of the safety device is “covering” part of the glass cylinder close to the needle. 

 



34 

Administration (see also section 4.2) 
 
- Take the syringe out of the cardboard box: pick up the syringe by the syringe guard body. 
- While holding the syringe by the needle shield, insert the plunger rod into the plunger stopper 

by gently rotating the plunger rod clockwise until secured (see Figure 2). 
 

 
Figure 2: Before After 

 
- Inspect the safety syringe closely: 

- Do not use the safety syringe after the expiration date shown on the cardboard box or on 
the syringe label. 

- A small air bubble may be seen, which is normal. 
- The liquid should be clear. Do not use the safety syringe if the liquid contains visible 

particles or is cloudy. 
 
- Choose the injection site. Injections should be rotated between sites in the buttock, thigh, 

abdomen, or upper arm (see Figure 3) with a minimum of 8 weeks before re-injecting a 
previously used injection site. Injections on the waistline or within 5 cm of the navel should be 
avoided. 

 

 
Figure 3: 
 
- Put on gloves and clean the injection site with a circular motion using an alcohol wipe (not 

provided in the pack). Do not touch the cleaned area again before injecting. 
- While holding the safety syringe by the syringe guard body as shown (see Figure 4), carefully 

pull the needle shield straight off. Immediately dispose of the needle shield (never try to recap 
the needle). A drop of liquid may be seen at the end of the needle. This is normal. 



35 

 

 
Figure 4:  
 
- Pinch the skin at the injection site between the thumb and finger as shown (see Figure 5). 
- Hold the safety syringe as shown and smoothly insert the needle at an angle of approximately 

90° (see Figure 5). Push the needle all the way in. 

 
Figure 5:  
 
- While holding the syringe as shown (see Figure 6), slowly depress the plunger until the plunger 

head latches between the syringe guard wings and all the solution is injected.  
 

 
Figure 6:  
 
- Gently pull the needle out of the skin. It is recommended that the plunger is kept fully depressed 

while the needle is carefully lifted straight out from the injection site (see Figure 7). 



36 

 

 
Figure 7:  
 
- As soon as the needle has been completely removed from the skin, slowly take the thumb off 

the plunger and allow the syringe guard to automatically cover the exposed needle (see 
Figure 8). There may be a small amount of blood at the injection site, if required wipe with a 
cotton ball or gauze.  

 
Figure 8: 
 
Disposing of the syringe 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
Phone: +800 2577 2577 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Buvidal prolonged-release solution for injection (monthly)  
EU/1/18/1336/005 [64 mg buprenorphine/0.18 mL] 
EU/1/18/1336/006 [96 mg buprenorphine/0.27 mL] 
EU/1/18/1336/007 [128 mg buprenorphine/0.36 mL] 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation:  



37 

20 November 2018 
 
 
10. DATE OF REVISION OF THE TEXT 
 
 
Detailed information on this medicinal product is available on the website of the European Medicines 
Agency http://www.ema.europa.eu 
 
  



38 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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 

 



39 

A. MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 
 
Name and address of the manufacturer(s) responsible for batch release 
Rechon Life Science AB 
Soldattorpsvägen 5 
Limhamn 
21613 
Sweden 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to special and 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.  

  



40 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 
  



41 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 
  



42 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 8 mg prolonged-release solution for injection buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 8 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
Once weekly 
For single use only 
 
 
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 
 
Do not refrigerate or freeze 
 
 



43 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/001  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
 
  



44 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 8 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
8 mg / 0.16 ml 
 
 
6. OTHER 
 
 
  



45 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 16 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 16 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once weekly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



46 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/002  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN:  
 
  



47 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 16 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
16 mg / 0.32 ml 
 
 
6. OTHER 
 
 
  



48 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 24 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 24 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once weekly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



49 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/003  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



50 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 24 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
24 mg / 0.48 ml 
 
 
6. OTHER 
 
 



51 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 32 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 32 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous  
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once weekly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



52 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/004  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



53 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 32 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
32 mg / 0.64 ml 
 
 
6. OTHER 
 
 
  



54 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 64 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 64 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, N-methylpyrrolidone 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once monthly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



55 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/005  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
 
  



56 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 64 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
64 mg / 0.18 ml 
 
 
6. OTHER 
 
 



57 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 96 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 96 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, N-methylpyrrolidone 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once monthly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



58 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/006  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN:  
NN: 
 
  



59 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 96 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
96 mg / 0.27 ml 
 
 
6. OTHER 
 
 



60 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON 
Pre-filled syringe 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
Buvidal 128 mg prolonged-release solution for injection 
buprenorphine 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 128 mg buprenorphine  
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: Soybean phosphatidylcholine, glycerol dioleate, N-methylpyrrolidone 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Prolonged-release solution for injection  
1 pre-filled syringe with safety device and 1 plunger rod 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use 
Subcutaneous use 
For single use only 
Once monthly 
 
 
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 
 
Do not refrigerate or freeze 
 
 



61 

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 
 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/18/1336/007  
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
Justification for not including Braille accepted. 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC: 
SN: 
NN: 
  



62 

MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE  
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
Buvidal 128 mg prolonged-release solution for injection 
buprenorphine 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
128 mg / 0.36 ml 
 
 
6. OTHER 
 
 
  



63 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 

B. PACKAGE LEAFLET 



64 

Package leaflet: Information for the user 
 

Buvidal 8 mg prolonged-release solution for injection 
Buvidal 16 mg prolonged-release solution for injection 
Buvidal 24 mg prolonged-release solution for injection 
Buvidal 32 mg prolonged-release solution for injection 
Buvidal 64 mg prolonged-release solution for injection 
Buvidal 96 mg prolonged-release solution for injection 

Buvidal 128 mg prolonged-release solution for injection 
 

buprenorphine 
 
Read all of this leaflet carefully before you start receiving 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. 
- 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 Buvidal is and what it is used for  
2. What you need to know before you use Buvidal 
3. How Buvidal is given 
4. Possible side effects  
5. How to store Buvidal 
6. Contents of the pack and other information 
 
 
1. What Buvidal is and what it is used for 
 
Buvidal contains the active substance buprenorphine, which is a type of opioid medicine. It is used to 
treat opioid dependence in patients who are also receiving medical, social and psychological support. 
Buvidal is intended for use in adults and adolescents aged 16 years or over. 
 
 
2. What you need to know before you receive Buvidal 
 
You must not receive Buvidal: 
 
- if you are allergic to buprenorphine or any of the other ingredients of this medicine (listed in 

section 6). 
- if you have serious breathing problems 
- if you have serious liver problems 
- if you are intoxicated with alcohol or have trembling, sweating, anxiety, confusion or 

hallucinations caused by alcohol 
 
Warnings and precautions 
 
Talk to your doctor before receiving Buvidal if you have: 
- asthma or other breathing problems 
- any liver disease such as hepatitis 
- severe kidney impairment 
- certain heart rhythm conditions (long QT syndrome or prolonged QT interval) 
- low blood pressure 
- recently suffered a head injury or brain disease 



65 

- a urinary disorder (especially linked to enlarged prostate in men) 
- thyroid problems 
- an adrenocortical disorder (e.g. Addison’s disease) 
- gall bladder problems 
 
Important things to be aware of 
- Breathing problems: Some people have died from very slow or shallow breathing caused by 

taking buprenorphine with other central nervous system depressants (substances that slow down 
some brain activity) such as benzodiazepines, alcohol or other opioids.  

- Drowsiness: This medicine may cause drowsiness especially when used with alcohol or other 
central nervous system depressants (substances that slow down some brain activity) such as 
benzodiazepines, other medicines that reduce anxiety or cause sleepiness, pregabalin or 
gabapentin. 

- Dependence: This medicine can cause dependence. 
- Liver damage: Liver damage can occur with buprenorphine, especially when it is misused. It 

can also occur because of viral infections (chronic hepatitis C), alcohol abuse, anorexia (eating 
disorder) or use of other medicines which harm your liver. Your doctor may ask you to have 
regular blood tests to check your liver. Tell your doctor if you have any liver problems before 
you start treatment with Buvidal. 

- Withdrawal symptoms: This medicine can cause withdrawal symptoms if you take it less than 
6 hours after you use a short-acting opioid (e.g. morphine, heroin) or less than 24 hours after 
you use a long-acting opioid such as methadone. 

- Blood pressure: This medicine may cause your blood pressure to drop suddenly, causing you to 
feel dizzy if you get up too quickly from sitting or lying down. 

- Diagnosis of unrelated medical conditions: This medicine may mask pain and make it 
difficult to diagnose some diseases. Do not forget to tell your doctor that you are being treated 
with this medicine. 

 
Children and adolescents 
 
Buvidal is not for use in children below 16 years of age. You will be more closely monitored by your 
doctor if you are an adolescent (16-17 years old). 
 
Other medicines and Buvidal 
 
Tell your doctor if you are taking, have recently taken or might take any other medicines. 
Some medicines may increase the side effects of Buvidal and may cause very serious reactions.  
 
It is especially important to tell your doctor if you are taking: 
- benzodiazepines (used to treat anxiety or sleep disorders). Taking too much of a 

benzodiazepine together with Buvidal may lead to death because both medicines can cause very 
slow and shallow breathing (respiratory depression). If you need a benzodiazepine, your doctor 
will prescribe the correct dose. 

- gabapentinoids (gabapentin or pregabalin) (used to treat epilepsy or neuropathic pain). 
Taking too much of a gabapentinoid may lead to death because both medicines can cause very 
slow and shallow breathing (respiratory depression). You must use the dose that your doctor has 
prescribed for you. 

- alcohol or medicines containing alcohol. Alcohol can worsen the sedative effect of this 
medicine. 

- other medicines that may make you feel sleepy which are used to treat illnesses such as 
anxiety, sleeplessness, convulsions (fits) and pain. These medicines when taken together with 
Buvidal can slow down some brain activity and reduce alertness and how well you will drive 
and use machines. 
Examples of medicines that can make you feel sleepy or less alert include: 
• other opioids such as methadone, certain painkillers and cough medicines. These 

medicines may also increase the risk of opioid overdose 
• antidepressants (used to treat depression) 



66 

• sedative antihistamines (used to treat allergic reactions) 
• barbiturates (used to cause sleep or sedation) 
• certain anxiolytics (used to treat anxiety disorders) 
• antipsychotics (used to treat psychiatric disorders such as schizophrenia) 
• clonidine (used to treat high blood pressure) 

- opioid painkillers. These medicines may not work properly when taken together with Buvidal 
and they may increase the risk of overdose. 

- naltrexone and nalmefene (used to treat addiction disorders) as they can stop Buvidal from 
working properly. You should not take them at the same time as this medicine. 

- certain antiretrovirals (used to treat HIV infection) such as ritonavir, nelfinavir or indinavir as 
they may increase the effects of this medicine. 

- certain antifungal medicines (used to treat fungal infections) such as ketoconazole, 
itraconazole as they may increase the effects of this medicine. 

- macrolide antibiotics (used to treat bacterial infections) such as clarithromycin and 
erythromycin as they may increase the effects of this medicine. 

- certain antiepileptic medicines (used to treat epilepsy) such as phenobarbital, carbamazepine 
and phenytoin as they may decrease the effect of Buvidal. 

- rifampicin (used to treat tuberculosis). Rifampicin may decrease the effect of Buvidal. 
- monoamine oxidase inhibitors (used to treat depression) such as phenelzine, isocarboxazid, 

iponiazid and tranylcypromine as they may increase the effects of this medicine. 
 
Buvidal with alcohol 
 
Taking alcohol with this medicine may increase drowsiness and may increase the risk of breathing 
problems. 
 
Pregnancy and breast-feeding 
 
If you are pregnant or breast-feeding, think you may become pregnant or are planning to have a baby, 
ask your doctor for advice before you are given this medicine. The risks of using Buvidal in pregnant 
women are not known. Your doctor will help you decide if you should continue taking the medicine 
during pregnancy. 
Using this medicine during late pregnancy may cause drug withdrawal symptoms including breathing 
problems in your new-born baby. This may happen from several hours to several days after birth. 
 
Check with your doctor before using Buvidal during breastfeeding as this medicine passes into breast 
milk. 
 
Driving and using machines 
 
Buvidal may make you sleepy and dizzy. This is more likely at the start of treatment and when your 
dose is being changed. These effects can be worse if you drink alcohol or take other sedative 
medicines. Do not drive, use any tools or machines, or perform dangerous activities until you know 
how this medicine affects you. 
 
Buvidal contains alcohol 
 
Buvidal 8 mg, 16 mg, 24 mg and 32 mg contain small amounts of ethanol (alcohol), less than 100 mg 
per dose. 
 
 
3. How to use Buvidal 
 
Buvidal must be given by healthcare professionals only.  
 
Buvidal 8 mg, 16 mg, 24 mg and 32 mg are given weekly. Buvidal 64 mg, 96 mg and 128 mg are 
given monthly. 



67 

 
Your doctor will determine the best dose for you. During your treatment, the doctor may adjust the 
dose, depending on how well the medicine works. 
 
Starting treatment 
The first dose of Buvidal will be given to you when you show clear signs of withdrawal.  
If you are dependent on short-acting opioids (e.g. morphine or heroin), the first dose of Buvidal will be 
given to you at least 6 hours after you last used an opioid. 
If you are dependent on long-acting opioids (e.g. methadone), your dose of methadone will be reduced 
to below 30 mg per day before beginning with Buvidal. The first dose of this medicine will be given to 
you at least 24 hours after you last used methadone. 
 
If you are not already receiving sublingual (under the tongue) buprenorphine (the same active 
substance as in Buvidal), the recommended starting dose is 16 mg, with one or two additional Buvidal 
8 mg doses given at least 1 day apart during the first treatment week. This means a target dose of 
24 mg or 32 mg during the first treatment week. 
If you have not used buprenorphine before you will receive a 4 mg sublingual buprenorphine dose and 
be observed for an hour before the first Buvidal dose. 
 
Buvidal for monthly treatment can be used, if appropriate for you, once stabilisation has been achieved 
with Buvidal for weekly treatment (four weeks treatment or more, where practical).  
 
If you are already taking sublingual buprenorphine, you can start receiving Buvidal the day after your 
last treatment. Your doctor will prescribe the correct starting dose of Buvidal for you depending on the 
dose of sublingual buprenorphine you are now taking. 
 
Continuing treatment and dose adjustment 
During continued treatment with Buvidal, your doctor may decrease or increase your dose according 
to your need. You may be switched from weekly and monthly treatment and from monthly to weekly 
treatment. Your doctor will prescribe the correct dose for you. 
During continued treatment, you might receive one additional Buvidal 8 mg dose between your 
weekly or monthly treatments if your doctor thinks this is appropriate for you. 
The maximum dose per week if you are on weekly Buvidal treatment is 32 mg with an additional 8 mg 
dose. The maximum dose per month if you are on monthly Buvidal treatment is 128 mg with an 
additional 8 mg dose.  
 
Route of administration 
Buvidal is given as a single injection under the skin (subcutaneously) in any of the allowed injection 
areas buttock, thigh, abdomen or upper arm. You can receive several injections in the same injection 
area, but the exact injection sites will be different for each weekly and monthly injection for a 
minimum period of 8 weeks. 
 
If you use more buprenorphine than you should 
 
If you have received more buprenorphine than you should you need to contact your doctor 
immediately since this can cause very slow and shallow breathing which can lead to death.  
 
If you use too much buprenorphine, you must immediately seek medical attention as overdose may 
cause serious and life-threatening breathing problems. Symptoms of overdose may include breathing 
more slowly and weakly than usual, feeling more sleepy than normal, smaller pupils. If you start to 
feel faint as this may be a sign of low blood pressure, feeling sick, vomit and/or slurred speech. 
 
If you miss a dose of Buvidal 
 
It is very important to keep all your appointments to receive Buvidal. If you miss an appointment, ask 
your doctor when to schedule your next dose. 
 



68 

If you stop using Buvidal 
 
Do not stop treatment without checking with the doctor who is treating you. Stopping treatment may 
cause withdrawal symptoms. 
If you have any further questions on the use of this product, ask your doctor. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
Tell your doctor immediately or get urgent medical attention if you have side effects such as: 
- sudden wheezing, difficulty breathing, swelling of the eyelids, face, tongue, lips, throat or 

hands; rash or itching especially over your whole body. These may be signs of a life-threatening 
allergic reaction. 

- if you start to breathe more slowly or weakly than usual (respiratory depression). 
- if you start to feel faint, as this may be a sign of low blood pressure. 
 
Also tell your doctor immediately if you get side effects such as: 
- severe tiredness, have no appetite or if your skin or eyes look yellow. These may be symptoms 

of liver damage. 
 
Other side effects: 
Very common side effects (may affect more than 1 in 10 people): 
- Insomnia (inability to sleep) 
- Headache 
- Nausea (feeling sick) 
- Sweating, drug withdrawal syndrome, pain 
 
Common side effects (may affect up to 1 in 10 people): 
- Infection, influenza, sore throat and painful swallowing, runny nose 
- Swollen glands (lymph nodes) 
- Hypersensitivity 
- Decreased appetite 
- Anxiety, agitation, depression, hostility, nervousness, abnormal thinking, paranoia 
- Sleepiness, feeling dizzy, migraine, burning or tingling in hands and feet, fainting, tremor, 

increase in muscle tension, speech disorders 
- Watery eyes, abnormal widening or narrowing of the pupil (the dark part of the eye) 
- Palpitations 
- Low blood pressure 
- Cough, shortness of breath, yawning, asthma, bronchitis 
- Constipation, vomiting (being sick), belly pain, flatulence (wind), indigestion, dry mouth, 

diarrhoea 
- Rash, itching, hives 
- Joint pain, back pain, muscle pain, muscle spasms, neck pain, bone pain 
- Painful period 
- Injection site reactions e.g. pain, itching, red skin, swelling and hardening of skin, swelling of 

the ankles, feet or fingers, weakness, feeling unwell, fever, chills, drug withdrawal syndrome in 
the new-born, chest pain 

- Abnormal liver test results 
 
Uncommon side effects (may affect up to 1 in 100 people): 
- Skin infection at the injection site 
- A feeling of dizziness or spinning (vertigo) 
 
Not known (frequency cannot be estimated from the available data): 
- Hallucinations, feeling happiness and excitement (euphoria) 



69 

- Abnormal redness of the skin 
- Painful or difficult urination 
 
Reporting of side effects 
 
If you get any side effects, talk to your doctor. 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 Buvidal 
 
Buvidal is for administration of healthcare professionals only. Take-home use or self-administration of 
the product by patients is not allowed. 
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 carton or the syringe label after 
EXP. The expiry date refers to the last day of that month. 
Do not refrigerate or freeze. 
Do not use this medicine if you notice visible particles or if it is cloudy. 
Buvidal is for single use only. Any used syringe should be discarded. 
 
 
6. Contents of the pack and other information 
 
What Buvidal contains  
- The active substance is buprenorphine 
- The other ingredients are soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous 

(only in weekly formulation) and N-methylpyrrolidone (only in monthly formulation). 
 
The following syringes are available: 
 
Weekly injection: 
8 mg: Pre-filled syringe containing 8 mg buprenorphine in 0.16 mL solution 
16 mg: Pre-filled syringe containing 16 mg buprenorphine in 0.32 mL solution 
24 mg: Pre-filled syringe containing 24 mg buprenorphine in 0.48 mL solution 
32 mg: Pre-filled syringe containing 32 mg buprenorphine in 0.64 mL solution 
 
Monthly injection: 
64 mg: Pre-filled syringe containing 64 mg buprenorphine in 0.18 ml solution 
96 mg: Pre-filled syringe containing 96 mg buprenorphine in 0.27 ml solution 
128 mg: Pre-filled syringe containing 128 mg buprenorphine in 0.36 ml solution 
 
What Buvidal looks like and contents of the pack 
 
Buvidal is a prolonged-release solution for injection. Each pre-filled syringe contains a yellowish to 
yellow clear liquid.  
 
The following pack sizes are available:  
Pre-filled syringes containing 8 mg, 16 mg, 24 mg, 32 mg, 64 mg, 96 mg and 128 mg solution for 
injection. 
Each pack contains 1 pre-filled syringe with stopper, needle, needle shield, safety device and 1 plunger 
rod. 
 



70 

Marketing Authorisation Holder 
Camurus AB 
Ideon Science Park 
SE-223 70 Lund, Sweden 
Tel: +800 2577 2577 
 
Manufacturer 
Rechon Life Science AB 
Soldattorpsvägen 5 
216 13 Limhamn 
Sweden 
 
 
This leaflet was last revised in {MM/YYYY}. 
 
Detailed information on this medicine is available on the European Medicines Agency web site: 
http://www.ema.europa.eu.  
 
 
------------------------------------------------------------------------------------------------------------------------ 
 
The following information is intended for healthcare professionals only: 
 

Instructions for Use for Healthcare Professionals 
 
Contents: 
 
1. Important information 
2. Before administration 
3. Administration 
4. Disposing of the syringe 
 
 
1. Important information 
 
- Injection should be made into the subcutaneous tissue. Do not use if the safety syringe is broken 

or the packaging is damaged. 
- The needle shields of the safety syringe may contain rubber latex that may cause allergic 

reactions in latex-sensitive individuals. 
- Handle the safety syringe carefully to avoid a needle stick. The safety syringe includes a needle 

protection safety device that will activate at the end of the injection. The needle protection will 
help to prevent needle stick injuries. 

- Do not uncap the safety syringe until you are ready to inject. Once uncapped never try to recap 
the needle. 

- Dispose of the used safety syringe right away after use. Do not reuse the safety syringe. 
 
 



71 

2. Before administration 
 
Safety syringe parts 

 
Figure 1: Safety Syringe: Before Use 

a) Needle shield 
b) Syringe Guard Body 
c) Syringe Guard Wings 
d) Plunger,  
e) Plunger Head 

Safety Syringe: After Use 
(With needle protection mechanism 
activated) 

Please note that the smallest injection volume is barely visible in the viewing window as the 
spring of the safety device “cover” part of the glass cylinder close to the needle. 

 
 
3. Administration 
 
- Take the syringe out of the cardboard box: pick up the syringe by the syringe guard body. 
- While holding the syringe by the needle shield, insert the plunger rod into the plunger stopper 

by gently rotating the plunger rod clockwise until secured (see Figure 2) 
 

 
Figure 2 Before After 

 
- Inspect the safety syringe closely: 

• Do not use the safety syringe after the expiration date shown on the cardboard box or on 
the syringe label. 

• A small air bubble may be seen, which is normal. 
• The liquid should be clear. Do not use the safety syringe if the liquid contains particles or 

is cloudy. 
- Choose the injection site. Injections should be rotated between sites in the buttock, thigh, 

abdomen, or upper arm (see Figure 3) with a minimum of 8 weeks before re-injecting a 
previously used injection site. Injections on the waistline or within 5 cm of the navel should be 
avoided. 

 



72 

 
Figure 3 
 
- Put on gloves and clean the injection site with a circular motion using an alcohol wipe (not 

provided in the pack). Do not touch the cleaned area again before injecting. 
- While holding the safety syringe by the syringe guard body as shown (see Figure 4), carefully 

pull the needle shield straight off. Immediately dispose of the needle shield (never try to recap 
the needle). A drop of liquid may be seen at the end of the needle. This is normal. 

 

 
Figure 4 
 
- Pinch the skin at the injection site between the thumb and finger as shown (see Figure 5). 
- Hold the safety syringe as shown and smoothly insert the needle at an angle of 

approximately 90° (see Figure 5). Push the needle all the way in. 
 

 
Figure 5 
 
- While holding the syringe as shown (see Figure 6), slowly depress the plunger until the plunger 

head latches between the syringe guard wings and all the solution is injected. 



73 

 

 
Figure 6 
 
- Gently pull the needle out of the skin. It is recommended that the plunger is kept fully depressed 

while the needle is carefully lifted straight out from the injection site (see Figure 7). 
 

 
 
Figure 7 
 
- As soon as the needle has been completely removed from the skin, slowly take the thumb off 

the plunger and allow the syringe guard to automatically cover the exposed needle (see 
Figure 8). There may be a small amount of blood at the injection site, if required wipe with a 
cotton ball or gauze. 
 

 
 
 
 
 
 
 
  
 
 
 
Figure 8 
 
 
4. Disposing of the syringe 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements. 
 


	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
{'Title': '1. what buvidal is and what it is used for', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '2. what you need to know before you use buvidal', 'Section_Content': None, 'Entity_Recognition': None}
{'Title': '3. how buvidal is given', 'Section_Content': 'buvidal must be given by healthcare professionals only. buvidal 8 mg, 16 mg, 24 mg and 32 mg are given weekly. buvidal 64 mg, 96 mg and 128 mg are given monthly. your doctor will determine the best dose for you. during your treatment, the doctor may adjust the dose, depending on how well the medicine works. starting treatment the first dose of buvidal will be given to you when you show clear signs of withdrawal. if you are dependent on short-acting opioids (e.g. morphine or heroin), the first dose of buvidal will be given to you at least 6 hours after you last used an opioid. if you are dependent on long-acting opioids (e.g. methadone), your dose of methadone will be reduced to below 30 mg per day before beginning with buvidal. the first dose of this medicine will be given to you at least 24 hours after you last used methadone. if you are not already receiving sublingual (under the tongue) buprenorphine (the same active substance as in buvidal), the recommended starting dose is 16 mg, with one or two additional buvidal 8 mg doses given at least 1 day apart during the first treatment week. this means a target dose of 24 mg or 32 mg during the first treatment week. if you have not used buprenorphine before you will receive a 4 mg sublingual buprenorphine dose and be observed for an hour before the first buvidal dose. buvidal for monthly treatment can be used, if appropriate for you, once stabilisation has been achieved with buvidal for weekly treatment (four weeks treatment or more, where practical). if you are already taking sublingual buprenorphine, you can start receiving buvidal the day after your last treatment. your doctor will prescribe the correct starting dose of buvidal for you depending on the dose of sublingual buprenorphine you are now taking. continuing treatment and dose adjustment during continued treatment with buvidal, your doctor may decrease or increase your dose according to your need. you may be switched from weekly and monthly treatment and from monthly to weekly treatment. your doctor will prescribe the correct dose for you. during continued treatment, you might receive one additional buvidal 8 mg dose between your weekly or monthly treatments if your doctor thinks this is appropriate for you. the maximum dose per week if you are on weekly buvidal treatment is 32 mg with an additional 8 mg dose. the maximum dose per month if you are on monthly buvidal treatment is 128 mg with an additional 8 mg dose. route of administration buvidal is given as a single injection under the skin (subcutaneously) in any of the allowed injection areas buttock, thigh, abdomen or upper arm. you can receive several injections in the same injection area, but the exact injection sites will be different for each weekly and monthly injection for a minimum period of 8 weeks. if you use more buprenorphine than you should if you have received more buprenorphine than you should you need to contact your doctor immediately since this can cause very slow and shallow breathing which can lead to death. if you use too much buprenorphine, you must immediately seek medical attention as overdose may cause serious and life-threatening breathing problems. symptoms of overdose may include breathing more slowly and weakly than usual, feeling more sleepy than normal, smaller pupils. if you start to feel faint as this may be a sign of low blood pressure, feeling sick, vomit and/or slurred speech. if you miss a dose of buvidal it is very important to keep all your appointments to receive buvidal. if you miss an appointment, ask your doctor when to schedule your next dose. if you stop using buvidal do not stop treatment without checking with the doctor who is treating you. stopping treatment may cause withdrawal symptoms. if you have any further questions on the use of this product, ask your doctor.', 'Entity_Recognition': [{'Text': 'buvidal', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 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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. tell your doctor immediately or get urgent medical attention if you have side effects such as: - sudden wheezing, difficulty breathing, swelling of the eyelids, face, tongue, lips, throat or hands; rash or itching especially over your whole body. these may be signs of a life-threatening allergic reaction. - if you start to breathe more slowly or weakly than usual (respiratory depression). - if you start to feel faint, as this may be a sign of low blood pressure. also tell your doctor immediately if you get side effects such as: - severe tiredness, have no appetite or if your skin or eyes look yellow. these may be symptoms of liver damage. other side effects: very common side effects (may affect more than 1 in 10 people): - insomnia (inability to sleep) - headache - nausea (feeling sick) - sweating, drug withdrawal syndrome, pain common side effects (may affect up to 1 in 10 people): - infection, influenza, sore throat and painful swallowing, runny nose - swollen glands (lymph nodes) - hypersensitivity - decreased appetite - anxiety, agitation, depression, hostility, nervousness, abnormal thinking, paranoia - sleepiness, feeling dizzy, migraine, burning or tingling in hands and feet, fainting, tremor, increase in muscle tension, speech disorders - watery eyes, abnormal widening or narrowing of the pupil (the dark part of the eye) - palpitations - low blood pressure - cough, shortness of breath, yawning, asthma, bronchitis - constipation, vomiting (being sick), belly pain, flatulence (wind), indigestion, dry mouth, diarrhoea - rash, itching, hives - joint pain, back pain, muscle pain, muscle spasms, neck pain, bone pain - painful period - injection site reactions e.g. pain, itching, red skin, swelling and hardening of skin, swelling of the ankles, feet or fingers, weakness, feeling unwell, fever, chills, drug withdrawal syndrome in the new-born, chest pain - abnormal liver test results uncommon side effects (may affect up to 1 in 100 people): - skin infection at the injection site - a feeling of dizziness or spinning (vertigo) not known (frequency cannot be estimated from the available data): - hallucinations, feeling happiness and excitement (euphoria) 69 - abnormal redness of the skin - painful or difficult urination reporting of side effects if you get any side effects, talk to your doctor. 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.', 'Entity_Recognition': [{'Text': 'buvidal', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 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'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9695213437080383}]}, {'Id': 132, 'BeginOffset': 1918, 'EndOffset': 1924, 'Score': 0.9987994432449341, 'Text': 'chills', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9821494221687317}]}, {'Id': 133, 'BeginOffset': 1926, 'EndOffset': 1950, 'Score': 0.9626837968826294, 'Text': 'drug withdrawal syndrome', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8467974066734314}]}, {'Id': 153, 'BeginOffset': 1958, 'EndOffset': 1966, 'Score': 0.4577657878398895, 'Text': 'new-born', 'Category': 'TIME_EXPRESSION', 'Type': 'TIME_TO_DX_NAME', 'Traits': [], 'Attributes': [{'Type': 'DX_NAME', 'Score': 0.7754612565040588, 'RelationshipScore': 0.6110913157463074, 'RelationshipType': 'OVERLAP', 'Id': 134, 'BeginOffset': 1968, 'EndOffset': 1978, 'Text': 'chest pain', 'Category': 'MEDICAL_CONDITION', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9046785235404968}]}]}, {'Id': 134, 'BeginOffset': 1968, 'EndOffset': 1978, 'Score': 0.7754612565040588, 'Text': 'chest pain', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9046785235404968}]}, {'Text': 'abnormal liver test', 'Type': 'PROBLEM', 'BeginOffset': 1981, 'EndOffset': 2000}, {'Text': 'uncommon side effects', 'Type': 'PROBLEM', 'BeginOffset': 2009, 'EndOffset': 2030}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 2049, 'EndOffset': 2050}, {'Text': '100', 'Type': 'NUMBER', 'BeginOffset': 2054, 'EndOffset': 2057}, {'Text': 'skin infection at the injection site', 'Type': 'PROBLEM', 'BeginOffset': 2069, 'EndOffset': 2105}, {'Id': 137, 'BeginOffset': 2121, 'EndOffset': 2130, 'Score': 0.9890973567962646, 'Text': 'dizziness', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9490346908569336}]}, {'Id': 138, 'BeginOffset': 2134, 'EndOffset': 2142, 'Score': 0.7130023241043091, 'Text': 'spinning', 'Category': 'MEDICAL_CONDITION', 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'Text': 'skin', 'Category': 'ANATOMY', 'Traits': []}]}, {'Id': 147, 'BeginOffset': 2329, 'EndOffset': 2348, 'Score': 0.8712721467018127, 'Text': 'difficult urination', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9397299289703369}]}, {'Id': 148, 'BeginOffset': 2362, 'EndOffset': 2374, 'Score': 0.8560745120048523, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8411768674850464}]}, {'Id': 149, 'BeginOffset': 2390, 'EndOffset': 2402, 'Score': 0.9204800128936768, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8215208649635315}]}, {'Id': 150, 'BeginOffset': 2452, 'EndOffset': 2464, 'Score': 0.9615616202354431, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7236286401748657}]}, {'Id': 151, 'BeginOffset': 2513, 'EndOffset': 2525, 'Score': 0.8705993890762329, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7382441759109497}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.48389512300491333, 'RelationshipScore': 0.8235695958137512, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 128, 'BeginOffset': 2579, 'EndOffset': 2587, 'Text': 'appendix', 'Category': 'ANATOMY', 'Traits': []}]}, {'Id': 128, 'BeginOffset': 2579, 'EndOffset': 2587, 'Score': 0.48389512300491333, 'Text': 'appendix', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 152, 'BeginOffset': 2604, 'EndOffset': 2616, 'Score': 0.7602296471595764, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7621976733207703}]}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 2672, 'EndOffset': 2685}]}
{'Title': '5. how to store buvidal', 'Section_Content': 'buvidal is for administration of healthcare professionals only. take-home use or self-administration of the product by patients is not allowed. 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 carton or the syringe label after exp. the expiry date refers to the last day of that month. do not refrigerate or freeze. do not use this medicine if you notice visible particles or if it is cloudy. buvidal is for single use only. any used syringe should be discarded.', 'Entity_Recognition': [{'Text': 'buvidal', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'self-administration of the product', 'Type': 'TREATMENT', 'BeginOffset': 81, 'EndOffset': 115}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 214, 'EndOffset': 227}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 407, 'EndOffset': 420}, {'Text': 'visible particles', 'Type': 'PROBLEM', 'BeginOffset': 435, 'EndOffset': 452}, {'Text': 'cloudy', 'Type': 'PROBLEM', 'BeginOffset': 465, 'EndOffset': 471}, {'Text': 'any used syringe', 'Type': 'TREATMENT', 'BeginOffset': 505, 'EndOffset': 521}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what buvidal contains - the active substance is buprenorphine - the other ingredients are soybean phosphatidylcholine, glycerol dioleate, ethanol anhydrous (only in weekly formulation) and n-methylpyrrolidone (only in monthly formulation). the following syringes are available: weekly injection: 8 mg: pre-filled syringe containing 8 mg buprenorphine in 0.16 ml solution 16 mg: pre-filled syringe containing 16 mg buprenorphine in 0.32 ml solution 24 mg: pre-filled syringe containing 24 mg buprenorphine in 0.48 ml solution 32 mg: pre-filled syringe containing 32 mg buprenorphine in 0.64 ml solution monthly injection: 64 mg: pre-filled syringe containing 64 mg buprenorphine in 0.18 ml solution 96 mg: pre-filled syringe containing 96 mg buprenorphine in 0.27 ml solution 128 mg: pre-filled syringe containing 128 mg buprenorphine in 0.36 ml solution what buvidal looks like and contents of the pack buvidal is a prolonged-release solution for injection. each pre-filled syringe contains a yellowish to yellow clear liquid. the following pack sizes are available: pre-filled syringes containing 8 mg, 16 mg, 24 mg, 32 mg, 64 mg, 96 mg and 128 mg solution for injection. each pack contains 1 pre-filled syringe with stopper, needle, needle shield, safety device and 1 plunger rod.', 'Entity_Recognition': [{'Text': 'buvidal', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 0, 'BeginOffset': 48, 'EndOffset': 61, 'Score': 0.9689638614654541, 'Text': 'buprenorphine', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 1, 'BeginOffset': 90, 'EndOffset': 117, 'Score': 0.8016781806945801, 'Text': 'soybean phosphatidylcholine', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 2, 'BeginOffset': 119, 'EndOffset': 136, 'Score': 0.9049994945526123, 'Text': 'glycerol dioleate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 3, 'BeginOffset': 138, 'EndOffset': 155, 'Score': 0.6054754257202148, 'Text': 'ethanol anhydrous', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 4, 'BeginOffset': 189, 'EndOffset': 208, 'Score': 0.9939373731613159, 'Text': 'n-methylpyrrolidone', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'DOSAGE', 'Score': 0.8838648796081543, 'RelationshipScore': 0.9819929599761963, 'RelationshipType': 'DOSAGE', 'Id': 5, 'BeginOffset': 296, 'EndOffset': 300, 'Text': '8 mg', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'FORM', 'Score': 0.7168196439743042, 'RelationshipScore': 0.9982773065567017, 'RelationshipType': 'FORM', 'Id': 6, 'BeginOffset': 302, 'EndOffset': 320, 'Text': 'pre-filled syringe', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.5153231024742126, 'RelationshipScore': 0.8686987161636353, 'RelationshipType': 'DOSAGE', 'Id': 9, 'BeginOffset': 354, 'EndOffset': 361, 'Text': '0.16 ml', 'Category': 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