Ajovy
1 
 

  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX I 
 

SUMMARY OF PRODUCT CHARACTERISTICS 
 
 
  



2 
 

This medicinal product is subject to additional monitoring. This will allow quick identification of 
new safety information. Healthcare professionals are asked to report any suspected adverse reactions. 
See section 4.8 for how to report adverse reactions. 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
AJOVY 225 mg solution for injection in pre-filled syringe 
AJOVY 225 mg solution for injection in pre-filled pen 
 
 
2. QUALITATIVE AND QUANTITATIVE COMPOSITION 
 
One pre-filled syringe contains 225 mg fremanezumab. 
One pre-filled pen contains 225 mg fremanezumab. 
 
Fremanezumab is a humanised monoclonal antibody produced in Chinese Hamster Ovary (CHO) cells 
by recombinant DNA technology. 
 
For the full list of excipients, see section 6.1. 
 
 
3. PHARMACEUTICAL FORM 
 
Solution for injection (injection) 
 
Clear to opalescent, colourless to slightly yellow solution with a pH of 5.5 and an osmolality of 
300-450 mOsm/kg. 
 
 
4. CLINICAL PARTICULARS 
 
4.1 Therapeutic indications 
 
AJOVY is indicated for prophylaxis of migraine in adults who have at least 4 migraine days per 
month. 
 
4.2 Posology and method of administration 
 
The treatment should be initiated by a physician experienced in the diagnosis and treatment of 
migraine. 
 
Posology 
 
Treatment is intended for patients with at least 4 migraine days per month when initiating treatment 
with fremanezumab. 
 
Two dosing options are available: 

• 225 mg once monthly (monthly dosing) or 
• 675 mg every three months (quarterly dosing) 

 
When switching dosing regimens, the first dose of the new regimen should be administered on the 
next scheduled dosing date of the prior regimen.  
 
When initiating treatment with fremanezumab, concomitant migraine preventive treatment may be 
continued if considered necessary by the prescriber (see section 5.1). 



3 
 

 
The treatment benefit should be assessed within 3 months after initiation of treatment. Any further 
decision to continue treatment should be taken on an individual patient basis. Evaluation of the need to 
continue treatment is recommended regularly thereafter. 
 
Missed dose 
If a fremanezumab injection is missed on the planned date, dosing should resume as soon as possible 
on the indicated dose and regimen. A double dose must not be administered to make up for a missed 
dose. 
 
Special Populations 
 
Elderly 
There is limited data available on the use of fremanezumab in patients ≥65 years of age. Based on the 
results of population pharmacokinetic analysis, no dose adjustment is required (see section 5.2). 
 
Renal or hepatic impairment 
No dose adjustment is necessary in patients with mild to moderate renal impairment or hepatic 
impairment (see section 5.2). 
 
Paediatric population 
The safety and efficacy of AJOVY in children and adolescents below the age of 18 years have not yet 
been established. No data are available.  
 
Method of administration  
 
Subcutaneous use. 
 
AJOVY is for subcutaneous injection only. It should not be administered by the intravenous or 
intramuscular route. AJOVY can be injected into areas of the abdomen, thigh, or upper arm that are 
not tender, bruised, red, or indurated. For multiple injections, injection sites should be alternated. 
 
Patients may self-inject if instructed in subcutaneous self-injection technique by a healthcare 
professional. For further instructions on administration, see section 6.6. 
 
4.3 Contraindications 
 
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. 
 
4.4 Special warnings and precautions for use 
 
Traceability 
 
In order to improve the traceability of biological medicinal products, the name and the batch number 
of the administered product should be clearly recorded. 
 
Hypersensitivity 
 
Hypersensitivity reactions such as rash, pruritus, urticaria and swelling have been reported 
uncommonly with fremanezumab (see section 4.8). Most reactions were reported from within hours to 
one month after administration and were mild to moderate, but some led to discontinuation or required 
corticosteroid treatment. If a hypersensitivity reaction occurs, discontinuation of fremanezumab 
administration should be considered and appropriate therapy should be initiated. 
 



4 
 

Major cardiovascular diseases 
 
Patients with certain major cardiovascular diseases were excluded from clinical studies (see 
section 5.1). No safety data are available in these patients. 
 
Excipients 
 
This medicinal product contains less than 1 mmol sodium (23 mg) per dose, i.e., is essentially 
“sodium-free”. 
 
4.5 Interaction with other medicinal products and other forms of interaction 
 
No formal clinical drug interaction studies have been performed with AJOVY. No pharmacokinetic 
drug interactions are expected based on the characteristics of fremanezumab. Furthermore, 
concomitant use of acute migraine treatments (specifically analgesics, ergots, and triptans) and 
migraine preventive medicinal products during the clinical studies did not affect the pharmacokinetics 
of fremanezumab. 
 
4.6 Fertility, pregnancy and lactation 
 
Pregnancy 
 
There is a limited amount of data from the use of AJOVY in pregnant women. Animal studies do not 
indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a 
precautionary measure, it is preferable to avoid the use of AJOVY during pregnancy. 
 
Breast-feeding 
 
It is unknown whether fremanezumab is excreted in human milk. Human IgG is known to be excreted 
in breast milk during the first days after birth, which is decreasing to low concentrations soon 
afterwards; consequently, a risk to breast-fed infants cannot be excluded during this short period. 
Afterwards, use of fremanezumab could be considered during breast-feeding only if clinically needed. 
 
Fertility 
 
There are no fertility data in humans. Available non-clinical data do not suggest an effect on fertility 
(see section 5.3). 
 
4.7 Effects on ability to drive and use machines 
 
AJOVY has no or negligible influence on the ability to drive and use machines.  
 
4.8 Undesirable effects 
 
Summary of the safety profile 
 
A total of over 2,500 patients (more than 1,900 patient years) have been treated with AJOVY in 
registration studies. More than 1,400 patients were treated for at least 12 months. 
 
Commonly reported adverse drug reactions (ADRs) were local reactions at the injection site 
(pain [24%], induration [17%], erythema [16%] and pruritus [2%]). 
 



5 
 

Tabulated list of adverse reactions 
 
ADRs from clinical studies are presented according to MedDRA system organ classification. Within 
each frequency grouping, ADRs are presented in the order of decreasing seriousness. Frequency 
categories are based on the following convention: very common (≥1/10); common (≥1/100 to <1/10); 
uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000). Within each 
system organ class, ADRs are ranked by frequency, most frequent reactions first. 
 
The following ADRs have been identified in the AJOVY clinical development programme (Table 1).  
 
Table 1: Adverse reactions in clinical studies 

MedDRA System Organ Class Frequency Adverse Reaction 
Immune system disorders Uncommon Hypersensitivity reactions such 

as rash, pruritus, urticaria and 
swelling 

General disorders and 
administration site conditions 

Very common Injection site pain 
Injection site induration 
Injection site erythema 

Common Injection site pruritus 
Uncommon Injection site rash 

 
Description of selected adverse reactions 
 
Injection site reactions 
The most frequently observed local reactions at the injection site were pain, induration and erythema. 
All local injection site reactions were transient and predominantly mild to moderate in severity. Pain, 
induration and erythema were typically observed immediately after injection while pruritus and rash 
appeared within a median of 24 and 48 hours, respectively. All injection site reactions resolved, 
mostly within a few hours or days. Injection site reactions generally did not necessitate discontinuation 
of the medicinal product. 
 
Immunogenicity 
In placebo-controlled studies, 0.4 % of patients (6 out of 1,701) treated with fremanezumab developed 
anti-drug antibodies (ADA). The antibody responses were of low titer. One of these 6 patients 
developed neutralising antibodies. With 12 months of treatment, ADA were detected in 2.3% of the 
patients (43 out of 1,888) with 0.95% of the patients developing neutralising antibodies. The safety 
and efficacy of fremanezumab were not affected by ADA development. 
  
Reporting of suspected adverse reactions 
 
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It 
allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare 
professionals are asked to report any suspected adverse reactions via the national reporting system 
listed in Appendix V. 
 
4.9 Overdose 
 
Doses up to 2,000 mg have been administered intravenously in clinical trials without dose-limiting 
toxicity. In case of overdose, it is recommended that the patient be monitored for any signs or 
symptoms of adverse effects and given appropriate symptomatic treatment if necessary. 
 
 

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


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5. PHARMACOLOGICAL PROPERTIES 
 
5.1  Pharmacodynamic properties 
 
Pharmacotherapeutic group: Not yet assigned. ATC code: Not yet assigned. 
 
Mechanism of action 
 
Fremanezumab is a humanised IgG2Δa/kappa monoclonal antibody derived from a murine precursor. 
Fremanezumab selectively binds the calcitonin gene-related peptide (CGRP) ligand and blocks both 
CGRP isoforms (α-and β-CGRP) from binding to the CGRP receptor. While the precise mechanism of 
action by which fremanezumab prevents migraine attacks is unknown, it is believed that prevention of 
migraine is obtained by its effect modulating the trigeminal system. CGRP levels have been shown to 
increase significantly during migraine and return to normal with headache relief. 
 
Fremanezumab is highly specific for CGRP and does not bind to closely related family members (e.g., 
amylin, calcitonin, intermedin and adrenomedullin). 
 
Clinical efficacy and safety 
 
The efficacy of fremanezumab was assessed in two randomised, 12-week, double-blind, placebo-
controlled phase III studies in adult patients with episodic (Study 1) and chronic migraine (Study 2). 
The patients enrolled had at least a 12-month history of migraine (with and without aura) according to 
the International Classification of Headache Disorders (ICHD-III) diagnostic criteria. Elderly patients 
(>70 years), patients using opioids or barbiturates on more than 4 days per month, and patients with 
pre-existing myocardial infarction, cerebrovascular accident, and thromboembolic events were 
excluded. 
 
Episodic migraine study (Study 1) 
The efficacy of fremanezumab was evaluated in episodic migraine in a randomised, multicentre, 
12-week, placebo-controlled, double-blind study (Study 1). Adults with a history of episodic migraine 
(less than 15 headache days per month) were included in the study. A total of 875 patients 
(742 females, 133 males) were randomised into one of three arms: 675 mg fremanezumab every three 
months (quarterly, n=291), 225 mg fremanezumab once a month (monthly, n=290), or monthly 
administration of placebo (n=294) administered via subcutaneous injection. Demographics and 
baseline disease characteristics were balanced and comparable between the study arms. Patients had a 
median age of 42 years (range: 18 to 70 years), 85% were female, and 80% were white. The mean 
migraine frequency at baseline was approximately 9 migraine days per month. Patients were allowed 
to use acute headache treatments during the study. A sub-set of patients (21%) was also allowed to use 
one commonly used concomitant, preventive medicinal product (beta-blockers, calcium channel 
blocker/benzocycloheptene, antidepressants, anticonvulsants). Overall, 19% of the patients had 
previously used topiramate. A total of 791 patients completed the 12-week double-blind treatment 
period. 
 
The primary efficacy endpoint was the mean change from baseline in the monthly average number of 
migraine days during the 12-week treatment period. Key secondary endpoints were the achievement of 
at least 50% reduction from baseline in monthly migraine days (50% responder rate), mean change 
from baseline in the patient reported MIDAS score, and change from baseline in monthly average 
number of days of acute headache medicinal product use. Both monthly and quarterly dosing regimens 
of fremanezumab demonstrated statistically significant and clinically meaningful improvement from 
baseline compared to placebo for key endpoints (see Table 2). The effect also occurred from as early 
as the first month and sustained over the treatment period (see Figure 1). 
 



7 
 

Figure 1: Mean Change from Baseline in the Monthly Average Number of Migraine Days for 
Study 1 

<0.0001
<0.0001

<0.0001
<0.0001

0.0003
<0.0001

<0.0001
<0.0001

0.0009
<0.0001

0.0013
0.0002

AJOVY Quarterly
AJOVY Monthly

Baseline Week 1 Week 2 Week 3 Month 1 Month 2 Month 3Visit:

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

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AJOVY MonthlyAJOVY QuarterlyPlacebo

 
Mean at baseline (monthly average number of migraine days): Placebo: 9.1, AJOVY Quarterly: 9.2, AJOVY 
Monthly: 8.9. 
 
Table 2: Key Efficacy Outcomes in Study 1 in Episodic Migraine 
Efficacy Endpoint Placebo 

(n=290) 
Fremanezumab  
675 mg quarterly 
(n=288) 

Fremanezumab 
225 mg monthly 
(n=287) 

MMD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-2.2 (-2.68, -1.71) 
- 
9.1 (2.65) 

 
-3.4 (-3.94, -2.96) 
-1.2 (-1.74, -0.69) 
9.2 (2.62) 

 
-3.7 (-4.15, -3.18) 
-1.4 (-1.96, -0.90) 
8.9 (2.63) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 
MHD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-1.5 (-1.88, -1.06) 
- 
6.9 (3.13) 

 
-3.0 (-3.39, -2.55) 
-1.5 (-1.95, -1.02) 
7.2 (3.14) 

 
-2.9 (-3.34, -2.51) 
-1.5 (-1.92, -0.99) 
6.8 (2.90) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 
50% Responder Rate 
MMD 
Percentage [%] 

 
 
27.9% 

 
 
44.4% 

 
 
47.7% 

P-value (vs. placebo) - p<0.0001 p<0.0001 
75% Responder Rate 
MMD 
Percentage [%] 

 
 
9.7% 

 
 
18.4% 

 
 
18.5% 

P-value (vs. placebo) - p=0.0025 p=0.0023 
MIDAS total 
Mean changea (95% CI) 
Baseline (SD) 

 
-17.5 (-20.62, -14.47) 
37.3 (27.75) 

 
-23.0 (-26.10, -19.82) 
41.7 (33.09) 

 
-24.6 (-27.68, -21.45) 
38 (33.30) 

P-value (vs. placebo)a - p=0.0023 p<0.0001 
MAHMD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-1.6 (-2.04, -1.20) 
- 
7.7 (3.60) 

 
-2.9 (-3.34, -2.48) 
-1.3 (-1.73, -0.78) 
7.7 (3.70) 

 
-3.0 (-3.41, -2.56) 
-1.3 (-1.81, -0.86) 
7.7 (3.37) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 



8 
 

CI = confidence interval; MAHMD = monthly acute headache medication days; MHD = monthly headache days 
of at least moderate severity; MIDAS = Migraine Disability Assessment; MMD = monthly migraine days; 
SD = standard deviation; TD = treatment difference 
a For all endpoints mean change and CIs are based on the ANCOVA model that included treatment, gender, 
region, and baseline preventive medication use (yes/no) as fixed effects and corresponding baseline value and 
years since onset of migraine as covariates. 
b Treatment difference is based on the MMRM analysis with treatment, gender, region, and baseline preventive 
medication use (yes/no), month, and treatment month as fixed effects and corresponding baseline value and years 
since onset of migraine as covariates. 
 
In patients on one other concomitant, migraine preventive medicinal product, the treatment difference 
for the reduction of monthly migraine days (MMD) observed between fremanezumab 675 mg 
quarterly and placebo was -1.8 days (95% CI: -2.95, -0.55) and between fremanezumab 225 mg 
monthly and placebo -2.0 days (95% CI: -3.21, -0.86). 
 
In patients who had previously used topiramate the treatment difference for the reduction of monthly 
migraine days (MMD) observed between fremanezumab 675 mg quarterly and placebo was -2.3 days 
(95% CI: -3.64, -1.00) and between fremanezumab 225 mg monthly and placebo -2.4 days 
(95% CI: -3.61, -1.13). 
 
Chronic migraine study (Study 2) 
Fremanezumab was evaluated in chronic migraine in a randomised, multicentre, 12-week, placebo-
controlled, double-blind study (Study 2). The study population included adults with a history of 
chronic migraine (15 headache days or higher per month). A total of 1,130 patients (991 females, 
139 males) were randomised into one of three arms: 675 mg fremanezumab starting dose followed by 
225 mg fremanezumab once a month (monthly, n=379), 675 mg fremanezumab every three months 
(quarterly, n=376), or monthly administration of placebo (n=375) administered via subcutaneous 
injection. Demographics and baseline disease characteristics were balanced and comparable between 
the study arms. Patients had a median age of 41 years (range: 18 to 70 years), 88% were female, and 
79% were white. The mean headache frequency at baseline was approximately 21 headache days per 
month (of which 13 headache days were of at least moderate severity). Patients were allowed to use 
acute headache treatments during the study. A sub-set of patients (21%) was also allowed to use one 
commonly used concomitant, preventive medicinal product (beta-blockers, calcium channel 
blocker/benzocycloheptene, antidepressants, anticonvulsants). Overall, 30% of the patients had 
previously used topiramate and 15% onabotulinumtoxin A. A total of 1,034 patients completed the 
12-week double-blind treatment period. 
 
The primary efficacy endpoint was the mean change from baseline in the monthly average number of 
headache days of at least moderate severity during the 12-week treatment period. Key secondary 
endpoints were the achievement of at least 50% reduction from baseline in monthly headache days of 
at least moderate severity (50% responder rate), mean change from baseline in the patient reported 
HIT-6 score, and change from baseline in monthly average number of days of acute headache 
medicinal product use. Both monthly and quarterly dosing regimens of fremanezumab demonstrated 
statistically significant and clinically meaningful improvement from baseline compared to placebo for 
key endpoints (see Table 3). The effect also occurred from as early as the first month and sustained 
over the treatment period (see Figure 2). 
 



9 
 

Figure 2: Mean Change from Baseline in the Monthly Average Number of Headache Days of At 
Least Moderate Severity for Study 2 

<0.0001
<0.0001

<0.0001
<0.0001

<0.0001
<0.0001

<0.0001
<0.0001

<0.0001
<0.0001

0.0007
<0.0001

AJOVY Quarterly
AJOVY Monthly

Baseline Week 1 Week 2 Week 3 Month 1 Month 2 Month 3Visit:

-5.5

-5.0

-4.5

-4.0

-3.5

-3.0

-2.5

-2.0

-1.5

-1.0

-0.5

0.0

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AJOVY MonthlyAJOVY QuarterlyPlacebo

 
Mean at baseline (monthly average number of headache days of at least moderate severity): Placebo: 13.3, 
AJOVY Quarterly: 13.2, AJOVY Monthly: 12.8. 
 
Table 3: Key Efficacy Outcomes in Study 2 in Chronic Migraine 
Efficacy Endpoint Placebo 

(n=371) 
Fremanezumab  
675 mg quarterly 
(n=375) 

Fremanezumab 
225 mg monthly with 
675 mg starting dose 
(n=375) 

MHD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-2.5 (-3.06, -1.85) 
- 
13.3 (5.80) 

 
-4.3 (-4.87, -3.66) 
-1.8 (-2.45, -1.13) 
13.2 (5.45) 

 
-4.6 (-5.16, -3.97) 
-2.1 (-2.77, -1.46) 
12.8 (5.79) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 
MMD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-3.2 (-3.86, -2.47) 
- 
16.3 (5.13) 

 
-4.9 (-5.59, -4.20) 
-1.7 (-2.44, -0.92) 
16.2 (4.87) 

 
-5.0 (-5.70, -4.33) 
-1.9 (-2.61, -1.09) 
16.0 (5.20) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 
50% Responder Rate 
MHD 
Percentage [%] 

 
 
18.1% 

 
 
37.6% 

 
 
40.8% 

P-value (vs. placebo) - p<0.0001 p<0.0001 
75% Responder Rate 
MHD 
Percentage [%] 

 
 
7.0% 

 
 
14.7% 

 
 
15.2% 

P-value (vs. placebo) -  p=0.0008 p=0.0003 
HIT-6 total 
Mean changea (95% CI) 
Baseline (SD) 

 
-4.5 (-5.38, -3.60) 
64.1 (4.79) 

 
-6.4 (-7.31, -5.52) 
64.3 (4.75) 

 
-6.7 (-7.71, -5.97) 
64.6 (4.43) 

P-value (vs. placebo)a - p=0.0001 p<0.0001 
MAHMD 
Mean changea (95% CI) 
TD (95% CI)b 
Baseline (SD) 

 
-1.9 (-2.48, -1.28) 
- 
13.0 (6.89) 

 
-3.7 (-4.25, -3.06) 
-1.7 (-2.40, -1.09) 
13.1 (6.79) 

 
-4.2 (-4.79, -3.61) 
-2.3 (-2.95, -1.64) 
13.1 (7.22) 

P-value (vs. placebo)a - p<0.0001 p<0.0001 



10 
 

CI = confidence interval; HIT-6 = Headache Impact Test; MAHMD = monthly acute headache medication days; 
MHD = monthly headache days of at least moderate severity; MMD = monthly migraine days; SD = standard 
deviation; TD = treatment difference 
a For all endpoints mean change and CIs are based on the ANCOVA model that included treatment, gender, 
region, and baseline preventive medication use (yes/no) as fixed effects and corresponding baseline value and 
years since onset of migraine as covariates. 
b Treatment difference is based on the MMRM analysis with treatment, gender, region, and baseline preventive 
medication use (yes/no), month, and treatment month as fixed effects and corresponding baseline value and years 
since onset of migraine as covariates. 
 
In patients on one other concomitant, migraine preventive medicinal product, the treatment difference 
for the reduction of monthly headache days (MHD) of at least moderate severity observed between 
fremanezumab 675 mg quarterly and placebo was -1.3 days (95% CI: -2.66, 0.03) and between 
fremanezumab 225 mg monthly with 675 mg starting dose and placebo -2.0 days 
(95% CI: -3.27, -0.67). 
 
In patients who had previously used topiramate the treatment difference for the reduction of monthly 
headache days (MHD) of at least moderate severity observed between fremanezumab 675 mg 
quarterly and placebo was -2.7 days (95% CI: -3.88, -1.51) and between fremanezumab 225 mg 
monthly with 675 mg starting dose and placebo -2.9 days (95% CI: -4.10, -1.78). In patients who had 
previously used onabotulinumtoxin A the treatment difference for the reduction of monthly headache 
days (MHD) of at least moderate severity observed between fremanezumab 675 mg quarterly and 
placebo was -1.3 days (95% CI: -3.01, -0.37) and between fremanezumab 225 mg monthly with 
675 mg starting dose and placebo -2.0 days (95% CI: -3.84, -0.22). 
 
Approximately 52% of the patients in the study had acute headache medication overuse. The observed 
treatment difference for the reduction of monthly headache days (MHD) of at least moderate severity 
between fremanezumab 675 mg quarterly and placebo in these patients was -2.2 days (95% CI: -3.14, 
-1.22) and between fremanezumab 225 mg monthly with 675 mg starting dose and placebo -2.7 days 
(95% CI: -3.71, -1.78). 
 
Long-term study (Study 3) 
For all episodic and chronic migraine patients, efficacy was sustained for up to 12 additional months 
in the long-term study (Study 3), in which patients received 225 mg fremanezumab monthly or 
675 mg quarterly. 79% of patients completed the 12-month treatment period of Study 3. Pooled across 
the two dosing regimens, a reduction of 6.6 monthly migraine days was observed after 15 months 
relative to Study 1 and Study 2 baseline. 61% of patients completing Study 3 achieved a 50% response 
in the last month of the study. No safety signal was observed during the 15-month combined treatment 
period. 
 
Intrinsic and extrinsic factors 
The efficacy and safety of fremanezumab was demonstrated regardless of age, gender, race, use of 
concomitant preventive medicinal products (beta-blockers, calcium channel 
blocker/benzocycloheptene, antidepressants, anticonvulsants), use of topiramate or 
onabotulinumtoxin A for migraine in the past, and acute headache medication overuse. 
There is limited data available on the use of fremanezumab in patients ≥65 years of age (2% of the 
patients). 
 
Paediatric population 
 
The European Medicines Agency has deferred the obligation to submit the results of studies with 
AJOVY in one or more subsets of the paediatric population in prevention of migraine headaches (see 
section 4.2 for information on paediatric use). 
 



11 
 

5.2 Pharmacokinetic properties 
 
Absorption 
 
After single subcutaneous administrations of 225 mg and 675 mg fremanezumab, median time to 
maximum concentrations (tmax) in healthy subjects was 5 to 7 days. The absolute bioavailability of 
fremanezumab after subcutaneous administration of 225 mg and 900 mg in healthy subjects was 55% 
(±SD of 23%) to 66% (±SD of 26%). Dose proportionality, based on population pharmacokinetics, 
was observed between 225 mg to 675 mg. Steady state was achieved by approximately 168 days 
(about 6 months) following 225 mg monthly and 675 mg quarterly dosing regimens. Median 
accumulation ratio, based on once monthly and once quarterly dosing regimens, is approximately 2.4 
and 1.2, respectively. 
 
Distribution 
 
Assuming the model-derived estimated bioavailability of 66% (±SD of 26%) holds for the patient 
population, the volume of distribution for a typical patient was 3.6 L (35.1% CV) following 
subcutaneous administration of 225 mg, 675 mg and 900 mg of fremanezumab. 
 
Biotransformation 
 
Similar to other monoclonal antibodies, fremanezumab is expected to be degraded by enzymatic 
proteolysis into small peptides and amino acids. 
 
Elimination 
 
Assuming the model-derived estimated bioavailability of 66% (±SD of 26%) holds for the patient 
population, central clearance for a typical patient was 0.09 L/day (23.4% CV) following subcutaneous 
administration of 225 mg, 675 mg and 900 mg of fremanezumab. The formed small peptides and 
amino acids may be re-used in the body for de novo synthesis of proteins or are excreted by the 
kidney. Fremanezumab has an estimated half-life of 30 days. 
 
Special populations 
 
A population pharmacokinetic analysis looking at age, race, gender, and weight was conducted on data 
from 2,546 subjects. Approximately twice as much exposure is expected in the lowest body weight 
quartile (43.5 to 60.5 kg) compared to the highest body weight quartile (84.4 to131.8 kg). However, 
body weight did not have an observed effect on the clinical efficacy based on the exposure-response 
analyses in episodic and chronic migraine patients. No dose adjustments are required for 
fremanezumab. No data on exposure-efficacy relationship in subjects with body weight >132 kg is 
available. 
 
Renal or hepatic impairment 
Since monoclonal antibodies are not known to be eliminated via renal pathways or metabolised in the 
liver, renal and hepatic impairment are not expected to impact the pharmacokinetics of fremanezumab. 
Patients with severe renal impairment (eGFR <30 mL/min/1.73 m2) have not been studied. Population 
pharmacokinetic analysis of integrated data from the AJOVY clinical studies did not reveal a 
difference in the pharmacokinetics of fremanezumab in patients with mild to moderate renal 
impairment or hepatic impairment relative to those with normal renal or hepatic function (see 
section 4.2). 
 



12 
 

5.3 Preclinical safety data 
 
Non-clinical data reveal no special hazard for humans based on conventional studies of safety 
pharmacology, repeated dose toxicity, toxicity to reproduction and development. 
 
As fremanezumab is a monoclonal antibody, no genotoxicity or carcinogenicity studies have been 
conducted. 
 
 
6. PHARMACEUTICAL PARTICULARS 
 
6.1 List of excipients 
 
L-histidine 
L-histidine hydrochloride monohydrate 
Sucrose 
Disodium ethylenediaminetetraacetic acid (EDTA) dihydrate  
Polysorbate 80 (E 433) 
Water for injections 
 
6.2 Incompatibilities 
 
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal 
products. 
 
6.3 Shelf life 
 
2 years 
 
6.4 Special precautions for storage 
 
Store in a refrigerator (2°C – 8°C). 
Do not freeze. 
Keep the pre-filled syringe(s) or pre-filled pen(s) in the outer carton in order to protect from light. 
AJOVY may be stored unrefrigerated for up to 24 hours at a temperature up to 25°C. AJOVY must be 
discarded if it has been out of the refrigerator for longer than 24 hours. 
 
6.5 Nature and contents of container 
 
Pre-filled syringe 
 
1.5 mL solution in a 2.25 mL Type I glass syringe with plunger stopper (bromobutyl rubber) and 
needle.  
 
Pack sizes of 1 or 3 pre-filled syringes. Not all pack sizes may be marketed. 
 
Pre-filled pen 
 
Pre-filled pen containing 1.5 mL solution in a 2.25 mL Type I glass syringe with plunger stopper 
(bromobutyl rubber) and needle. 
 
Pack sizes of 1 or 3 pre-filled pens. Not all pack sizes may be marketed. 
 



13 
 

6.6 Special precautions for disposal and other handling 
 
Instructions for use 
 
The detailed instructions for use provided at the end of the package leaflet must be followed step-by-
step carefully.  
The pre-filled syringe and the pre-filled pen are for single use only.  
AJOVY should not be used if the solution is cloudy or discoloured or contains particles. 
AJOVY should not be used if the solution has been frozen. 
The pre-filled syringe and the pre-filled pen should not be shaken. 
 
Disposal 
 
Any unused medicinal product or waste material should be disposed of in accordance with local 
requirements.  
 
 
7. MARKETING AUTHORISATION HOLDER 
 
TEVA GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
 
8. MARKETING AUTHORISATION NUMBER(S)  
 
Pre-filled syringe 
 
EU/1/19/1358/001 – 1 pre-filled syringe 
EU/1/19/1358/002 – 3 pre-filled syringes 
 
Pre-filled pen 
 
EU/1/19/1358/003 – 1 pre-filled pen 
EU/1/19/1358/004 – 3 pre-filled pens 
 
 
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION 
 
Date of first authorisation: 28 March 2019 
 
 
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. 

http://www.ema.europa.eu/


14 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX II 
 
A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 

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 
 
 
 



15 
 

A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 
MANUFACTURER(S) RESPONSIBLE FOR BATCH RELEASE 

 
Name and address of the manufacturer(s) of the biological active substance(s)  
 
CELLTRION Inc. 
20 Academy-ro 51 beon-gil 
Yeonsu-gu 
22014 Incheon 
Republic of Korea 
 
Name and address of the manufacturer(s) responsible for batch release 
 
Merckle GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5 
2031 GA Haarlem 
Netherlands 
 
The printed package leaflet of the medicinal product must state the name and address of the 
manufacturer responsible for the release of the concerned batch. 
 
 
B. CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE 
 
Medicinal product subject to restricted medical prescription. (see Annex I: Summary of Product 
Characteristics, section 4.2) 
 
 
C. OTHER CONDITIONS AND REQUIREMENTS OF THE MARKETING 

AUTHORISATION  
 
• Periodic safety update reports (PSURs) 
 
The requirements for submission of PSURs 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. 
 
The marketing authorisation holder (MAH) shall submit the first PSUR for this product within 6 
months following authorisation.  
 
 
D. CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND 

EFFECTIVE USE OF THE MEDICINAL PRODUCT 
 
• Risk management plan (RMP) 
 
The marketing authorisation holder 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: 



16 
 

• 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.  



17 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX III 
 

LABELLING AND PACKAGE LEAFLET 



18 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

A. LABELLING 



19 
 

 
PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – PRE-FILLED SYRINGE 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
AJOVY 225 mg solution for injection in pre-filled syringe  
fremanezumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled syringe contains 225 mg fremanezumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-histidine, L-histidine hydrochloride monohydrate, sucrose, disodium 
ethylenediaminetetraacetic acid (EDTA) dihydrate, polysorbate 80, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled syringe of 1.5 mL solution 
3 pre-filled syringes of 1.5 mL solution 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use 
For single use only. 
 
OPEN HERE 
LIFT HERE 
 
 
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 
 
AJOVY must be discarded if it has been out of the refrigerator for longer than 24 hours. 
 
 
8. EXPIRY DATE 
 
EXP 



20 
 

 
 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled syringe in the outer carton in order to protect from light. 
Keep the pre-filled syringes in the outer carton in order to protect from light. 
 
 
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 
 
TEVA GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1358/001 1 pre-filled syringe 
EU/1/19/1358/002 3 pre-filled syringes 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
AJOVY Syringe 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 



21 
 

18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



22 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED SYRINGE LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
AJOVY 225 mg injection 
fremanezumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.5 mL 
 
 
6. OTHER 
 
 
 
 



23 
 

PARTICULARS TO APPEAR ON THE OUTER PACKAGING 
 
OUTER CARTON – PRE-FILLED PEN 
 
 
1. NAME OF THE MEDICINAL PRODUCT 
 
AJOVY 225 mg solution for injection in pre-filled pen  
fremanezumab 
 
 
2. STATEMENT OF ACTIVE SUBSTANCE(S) 
 
One pre-filled pen contains 225 mg fremanezumab. 
 
 
3. LIST OF EXCIPIENTS 
 
Excipients: L-histidine, L-histidine hydrochloride monohydrate, sucrose, disodium 
ethylenediaminetetraacetic acid (EDTA) dihydrate, polysorbate 80, water for injections. 
 
 
4. PHARMACEUTICAL FORM AND CONTENTS 
 
Solution for injection 
1 pre-filled pen of 1.5 mL solution 
3 pre-filled pens of 1.5 mL solution 
 
 
5. METHOD AND ROUTE(S) OF ADMINISTRATION 
 
Read the package leaflet before use. 
Subcutaneous use 
For single use only. 
 
OPEN HERE 
LIFT HERE 
 
 
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 
 
AJOVY must be discarded if it has been out of the refrigerator for longer than 24 hours. 
 
 
8. EXPIRY DATE 
 
EXP 
 



24 
 

 
9. SPECIAL STORAGE CONDITIONS 
 
Store in a refrigerator. 
Do not freeze. 
Keep the pre-filled pen in the outer carton in order to protect from light. 
Keep the pre-filled pens in the outer carton in order to protect from light. 
 
 
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 
 
TEVA GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
 
12. MARKETING AUTHORISATION NUMBER(S)  
 
EU/1/19/1358/003 1 pre-filled pen 
EU/1/19/1358/004 3 pre-filled pens 
 
 
13. BATCH NUMBER 
 
Lot 
 
 
14. GENERAL CLASSIFICATION FOR SUPPLY 
 
 
15. INSTRUCTIONS ON USE 
 
 
16. INFORMATION IN BRAILLE 
 
AJOVY Pen 
 
 
17. UNIQUE IDENTIFIER – 2D BARCODE 
 
2D barcode carrying the unique identifier included. 
 
 
18. UNIQUE IDENTIFIER - HUMAN READABLE DATA 
 
PC 
SN 
NN 



25 
 

 
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS 
 
PRE-FILLED PEN LABEL 
 
 
1. NAME OF THE MEDICINAL PRODUCT AND ROUTE(S) OF ADMINISTRATION 
 
AJOVY 225 mg injection 
fremanezumab 
SC 
 
 
2. METHOD OF ADMINISTRATION 
 
 
3. EXPIRY DATE 
 
EXP 
 
 
4. BATCH NUMBER 
 
Lot 
 
 
5. CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT 
 
1.5 mL 
 
 
6. OTHER 
 
 
 
 



26 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

B. PACKAGE LEAFLET 



27 
 

Package leaflet: Information for the patient 
 

AJOVY 225 mg solution for injection in pre-filled syringe 
fremanezumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What AJOVY is and what it is used for  
2. What you need to know before you use AJOVY  
3. How to use AJOVY  
4. Possible side effects  
5. How to store AJOVY 
6. Contents of the pack and other information 
 
 
1. What AJOVY is and what it is used for 
 
What AJOVY is 
AJOVY is a medicine containing the active substance fremanezumab, a monoclonal antibody, a type 
of protein that recognises and attaches to a specific target in the body.  
 
How AJOVY works 
A substance in the body called calcitonin gene-related peptide (CGRP) plays an important role in 
migraine. Fremanezumab attaches to CGRP and prevents it from working. This reduction in CGRP's 
activity reduces migraine attacks. 
 
What AJOVY is used for 
AJOVY is used to prevent migraine in adults who have at least 4 migraine days per month. 
 
What are the benefits of using AJOVY 
AJOVY reduces the frequency of migraine attacks and days with headache. This medicine also 
decreases the disability associated with migraine and it reduces the need for medicines used to treat 
migraine attacks. 
 
 
2. What you need to know before you use AJOVY  
 
Do not use AJOVY 
Do not use this medicine if you are allergic to fremanezumab or any of the other ingredients of this 
medicine (listed in section 6).  
 



28 
 

Warnings and precautions  
Talk to your doctor, pharmacist or nurse if you get any symptoms of an allergic reaction, e.g. trouble 
breathing, swelling of the lips and tongue, or severe rash, after injecting AJOVY. 
 
Tell your doctor if you have or have had cardiovascular disease (problems affecting the heart and 
blood vessels) before using this medicine, because AJOVY has not been studied in patients with 
certain cardiovascular diseases. 
 
Children and adolescents 
AJOVY is not recommended for children and adolescents below the age of 18 years because it has not 
been studied in this age group. 
 
Other medicines and AJOVY 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. It is preferable to avoid the use of AJOVY during 
pregnancy as the effects of this medicine in pregnant women are not known. 
 
If you are breast-feeding or are planning to breast-feed, talk to your doctor or pharmacist before using 
this medicine. You and your doctor should decide if you will use AJOVY while breast-feeding.  
 
Driving and using machines 
This medicine is not expected to have any effect on your ability to drive or use machines. 
 
AJOVY contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially “sodium-free”. 
 
 
3. How to use AJOVY 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
AJOVY is given by injection under your skin (subcutaneous injection). Your doctor or nurse will 
explain to you or your caregiver how to give the injection. Do not inject AJOVY until you or your 
caregiver have been trained by your doctor or nurse. 
 
Read the “Instructions for Use” for the pre-filled syringe carefully before using AJOVY. 
 
How much and when to inject 
Your doctor will discuss and decide with you the most appropriate dosing schedule. There are two 
alternative recommended dosing options: 

- one injection (225 mg) once a month (monthly dosing) or 
- three injections (675 mg) every 3 months (quarterly dosing) 

 
If your dose is 675 mg, inject the three injections one after another, each in a different place. 
 
Use a reminder method such as notes in a calendar or diary to help you remember your next dose so 
that you do not miss a dose or have a dose too soon after the last one. 
 
If you use more AJOVY than you should 
If you have used more AJOVY than you should, tell your doctor. 
 



29 
 

If you forget or miss to use AJOVY 
If you have missed a dose of AJOVY, inject your missed dose as soon as you can. Do not take a 
double dose to make up for a forgotten dose. If you are not sure when to inject AJOVY, talk to your 
doctor, pharmacist or nurse. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following mild to moderate, short-lasting skin reactions around the injection area can occur: 
 
Very common (may affect more than 1 in 10 people) 
Pain, hardening or redness at the injection site 
 
Common (may affect up to 1 in 10 people) 
Itching at the injection site 
 
Uncommon (may affect up to 1 in 100 people) 
Rash at the injection site 
Allergic reactions such as rash, swelling or hives (see section 2) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store AJOVY 
 
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 syringe label and on the outer 
carton after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Keep the pre-filled syringe in the outer carton to protect the medicine from light. 
 
This medicine may be removed from the refrigerator and stored at a temperature below 25°C for a 
maximum period of up to 24 hours. The medicine must be discarded if it has been out of the 
refrigerator for longer than 24 hours. 
 
Do not use this medicine if you notice that the outer carton has been tampered with, the syringe is 
damaged, or the medicine is cloudy, discoloured, or contains particles. 
 
The syringe is for single use only. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

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


30 
 

6. Contents of the pack and other information 
 
What AJOVY contains  
- The active substance is fremanezumab.  

Each pre-filled syringe contains 225 mg of fremanezumab. 
- The other ingredients (excipients) are L-histidine, L-histidine hydrochloride monohydrate, 

sucrose, disodium ethylenediaminetetraacetic acid (EDTA) dihydrate, polysorbate 80 and water 
for injections. 

 
What AJOVY looks like and contents of the pack 
AJOVY is a solution for injection (injection) in a pre-filled syringe with a fixed injection needle in a 
blister. AJOVY is a clear, colourless to slightly yellow solution. Each pre-filled syringe contains 
1.5 mL solution. 
 
AJOVY is available in packs containing 1 or 3 pre-filled syringes. Not all pack sizes may be available 
in your country. 
 
Marketing Authorisation Holder  
TEVA GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
Manufacturer 
Merckle GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG 
Tél/Tel: +32 3 820 73 73  
 

Lietuva 
UAB Sicor Biotech 
Tel: +370 5 266 02 03 
 

България 
Актавис ЕАД  
Teл.: + 359 2 489 95 85 
 

Luxembourg/Luxemburg 
TEVA GmbH 
Allemagne/Deutschland 
Tél/Tel: +49 731 402 08  
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o. 
Tel: +420 251 007 111 

Magyarország 
Teva Gyógyszergyár Zrt.  
Tel.: +36 1 288 6400  



31 
 

Danmark 
Teva Denmark A/S  
Tlf: +45 44 98 55 11  
 

Malta 
Teva Pharmaceuticals Ireland  
L-Irlanda  
Tel: +353 51 321740  
 

Deutschland 
TEVA GmbH 
Tel: +49 731 402 08  
 

Nederland 
Teva Nederland B.V.  
Tel: +31 800 022 8400  
 

Eesti 
UAB Sicor Biotech Eesti filiaal  
Tel: +372 661 0801  
 

Norge 
Teva Norway AS  
Tlf: +47 66 77 55 90  
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH  
Tel: +43 1 97 007 0 
 

España 
Teva Pharma, S.L.U.  
Tél: +34 91 387 32 80  

Polska 
Teva Pharmaceuticals Polska Sp. z o.o.  
Tel.: +48 22 345 93 00  
 

France 
Teva Santé  
Tél: +33 1 55 91 78 00  
 

Portugal 
Teva Pharma - Produtos Farmacêuticos, Lda  
Tel: +351 21 476 75 50  

Hrvatska 
Pliva Hrvatska d.o.o.  
Tel: +385 1 37 20 000  
 
Ireland 
Teva Pharmaceuticals Ireland  
Tel: +353 51 321740 
 

România 
Teva Pharmaceuticals S.R.L. 
Tel: +40 21 230 65 24  
 
Slovenija 
Pliva Ljubljana d.o.o.  
Tel: +386 1 58 90 390  

Ísland 
Actavis Pharmaceuticals Iceland ehf. 
Sími: +354 550 3300 
 

Slovenská republika 
TEVA Pharmaceuticals Slovakia s.r.o.  
Tel: +421 2 57 26 79 11  

Italia 
Teva Italia S.r.l.  
Tel: +39 02 89 17 98 1  

Suomi/Finland 
Teva Finland 
Puh/Tel: +358 20 180 5900  
 

Κύπρος 
Teva Ελλάς Α.Ε.  
Ελλάδα 
Τηλ: +30 210 72 79 099 
 

Sverige 
Teva Sweden AB  
Tel: +46 42 12 11 00  
 

Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 673 23 666  
 

United Kingdom 
Teva UK Limited  
Tel: +44 1977 628500  
 

  
This leaflet was last revised in {month YYYY}. 
 



32 
 

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



33 
 

Instructions for Use 
 

AJOVY 225 mg solution for injection in pre-filled syringe 
fremanezumab 

 
 
Before you use the AJOVY pre-filled syringe, read and carefully follow the step-by-step 
instructions. 

 
Important information: 

• The AJOVY pre-filled syringe is for single use only.  
• Each AJOVY pre-filled syringe contains 225 mg of fremanezumab. Depending on your dose 

you will need to use 1 pre-filled syringe or 3 pre-filled syringes. 
• AJOVY is injected under your skin (subcutaneous injection).You should not inject yourself 

until you have been trained by your doctor or nurse. 
• Carefully read the AJOVY package leaflet to learn more about your medicine. 
• Do not pull back on the plunger at any time as this can break the pre-filled syringe. 
• Do not shake the pre-filled syringe. 
• Put the carton back in the refrigerator immediately, if you have any unused pre-filled 

syringes in the carton. 

 
Parts of the AJOVY pre-filled syringe  

 
 

Step 1: Getting ready for an injection  

a) Gather the following supplies for your injection: 
− 1 or 3 AJOVY pre-filled syringes to enable 1 or 3 injections depending on your dose 
− 1 alcohol swab per injection 
− 1 gauze pad or cotton ball per injection 
− 1 sharps disposal or puncture-resistant container 

b) Place the supplies you have gathered on a clean, flat surface. 
c) Wait for 30 minutes to let AJOVY reach room temperature to reduce discomfort during 

injection.  
− Do not leave the pre-filled syringe in direct sunlight. 
− Do not warm up the pre-filled syringe using a microwave or any other heat source. 

d) Wash your hands with soap and water and dry well with a clean towel. 
e) Inspect your AJOVY pre-filled syringe. 

− Check the syringe label. Make sure the name AJOVY appears on the label. 
− Check that the medicine inside the syringe looks clear and is colourless to slightly 

yellow. 
− You may see small air bubbles in the pre-filled syringe. This is normal. 



34 
 

− Do not use the pre-filled syringe if you see any of the following: 
 The syringe looks damaged. 
 The expiration date has passed. 
 The medicine is cloudy, discoloured, or contains particles. 

 
f) Choose your injection area. 

− Choose an injection area from the following areas: 
 Your stomach area (abdomen), avoid about 5 cm around the belly button 
 The front of your thighs, about 5 cm above the knee and 5 cm below the 

groin 
 The back of your upper arms, in the fleshy areas of the upper back portion 

− If multiple injections are required, they may be given in the same or different area 
(abdomen, thigh, upper arm), but you should avoid injecting in exactly the same place. 

 
g) Clean your injection area. 

− Clean the chosen injection area using a new alcohol swab. 
− Wait 10 seconds to allow the skin to dry before injecting. 
− Do not inject AJOVY into an area that is tender, red, hot, bruised, hardened, tattooed 

or that has scars or stretch marks. 
 

Step 2: How to inject  

a) Pull the needle cap straight off and throw it away.  
− Do not put the needle cap back on the pre-filled syringe, to avoid injury and infection. 
− Do not touch the needle. 

 



35 
 

b) Inject by following the 4 steps below. 

1. Gently pinch up at 
least 2.5 cm of the skin 
that you have cleaned. 

2. Insert the needle into the 
pinched skin at a 45° to 
90° angle. 

3. Slowly 
push the 
plunger in. 

4. Push the 
plunger all the 
way down as 
far as it will go 
to inject all of 
the medicine. 

 

 

c) Remove the needle from your skin. 
− After you have injected all of the medicine, pull the needle straight out. 
− Do not put the cap back on the needle at any time to avoid injury and infection. 

 

d) Apply pressure at the injection site. 
− Use a clean, dry cotton ball, or gauze to gently press on the injection site for a few 

seconds. 
− Do not rub the injection site or re-use the pre-filled syringe. 

 
 
Step 3: Disposal of the pre-filled syringe  

a) Dispose of your pre-filled syringe right away. 
− Put your used pre-filled syringes (with the needle still attached) in a sharps disposal 

container right away after use.  
− Do not throw away (dispose of) loose needles, syringes, or pre-filled syringes with 

your household waste.  
− Do not recycle used sharps disposal container. 

b) Ask your doctor, pharmacist or nurse how to throw away the container.  
 
 
If your dose is 675 mg, repeat steps 1 e) to 3 a) with the second and third pre-filled 
syringe to inject the full dose. 
 



36 
 

Package leaflet: Information for the patient 
 

AJOVY 225 mg solution for injection in pre-filled pen 
fremanezumab 

 
This medicine is subject to additional monitoring. This will allow quick identification of new 

safety information. You can help by reporting any side effects you may get. See the end of section 4 
for how to report side effects. 
 
Read all of this leaflet carefully before you start using this medicine because it contains 
important information for you. 
- Keep this leaflet. You may need to read it again.  
- If you have any further questions, ask your doctor, pharmacist or nurse. 
- This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, 

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

side effects not listed in this leaflet. See section 4. 
 
What is in this leaflet 
 
1. What AJOVY is and what it is used for  
2. What you need to know before you use AJOVY  
3. How to use AJOVY  
4. Possible side effects  
5. How to store AJOVY 
6. Contents of the pack and other information 
 
 
1. What AJOVY is and what it is used for 
 
What AJOVY is 
AJOVY is a medicine containing the active substance fremanezumab, a monoclonal antibody, a type 
of protein that recognises and attaches to a specific target in the body.  
 
How AJOVY works 
A substance in the body called calcitonin gene-related peptide (CGRP) plays an important role in 
migraine. Fremanezumab attaches to CGRP and prevents it from working. This reduction in CGRP's 
activity reduces migraine attacks. 
 
What AJOVY is used for 
AJOVY is used to prevent migraine in adults who have at least 4 migraine days per month. 
 
What are the benefits of using AJOVY 
AJOVY reduces the frequency of migraine attacks and days with headache. This medicine also 
decreases the disability associated with migraine and it reduces the need for medicines used to treat 
migraine attacks. 
 
 
2. What you need to know before you use AJOVY  
 
Do not use AJOVY 
Do not use this medicine if you are allergic to fremanezumab or any of the other ingredients of this 
medicine (listed in section 6).  
 



37 
 

Warnings and precautions  
Talk to your doctor, pharmacist or nurse if you get any symptoms of an allergic reaction, e.g. trouble 
breathing, swelling of the lips and tongue, or severe rash, after injecting AJOVY. 
 
Tell your doctor if you have or have had cardiovascular disease (problems affecting the heart and 
blood vessels) before using this medicine, because AJOVY has not been studied in patients with 
certain cardiovascular diseases. 
 
Children and adolescents 
AJOVY is not recommended for children and adolescents below the age of 18 years because it has not 
been studied in this age group. 
 
Other medicines and AJOVY 
Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. 
 
Pregnancy and breast-feeding 
If you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or 
pharmacist for advice before taking this medicine. It is preferable to avoid the use of AJOVY during 
pregnancy as the effects of this medicine in pregnant women are not known. 
 
If you are breast-feeding or are planning to breast-feed, talk to your doctor or pharmacist before using 
this medicine. You and your doctor should decide if you will use AJOVY while breast-feeding.  
 
Driving and using machines 
This medicine is not expected to have any effect on your ability to drive or use machines. 
 
AJOVY contains sodium 
This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially “sodium-free”. 
 
 
3. How to use AJOVY 
 
Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor 
or pharmacist if you are not sure.  
 
AJOVY is given by injection under your skin (subcutaneous injection). Your doctor or nurse will 
explain to you or your caregiver how to give the injection. Do not inject AJOVY until you or your 
caregiver have been trained by your doctor or nurse. 
 
Read the “Instructions for Use” for the pre-filled pen carefully before using AJOVY. 
 
How much and when to inject 
Your doctor will discuss and decide with you the most appropriate dosing schedule. There are two 
alternative recommended dosing options: 

- one injection (225 mg) once a month (monthly dosing) or 
- three injections (675 mg) every 3 months (quarterly dosing) 

 
If your dose is 675 mg, inject the three injections one after another, each in a different place. 
 
Use a reminder method such as notes in a calendar or diary to help you remember your next dose so 
that you do not miss a dose or have a dose too soon after the last one. 
 
If you use more AJOVY than you should 
If you have used more AJOVY than you should, tell your doctor. 
 



38 
 

If you forget or miss to use AJOVY 
If you have missed a dose of AJOVY, inject your missed dose as soon as you can. Do not take a 
double dose to make up for a forgotten dose. If you are not sure when to inject AJOVY, talk to your 
doctor, pharmacist or nurse. 
 
If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse. 
 
 
4. Possible side effects 
 
Like all medicines, this medicine can cause side effects, although not everybody gets them. 
 
The following mild to moderate, short-lasting skin reactions around the injection area can occur: 
 
Very common (may affect more than 1 in 10 people) 
Pain, hardening or redness at the injection site 
 
Common (may affect up to 1 in 10 people) 
Itching at the injection site 
 
Uncommon (may affect up to 1 in 100 people) 
Rash at the injection site 
Allergic reactions such as rash, swelling or hives (see section 2) 
 
Reporting of side effects 
If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side 
effects not listed in this leaflet. You can also report side effects directly via the national reporting 
system listed in Appendix V. By reporting side effects you can help provide more information on the 
safety of this medicine. 
 
 
5. How to store AJOVY 
 
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 pen label and on the outer carton 
after EXP. The expiry date refers to the last day of that month. 
 
Store in a refrigerator (2°C – 8°C). Do not freeze. 
Keep the pre-filled pen in the outer carton to protect the medicine from light. 
 
This medicine may be removed from the refrigerator and stored at a temperature below 25°C for a 
maximum period of up to 24 hours. The medicine must be discarded if it has been out of the 
refrigerator for longer than 24 hours. 
 
Do not use this medicine if you notice that the outer carton has been tampered with, the pen is 
damaged, or the medicine is cloudy, discoloured, or contains particles. 
 
The pen is for single use only. 
 
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to 
throw away medicines you no longer use. These measures will help protect the environment. 
 
 

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


39 
 

6. Contents of the pack and other information 
 
What AJOVY contains  
- The active substance is fremanezumab.  

Each pre-filled pen contains 225 mg of fremanezumab. 
- The other ingredients (excipients) are L-histidine, L-histidine hydrochloride monohydrate, 

sucrose, disodium ethylenediaminetetraacetic acid (EDTA) dihydrate, polysorbate 80 and water 
for injections. 

 
What AJOVY looks like and contents of the pack 
AJOVY is a solution for injection (injection) in a single-dose pre-filled pen. AJOVY is a clear, 
colourless to slightly yellow solution. Each pre-filled pen contains 1.5 mL solution. 
 
AJOVY is available in packs containing 1 or 3 pre-filled pens. Not all pack sizes may be available in 
your country. 
 
Marketing Authorisation Holder  
TEVA GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
Manufacturer 
Merckle GmbH 
Graf-Arco-Str. 3 
89079 Ulm 
Germany 
 
Teva Pharmaceuticals Europe B.V. 
Swensweg 5 
2031 GA Haarlem 
The Netherlands 
 
For any information about this medicine, please contact the local representative of the Marketing 
Authorisation Holder: 
 
België/Belgique/Belgien 
Teva Pharma Belgium N.V./S.A./AG 
Tél/Tel: +32 3 820 73 73  
 

Lietuva 
UAB Sicor Biotech 
Tel: +370 5 266 02 03 
 

България 
Актавис ЕАД  
Teл.: + 359 2 489 95 85 
 

Luxembourg/Luxemburg 
TEVA GmbH 
Allemagne/Deutschland 
Tél/Tel: +49 731 402 08  
 

Česká republika 
Teva Pharmaceuticals CR, s.r.o. 
Tel: +420 251 007 111 

Magyarország 
Teva Gyógyszergyár Zrt.  
Tel.: +36 1 288 6400  



40 
 

Danmark 
Teva Denmark A/S  
Tlf: +45 44 98 55 11  
 

Malta 
Teva Pharmaceuticals Ireland  
L-Irlanda  
Tel: +353 51 321740  
 

Deutschland 
TEVA GmbH 
Tel: +49 731 402 08  
 

Nederland 
Teva Nederland B.V.  
Tel: +31 800 022 8400  
 

Eesti 
UAB Sicor Biotech Eesti filiaal  
Tel: +372 661 0801  
 

Norge 
Teva Norway AS  
Tlf: +47 66 77 55 90  
 

Ελλάδα 
Teva Ελλάς Α.Ε. 
Τηλ: +30 210 72 79 099 

Österreich 
ratiopharm Arzneimittel Vertriebs-GmbH  
Tel: +43 1 97 007 0 
 

España 
Teva Pharma, S.L.U.  
Tél: +34 91 387 32 80  

Polska 
Teva Pharmaceuticals Polska Sp. z o.o.  
Tel.: +48 22 345 93 00  
 

France 
Teva Santé  
Tél: +33 1 55 91 78 00  
 

Portugal 
Teva Pharma - Produtos Farmacêuticos, Lda  
Tel: +351 21 476 75 50  

Hrvatska 
Pliva Hrvatska d.o.o.  
Tel: +385 1 37 20 000  
 
Ireland 
Teva Pharmaceuticals Ireland  
Tel: +353 51 321740 
 

România 
Teva Pharmaceuticals S.R.L. 
Tel: +40 21 230 65 24  
 
Slovenija 
Pliva Ljubljana d.o.o.  
Tel: +386 1 58 90 390  

Ísland 
Actavis Pharmaceuticals Iceland ehf. 
Sími: +354 550 3300 
 

Slovenská republika 
TEVA Pharmaceuticals Slovakia s.r.o.  
Tel: +421 2 57 26 79 11  

Italia 
Teva Italia S.r.l.  
Tel: +39 02 89 17 98 1  

Suomi/Finland 
Teva Finland 
Puh/Tel: +358 20 180 5900  
 

Κύπρος 
Teva Ελλάς Α.Ε.  
Ελλάδα 
Τηλ: +30 210 72 79 099 
 

Sverige 
Teva Sweden AB  
Tel: +46 42 12 11 00  
 

Latvija 
UAB Sicor Biotech filiāle Latvijā  
Tel: +371 673 23 666  
 

United Kingdom 
Teva UK Limited  
Tel: +44 1977 628500  
 

  
This leaflet was last revised in {month YYYY}. 
 



41 
 

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



42 
 

Instructions for Use 
 

AJOVY 225 mg solution for injection in pre-filled pen 
fremanezumab 

 
 
Before you use the AJOVY pre-filled pen, read and carefully follow the step-by-step 
instructions. 

 
Important information: 

• The AJOVY pre-filled pen is for single use only.  
• Each AJOVY pre-filled pen contains 225 mg of fremanezumab. Depending on your dose you 

will need to use 1 pre-filled pen or 3 pre-filled pens. 
• AJOVY is injected under your skin (subcutaneous injection). You should not inject yourself 

until you have been trained by your doctor or nurse. 
• Carefully read the AJOVY package leaflet to learn more about your medicine. 
• Do not shake the pre-filled pen. 
• Put the carton back in the refrigerator immediately, if you have any unused pre-filled pens 

in the carton. 

 
AJOVY pre-filled pen (before use)  

 
 

AJOVY pre-filled pen (after use)  

          
 



43 
 

• The blue plunger moves down the viewing window during the injection. The blue plunger fills 
the window when the injection is complete. (Note: When the blue plunger has filled the 
viewing window you will still be able to see the grey stopper.)  

• When injecting AJOVY, hold the pre-filled pen so that your hand does not cover the viewing 
window. 

 

Step 1: Getting ready for an injection  

a) Gather the following supplies for your injection: 
− 1 or 3 AJOVY pre-filled pens to enable 1 or 3 injections depending on your dose 
− 1 alcohol swab per injection 
− 1 gauze pad or cotton ball per injection 
− 1 sharps disposal or puncture-resistant container 

b) Place the supplies you have gathered on a clean, flat surface. 
c) Wait for 30 minutes to let AJOVY reach room temperature (<30°C) to reduce 

discomfort during injection.  
− Do not leave the pre-filled pen in direct sunlight. 
− Do not warm up the pre-filled pen using a microwave or any other heat source. 

d) Wash your hands with soap and water and dry well with a clean towel. 
e) Inspect your AJOVY pre-filled pen. 

− Check the pen label. Make sure the name AJOVY appears on the label. 
− Check that the medicine in the pen viewing window looks clear and is colourless to 

slightly yellow. 
− You may see small air bubbles in the pre-filled pen. This is normal. 
− Do not use the pre-filled pen if you see any of the following: 

 The pen looks damaged. 
 The expiration date has passed or if the pre-filled pen has been out of the 

refrigerator for longer than 24 hours. 
 The medicine is cloudy, discoloured, or contains particles. 

 

 
 

f) Choose your injection area. 
− Choose an injection area from the following areas: 

 Your stomach area (abdomen), avoid about 5 cm around the belly button 
 The front of your thighs, about 5 cm above the knee and 5 cm below the groin 
 The back of your upper arms, in the fleshy areas of the upper back portion 

− If multiple injections are required, they may be given in the same or different area 
(abdomen, thigh, upper arm), but you should avoid injecting in exactly the same place. 



44 
 

 
g) Clean your injection area. 

− Clean the chosen injection area using a new alcohol swab. 
− Wait 10 seconds to allow the skin to dry before injecting. 
− Do not inject AJOVY into an area that is tender, red, hot, bruised, hardened, tattooed 

or that has scars or stretch marks. 
 

Step 2: How to inject  

a) Remove the protective cap and do not replace.  
− Pull the protective cap straight off. Do not twist. 
− Do not put the protective cap back on the pre-filled pen, to avoid injury and infection. 
− Do not touch the needle shield area. 

 

b) Inject by following the steps below. 
− Place the pre-filled pen at a 90° angle against your skin at the injection site. 

 

 
 

− Press down on the pre-filled pen and keep pressed down against the skin for about 30 
seconds. Do not remove pressure until the 3 steps below are complete. 

 



45 
 

1. You hear the first 
“click” (this signals 
the start of the 
injection and the blue 
plunger starts to 
move). 

2. You hear a second “click” 
(about 15 seconds after the 
first “click”; the plunger 
will be moving to the 
bottom of the viewing 
window as the medicine is 
being injected). 

3. You wait another 10 seconds 
(to make sure all of the 
medicine is injected). 

 
 
 

c) Check that the blue plunger has filled the viewing window and remove the pre-filled pen 
from your skin. 

− After you have injected all of the medicine, i.e. the blue plunger has filled the viewing 
window and you are able to see the grey stopper, remove the pre-filled pen from the 
skin by lifting the pre-filled pen straight up and dispose straightaway into a sharp 
disposal container (see step 3). 

− As the pre-filled pen is lifted from the skin, the needle shield returns to the original 
position and locks into place, covering the needle. 

− Do not put the protective cap back on the pre-filled pen at any time to avoid injury 
and infection. 

 
 

d) Apply pressure at the injection site. 
− Use a clean, dry cotton ball, or gauze to gently press on the injection site for a few 

seconds. 
− Do not rub the injection site or re-use the pre-filled pen. 

 
 



46 
 

Step 3: Disposal of the pre-filled pen  

a) Dispose of your pre-filled pen right away. 
− Put your used pre-filled pens in a sharps disposal container right away after use.  
− Do not throw away (dispose of) pre-filled pens with your household waste.  
− Do not recycle used sharps disposal container. 

b) Ask your doctor, pharmacist or nurse how to throw away the container.  
 
 
If your dose is 675 mg, repeat steps 1 e) to 3 a) with the second and third pre-filled pen 
to inject the full dose. 



47 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

ANNEX IV 
 

SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS 
OF THE MARKETING AUTHORISATION(S) 



48 
 

Scientific conclusions 
 
Taking into account the PRAC Assessment Report on the PSUR(s) for fremanezumab, the scientific 
conclusions of CHMP are as follows: 
 
In view of available data from clinical trials and spontaneous reports, the PRAC considers that a 
causal relationship between fremanezumab and hypersensitivity reactions, including urticaria, 
pruritus, rash and swelling/oedema is at least a reasonable possibility and the product information 
should be amended accordingly. 
 
The CHMP agrees with the scientific conclusions made by the PRAC. 
 
 
Grounds for the variation to the terms of the marketing authorisation(s) 
 
On the basis of the scientific conclusions for fremanezumab the CHMP is of the opinion that the 
benefit-risk balance of the medicinal product(s) containing fremanezumab is unchanged subject to 
the proposed changes to the product information 
 
The CHMP recommends that the terms of the marketing authorisation(s) should be varied. 

 


	SUMMARY OF PRODUCT CHARACTERISTICS
	A. MANUFACTURER(S) OF THE BIOLOGICAL ACTIVE SUBSTANCE(S) AND 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
	SCIENTIFIC CONCLUSIONS AND GROUNDS FOR THE VARIATION TO THE TERMS OF THE MARKETING AUTHORISATION(S)
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{'Title': '2. what you need to know before you use ajovy', 'Section_Content': 'do not use ajovy do not use this medicine if you are allergic to fremanezumab or any of the other ingredients of this medicine (listed in section 6). warnings and precautions talk to your doctor, pharmacist or nurse if you get any symptoms of an allergic reaction, e.g. trouble breathing, swelling of the lips and tongue, or severe rash, after injecting ajovy. tell your doctor if you have or have had cardiovascular disease (problems affecting the heart and blood vessels) before using this medicine, because ajovy has not been studied in patients with certain cardiovascular diseases. children and adolescents ajovy is not recommended for children and adolescents below the age of 18 years because it has not been studied in this age group. other medicines and ajovy tell your doctor or pharmacist if you are using, have recently used or might use any other medicines. pregnancy and breast-feeding if you are pregnant, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine. it is preferable to avoid the use of ajovy during pregnancy as the effects of this medicine in pregnant women are not known. if you are breast-feeding or are planning to breast-feed, talk to your doctor or pharmacist before using this medicine. you and your doctor should decide if you will use ajovy while breast-feeding. driving and using machines this medicine is not expected to have any effect on your ability to drive or use machines. ajovy contains sodium this medicine contains less than 1 mmol sodium (23 mg) per dose, i.e. is essentially "sodium-free".', 'Entity_Recognition': [{'Text': 'ajovy', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 28, 'EndOffset': 41}, {'Text': 'allergic', 'Type': 'PROBLEM', 'BeginOffset': 53, 'EndOffset': 61}, {'Id': 5, 'BeginOffset': 65, 'EndOffset': 77, 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0.8466722965240479}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.3472312092781067, 'RelationshipScore': 0.4861091077327728, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 2, 'BeginOffset': 402, 'EndOffset': 416, 'Text': 'cardiovascular', 'Category': 'ANATOMY', 'Traits': []}, {'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9782861471176147, 'RelationshipScore': 0.9563721418380737, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 3, 'BeginOffset': 449, 'EndOffset': 454, 'Text': 'heart', 'Category': 'ANATOMY', 'Traits': []}, {'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9531176090240479, 'RelationshipScore': 0.9830406308174133, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 4, 'BeginOffset': 459, 'EndOffset': 472, 'Text': 'blood vessels', 'Category': 'ANATOMY', 'Traits': []}]}, {'Id': 3, 'BeginOffset': 449, 'EndOffset': 454, 'Score': 0.9782861471176147, 'Text': 'heart', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 4, 'BeginOffset': 459, 'EndOffset': 472, 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{'Title': '3. how to use ajovy', 'Section_Content': 'always use this medicine exactly as your doctor or pharmacist has told you. check with your doctor or pharmacist if you are not sure. ajovy is given by injection under your skin (subcutaneous injection). your doctor or nurse will explain to you or your caregiver how to give the injection. do not inject ajovy until you or your caregiver have been trained by your doctor or nurse. read the "instructions for use" for the pre-filled syringe carefully before using ajovy. how much and when to inject your doctor will discuss and decide with you the most appropriate dosing schedule. there are two alternative recommended dosing options: - one injection (225 mg) once a month (monthly dosing) or - three injections (675 mg) every 3 months (quarterly dosing) if your dose is 675 mg, inject the three injections one after another, each in a different place. use a reminder method such as notes in a calendar or diary to help you remember your next dose so that you do not miss a dose or have a dose too soon after the last one. if you use more ajovy than you should if you have used more ajovy than you should, tell your doctor. if you forget or miss to use ajovy if you have missed a dose of ajovy, inject your missed dose as soon as you can. do not take a double dose to make up for a forgotten dose. if you are not sure when to inject ajovy, talk to your doctor, pharmacist or nurse. if you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.', 'Entity_Recognition': [{'Text': 'ajovy', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 11, 'EndOffset': 24}, {'Text': 'ajovy', 'Type': 'TREATMENT', 'BeginOffset': 134, 'EndOffset': 139}, {'Text': 'your skin (subcutaneous injection', 'Type': 'TREATMENT', 'BeginOffset': 168, 'EndOffset': 201}, {'Text': 'the injection', 'Type': 'TREATMENT', 'BeginOffset': 275, 'EndOffset': 288}, {'Text': 'the pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 417, 'EndOffset': 439}, {'Text': '675', 'Type': 'NUMBER', 'BeginOffset': 713, 'EndOffset': 716}, {'Text': '3', 'Type': 'NUMBER', 'BeginOffset': 727, 'EndOffset': 728}, {'Text': '675', 'Type': 'NUMBER', 'BeginOffset': 771, 'EndOffset': 774}, {'Text': 'a reminder method', 'Type': 'TREATMENT', 'BeginOffset': 857, 'EndOffset': 874}, {'Text': 'ajovy', 'Type': 'TREATMENT', 'BeginOffset': 1188, 'EndOffset': 1193}, {'Text': 'a double dose', 'Type': 'TREATMENT', 'BeginOffset': 1251, 'EndOffset': 1264}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 1430, 'EndOffset': 1443}]}
{'Title': '4. possible side effects', 'Section_Content': 'like all medicines, this medicine can cause side effects, although not everybody gets them. the following mild to moderate, short-lasting skin reactions around the injection area can occur: very common (may affect more than 1 in 10 people) pain, hardening or redness at the injection site common (may affect up to 1 in 10 people) itching at the injection site uncommon (may affect up to 1 in 100 people) rash at the injection site allergic reactions such as rash, swelling or hives (see section 2) reporting of side effects if you get any side effects, talk to your doctor, pharmacist or nurse. this includes any possible side effects not listed in this leaflet. you can also report side effects directly via the national reporting system listed in appendix v. by reporting side effects you can help provide more information on the safety of this medicine.', 'Entity_Recognition': [{'Text': 'ajovy', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'all medicines', 'Type': 'TREATMENT', 'BeginOffset': 5, 'EndOffset': 18}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 20, 'EndOffset': 33}, {'Id': 6, 'BeginOffset': 44, 'EndOffset': 56, 'Score': 0.9648535847663879, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7970803380012512}]}, {'Text': 'the following mild to moderate, short-lasting skin reactions', 'Type': 'PROBLEM', 'BeginOffset': 92, 'EndOffset': 152}, {'Id': 1, 'BeginOffset': 164, 'EndOffset': 178, 'Score': 0.8793744444847107, 'Text': 'injection area', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Id': 8, 'BeginOffset': 207, 'EndOffset': 213, 'Score': 0.38863298296928406, 'Text': 'affect', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.8793744444847107, 'RelationshipScore': 0.7784563899040222, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 1, 'BeginOffset': 164, 'EndOffset': 178, 'Text': 'injection area', 'Category': 'ANATOMY', 'Traits': []}]}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 224, 'EndOffset': 225}, {'Text': '10', 'Type': 'NUMBER', 'BeginOffset': 229, 'EndOffset': 231}, {'Id': 9, 'BeginOffset': 240, 'EndOffset': 244, 'Score': 0.9955354928970337, 'Text': 'pain', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8984715342521667}]}, {'Id': 10, 'BeginOffset': 246, 'EndOffset': 255, 'Score': 0.9209074974060059, 'Text': 'hardening', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8614394068717957}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9937008619308472, 'RelationshipScore': 0.8422574400901794, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 2, 'BeginOffset': 274, 'EndOffset': 288, 'Text': 'injection site', 'Category': 'ANATOMY', 'Traits': []}]}, {'Text': 'redness at the injection site', 'Type': 'PROBLEM', 'BeginOffset': 259, 'EndOffset': 288}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 314, 'EndOffset': 315}, {'Text': '10', 'Type': 'NUMBER', 'BeginOffset': 319, 'EndOffset': 321}, {'Id': 12, 'BeginOffset': 330, 'EndOffset': 337, 'Score': 0.9951801300048828, 'Text': 'itching', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8612115383148193}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9930859804153442, 'RelationshipScore': 0.9980727434158325, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 3, 'BeginOffset': 345, 'EndOffset': 359, 'Text': 'injection site', 'Category': 'ANATOMY', 'Traits': []}]}, {'Id': 3, 'BeginOffset': 345, 'EndOffset': 359, 'Score': 0.9930859804153442, 'Text': 'injection site', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 387, 'EndOffset': 388}, {'Text': '100', 'Type': 'NUMBER', 'BeginOffset': 392, 'EndOffset': 395}, {'Id': 13, 'BeginOffset': 404, 'EndOffset': 408, 'Score': 0.9952040910720825, 'Text': 'rash', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.6943314671516418}], 'Attributes': [{'Type': 'SYSTEM_ORGAN_SITE', 'Score': 0.9949495792388916, 'RelationshipScore': 0.951856791973114, 'RelationshipType': 'SYSTEM_ORGAN_SITE', 'Id': 4, 'BeginOffset': 416, 'EndOffset': 430, 'Text': 'injection site', 'Category': 'ANATOMY', 'Traits': []}]}, {'Text': 'the injection site', 'Type': 'PROBLEM', 'BeginOffset': 412, 'EndOffset': 430}, {'Id': 14, 'BeginOffset': 431, 'EndOffset': 449, 'Score': 0.668423593044281, 'Text': 'allergic reactions', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.7901573181152344}]}, {'Id': 15, 'BeginOffset': 458, 'EndOffset': 462, 'Score': 0.9990461468696594, 'Text': 'rash', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8884108662605286}]}, {'Id': 16, 'BeginOffset': 464, 'EndOffset': 472, 'Score': 0.9988616704940796, 'Text': 'swelling', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.9291306734085083}]}, {'Id': 17, 'BeginOffset': 476, 'EndOffset': 481, 'Score': 0.997576892375946, 'Text': 'hives', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.6808344125747681}]}, {'Text': '2', 'Type': 'NUMBER', 'BeginOffset': 495, 'EndOffset': 496}, {'Id': 18, 'BeginOffset': 511, 'EndOffset': 523, 'Score': 0.926146924495697, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.8270630240440369}]}, {'Id': 19, 'BeginOffset': 539, 'EndOffset': 551, 'Score': 0.9234601855278015, 'Text': 'side effects', 'Category': 'MEDICAL_CONDITION', 'Type': 'DX_NAME', 'Traits': [{'Name': 'SYMPTOM', 'Score': 0.803318440914154}]}, {'Id': 20, 'BeginOffset': 622, 'EndOffset': 634, 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{'Title': '5. how to store ajovy', 'Section_Content': 'keep this medicine out of the sight and reach of children. do not use this medicine after the expiry date which is stated on the syringe label and on the outer carton after exp. the expiry date refers to the last day of that month. store in a refrigerator (2 8). do not freeze. keep the pre-filled syringe in the outer carton to protect the medicine from light. this medicine may be removed from the refrigerator and stored at a temperature below 25 for a maximum period of up to 24 hours. the medicine must be discarded if it has been out of the refrigerator for longer than 24 hours. do not use this medicine if you notice that the outer carton has been tampered with, the syringe is damaged, or the medicine is cloudy, discoloured, or contains particles. the syringe is for single use only. do not throw away any medicines via wastewater or household waste. ask your pharmacist how to throw away medicines you no longer use. these measures will help protect the environment.', 'Entity_Recognition': [{'Text': 'ajovy', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 70, 'EndOffset': 83}, {'Text': 'the pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 283, 'EndOffset': 305}, {'Text': 'the outer carton', 'Type': 'TREATMENT', 'BeginOffset': 309, 'EndOffset': 325}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 362, 'EndOffset': 375}, {'Text': '25', 'Type': 'NUMBER', 'BeginOffset': 447, 'EndOffset': 449}, {'Text': '24', 'Type': 'NUMBER', 'BeginOffset': 480, 'EndOffset': 482}, {'Text': 'the medicine', 'Type': 'TREATMENT', 'BeginOffset': 490, 'EndOffset': 502}, {'Text': '24', 'Type': 'NUMBER', 'BeginOffset': 576, 'EndOffset': 578}, {'Text': 'this medicine', 'Type': 'TREATMENT', 'BeginOffset': 597, 'EndOffset': 610}, {'Text': 'cloudy', 'Type': 'PROBLEM', 'BeginOffset': 714, 'EndOffset': 720}, {'Text': 'the syringe', 'Type': 'TREATMENT', 'BeginOffset': 758, 'EndOffset': 769}]}
{'Title': '6. contents of the pack and other information', 'Section_Content': 'what ajovy contains - the active substance is fremanezumab. each pre-filled syringe contains 225 mg of fremanezumab. - the other ingredients (excipients) are l-histidine, l-histidine hydrochloride monohydrate, sucrose, disodium ethylenediaminetetraacetic acid (edta) dihydrate, polysorbate 80 and water for injections. what ajovy looks like and contents of the pack ajovy is a solution for injection (injection) in a pre-filled syringe with a fixed injection needle in a blister. ajovy is a clear, colourless to slightly yellow solution. each pre-filled syringe contains 1.5 ml solution. ajovy is available in packs containing 1 or 3 pre-filled syringes. not all pack sizes may be available in your country.', 'Entity_Recognition': [{'Text': 'ajovy', 'Type': 'PRODUCT_NAME', 'BeginOffset': 0, 'EndOffset': 0}, {'Id': 1, 'BeginOffset': 46, 'EndOffset': 58, 'Score': 0.9903924465179443, 'Text': 'fremanezumab', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.41326290369033813, 'RelationshipScore': 0.9930603504180908, 'RelationshipType': 'FORM', 'Id': 2, 'BeginOffset': 65, 'EndOffset': 92, 'Text': 'pre-filled syringe contains', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': 'each pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 60, 'EndOffset': 83}, {'Text': '225', 'Type': 'NUMBER', 'BeginOffset': 93, 'EndOffset': 96}, {'Id': 4, 'BeginOffset': 103, 'EndOffset': 115, 'Score': 0.9929458498954773, 'Text': 'fremanezumab', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'FORM', 'Score': 0.41326290369033813, 'RelationshipScore': 0.8168705105781555, 'RelationshipType': 'FORM', 'Id': 2, 'BeginOffset': 65, 'EndOffset': 92, 'Text': 'pre-filled syringe contains', 'Category': 'MEDICATION', 'Traits': []}, {'Type': 'DOSAGE', 'Score': 0.980628490447998, 'RelationshipScore': 0.9999974966049194, 'RelationshipType': 'DOSAGE', 'Id': 3, 'BeginOffset': 93, 'EndOffset': 99, 'Text': '225 mg', 'Category': 'MEDICATION', 'Traits': []}]}, {'Id': 5, 'BeginOffset': 158, 'EndOffset': 169, 'Score': 0.9906815886497498, 'Text': 'l-histidine', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 6, 'BeginOffset': 171, 'EndOffset': 208, 'Score': 0.9742343425750732, 'Text': 'l-histidine hydrochloride monohydrate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Id': 7, 'BeginOffset': 210, 'EndOffset': 217, 'Score': 0.690924346446991, 'Text': 'sucrose', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': []}, {'Text': 'disodium ethylenediaminetetraacetic acid (edta) dihydrate', 'Type': 'TREATMENT', 'BeginOffset': 219, 'EndOffset': 276}, {'Id': 10, 'BeginOffset': 278, 'EndOffset': 289, 'Score': 0.522967517375946, 'Text': 'polysorbate', 'Category': 'MEDICATION', 'Type': 'GENERIC_NAME', 'Traits': [], 'Attributes': [{'Type': 'ROUTE_OR_MODE', 'Score': 0.3393268883228302, 'RelationshipScore': 0.9999791383743286, 'RelationshipType': 'ROUTE_OR_MODE', 'Id': 11, 'BeginOffset': 307, 'EndOffset': 317, 'Text': 'injections', 'Category': 'MEDICATION', 'Traits': []}]}, {'Text': '80', 'Type': 'NUMBER', 'BeginOffset': 290, 'EndOffset': 292}, {'Text': 'injections', 'Type': 'TREATMENT', 'BeginOffset': 307, 'EndOffset': 317}, {'Text': 'a solution for injection (injection', 'Type': 'TREATMENT', 'BeginOffset': 375, 'EndOffset': 410}, {'Text': 'a pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 415, 'EndOffset': 435}, {'Text': 'a fixed injection needle', 'Type': 'TREATMENT', 'BeginOffset': 441, 'EndOffset': 465}, {'Text': 'a blister', 'Type': 'PROBLEM', 'BeginOffset': 469, 'EndOffset': 478}, {'Id': 0, 'BeginOffset': 480, 'EndOffset': 485, 'Score': 0.3316466510295868, 'Text': 'ajovy', 'Category': 'ANATOMY', 'Type': 'SYSTEM_ORGAN_SITE', 'Traits': []}, {'Text': 'slightly yellow solution', 'Type': 'PROBLEM', 'BeginOffset': 512, 'EndOffset': 536}, {'Text': 'each pre-filled syringe', 'Type': 'TREATMENT', 'BeginOffset': 538, 'EndOffset': 561}, {'Text': '1.5', 'Type': 'NUMBER', 'BeginOffset': 571, 'EndOffset': 574}, {'Text': '1', 'Type': 'NUMBER', 'BeginOffset': 627, 'EndOffset': 628}, {'Text': '3 pre-filled syringes', 'Type': 'TREATMENT', 'BeginOffset': 632, 'EndOffset': 653}]}