AJOVY Solution for injection Ref.[8745] Active ingredients: Fremanezumab

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 were reported with fremanezumab in less than 1% of patients in clinical trials. If a hypersensitivity reaction occurs, discontinuation of fremanezumab administration should be considered and appropriate therapy should be initiated.

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"

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.

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).

AJOVY has no or negligible influence on the ability to drive and use machines.

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%]).

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:

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.