AJOVY

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 subcutaneous dosing options are available: • 225 mg once monthly (monthly dosing) or • 675 mg every three months (quarterly dosing), which is administered as three consecutive subcutaneous injections of 225 mg each. When switching dosing regimens, the first dose of the new regimen should be administered on the next scheduled dosing date of the prior regimen.

1). 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.

2). 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. 6.

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%]).

The adverse reactions that most commonly led to discontinuations were injection site reactions (1%). Table 1 summarizes adverse reactions reported in the 3-month placebo-controlled studies (Study 1 and Study 2), and the 1-month follow-up period after those studies.

Tabulated list of adverse reactions ADRs from clinical studies and post-marketing reports 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.

Table 1:

Adverse reactions occurring with an incidence of at least 2% for either dosing regimen of fremanezumab and at least 2% greater than placebo in Studies 1 and 2 Fremanezumab 225 mg Monthly (n = 290) % Fremanezumab 675 mg Quarterly (n = 667) % Placebo Monthly (n = 668) % Injection site reactionsa 43 45 38 a Injection site reactions include multiple related adverse event terms, such as injection site pain, induration and erythema.

The following ADRs have been identified for AJOVY (Table 2).

Table 2:

Adverse reactions MedDRA System Organ Class Frequency Adverse Reaction Immune system disorders Uncommon Hypersensitivity reactions such as rash, pruritus, urticaria and swelling Rare Anaphylactic reaction Injection site pain Injection site induration Very common Injection site erythema Common Injection site pruritus General disorders and administration site conditions Uncommon Injection site rash Description of selected adverse reactions Serious hypersensitivity reactions Anaphylactic reactions have been reported rarely.

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 reactions Hypersensitivity reactions, including rash, pruritus, drug hypersensitivity and urticaria, were reported with fremanezumab in clinical trials and in the post- marketing setting.

Most reactions were mild to moderate, but some led to discontinuation or required corticosteroid treatment. Most reactions were reported from within hours to one month after administration. 8). Most reactions have occurred within 24 hours of administration although some reactions have been delayed.

Patients should be warned about the symptoms associated with hypersensitivity reactions. 3). In the post-marketing period, one patient who was taking multiple concomitant medications including lamotrigine, and treated with fremanezumab, was reported to have Stevens-Johnson Syndrome.

This reaction has also been rarely reported to occur in patients taking other anti- CGRP monoclonal antibodies, along with concomitant medications including lamotrigine. If a hypersensitivity reaction occurs, discontinuation of fremanezumab administration should be considered and appropriate therapy should be initiated.

1). No safety data are available in these patients. , is essentially “sodium-free”.

1.