Erenumab

Serious hypersensitivity reactions, including rash, angioedema, and anaphylactic reactions, have been reported with erenumab in post-marketing experience. These reactions may occur within minutes, although some may occur more than one week after treatment. In that context, patients should be warned about the symptoms associated with hypersensitivity reactions. If a serious or severe hypersensitivity reaction occurs, initiate appropriate therapy and do not continue treatment with erenumab.

There are a limited amount of data from the use of erenumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of erenumab during pregnancy.

It is unknown whether erenumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon afterwards; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, use of erenumab could be considered during breast-feeding only if clinically needed.

Fertility

Animal studies showed no impact on female and male fertility.

Erenumab is expected to have 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 2,600 patient years) have been treated with erenumab in registration studies. Of these, more than 1,300 patients were exposed for at least 12 months.

The reported adverse drug reactions for 70 mg and 140 mg were injection site reactions (5.6%/4.5%), constipation (1.3%/3.2%), muscle spasms (0.1%/2.0%) and pruritus (0.7%/1.8%). Most of the reactions were mild or moderate in severity. Less than 2% of patients in these studies discontinued due to adverse events.

List of adverse reactions

Below are listed all the adverse drug reactions that occurred in erenumab-treated patients during the 12-week placebo-controlled periods of the studies, as well as in the post-marketing setting. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse drug reaction is 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).

List of adverse reactions:

Immune system disorders

Common: Hypersensitivity reactions^a including anaphylaxis, angioedema, rash, swelling/oedema and urticaria

Gastrointestinal disorders

Common: Constipation

Skin and subcutaneous tissue disorders

Common: Pruritus^b

Musculoskeletal and connective tissue disorders

Common: Muscle spasms

General disorders and administration site conditions

Common: Injection site reactions^a

^a See section "Description of selected adverse reactions"
^b Pruritus includes preferred terms of generalised pruritus, pruritus and pruritic rash.

Description of selected adverse reactions

Injection site reactions

In the integrated 12-week placebo-controlled phase of the studies, injection site reactions were mild and mostly transient. There was one case of discontinuation in a patient receiving the 70 mg dose due to injection site rash. The most frequent injection site reactions were localised pain, erythema and pruritus. Injection site pain typically subsided within 1 hour after administration.

Cutaneous and hypersensitivity reactions

In the integrated 12-week placebo-controlled phase of the studies, non-serious cases of rash, pruritus and swelling/oedema were observed, which in the majority of cases were mild and did not lead to treatment discontinuation.

Cases of anaphylaxis and angiodoema were also observed in the post-marketing setting.

Immunogenicity

In the clinical studies, the incidence of anti-erenumab antibody development during the double-blind treatment phase was 6.3% (56/884) among subjects receiving a 70 mg dose of erenumab (3 of whom had in vitro neutralising activity) and 2.6% (13/504) among subjects receiving a 140 mg dose of erenumab (none of whom had in vitro neutralising activity). There was no impact of anti-erenumab antibody development on efficacy or safety.