4.1. Therapeutic indications

Emgality is indicated for the prophylaxis of migraine in adults who have at least 4 migraine days per month.

4.2. Posology and method of administration

Treatment should be initiated by physicians experienced in the diagnosis and treatment of migraine.

Posology

The recommended dose is 120 mg galcanezumab injected subcutaneously once monthly, with a 240 mg loading dose as the initial dose.

Patients should be instructed to inject a missed dose as soon as possible and then resume monthly dosing.

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.

Elderly (≥ 65 years)

There is limited information in subjects aged ≥ 65 years. No dose adjustment is required as the pharmacokinetics of galcanezumab are not affected by age.

Renal impairment/hepatic impairment

No dose adjustment is required in patients with mild to moderate renal impairment or hepatic impairment (see section 5.2).

Paediatric population

The safety and efficacy of galcanezumab in children aged 6 to 18 years have not yet been established. No data are available.

There is no relevant use of galcanezumab in children below the age of 6 years for the prevention of migraine.

Method of administration

Subcutaneous use.

A patient may self-inject galcanezumab by following the Instructions for Use. Galcanezumab is to be injected subcutaneously in the abdomen, thigh, back of the upper arm, or in the gluteal region. After training, patients may self-inject galcanezumab if a healthcare professional determines that it is appropriate. Comprehensive instructions for administration are given in the Package Leaflet.

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.

Cardiovascular risk

Patients with certain major cardiovascular diseases were excluded from clinical studies (see section 5.1). No safety data are available in these patients.

Serious hypersensitivity

Serious hypersensitivity reactions including cases of anaphylaxis, angioedema and urticaria have been reported (see section 4.8). Serious hypersensitivity reactions may occur within 1 day after galcanezumab administration, however cases with a delayed onset (ranging from more than 1 day to 4 weeks after administration) have been reported. In some cases, hypersensitivity reactions had a prolonged duration. If a serious hypersensitivity reaction occurs, administration of galcanezumab should be discontinued immediately and appropriate therapy initiated (see section 4.3). Patients should be informed on the possibility of a delayed onset hypersensitivity reaction and instructed to contact their physician.

Excipients

This medicine contains less than 1 mmol sodium (23 mg) per 120 mg dose, that is to say essentially “sodium-free”.

4.5. Interaction with other medicinal products and other forms of interaction

No drug interaction studies were conducted. No pharmacokinetic drug interactions are expected based on the characteristics of galcanezumab.

4.6. Fertility, pregnancy and lactation

Pregnancy

There are limited data from the use of galcanezumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). Human immunoglobulin (IgG) is known to cross the placental barrier. As a precautionary measure, it is preferable to avoid the use of galcanezumab during pregnancy.

Breast-feeding

It is unknown whether galcanezumab 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 galcanezumab could be considered during breast-feeding only if clinically needed.

Fertility

The effect of galcanezumab on human fertility has not been evaluated. Fertility studies in animals do not indicate harmful effects with respect to male and female fertility (see section 5.3).

4.7. Effects on ability to drive and use machines

Galcanezumab may have a minor influence on the ability to drive and use machines. Vertigo may occur following the administration of galcanezumab (see section 4.8).

4.8. Undesirable effects

Summary of the safety profile

Over 2 500 patients were exposed to galcanezumab in migraine prophylaxis studies supporting the initial registration of galcanezumab. Over 1 400 patients were exposed to galcanezumab during the double-blind treatment phase of the placebo-controlled phase 3 studies. 279 patients were exposed for 12 months.

The reported adverse drug reactions for 120 mg and 240 mg in the migraine clinical trials were injection site pain (10.1 %/11.6 %), injection site reactions (9.9 %/14.5 %), vertigo (0.7 %/1.2 %), constipation (1.0 %/1.5 %), pruritus (0.7 %/1.2 %) and urticaria (0.3 %/0.1 %). Most of the reactions were mild or moderate in severity. Less than 2.5 % of patients in these studies discontinued due to adverse reactions.

Tabulated list of adverse reactions

Table 1. List of adverse reactions in clinical studies and post-marketing reports

Frequency estimate: 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).

System organ class

Very common

Common

Uncommon

Rare

Immune system disorders

Anaphylaxis

Angioedema

Ear and labyrinth disorders

Vertigo

Gastrointestinal disorders

Constipation

Skin and subcutaneous tissue disorders

Pruritus

Rash

Urticaria

General disorders and administration site conditions

Injection site pain

Injection site reactionsa

a Most frequently reported terms (≥ 1 %) were: Injection site reaction, Injection site erythema, Injection site pruritus, Injection site bruising, Injection site swelling.

Description of selected adverse reactions

Injection site pain or reactions

The majority of reactions related to the injection site were mild to moderate and less than 0.5 % of patients exposed to galcanezumab during the phase 3 studies discontinued the treatment due to an injection site reaction. The majority of injection site reactions were reported within 1 day and on average resolved within 5 days. In 86 % of the patients reporting injection site pain, the reaction occurred within 1 hour of injection and resolved on average in 1 day. One percent of the patients exposed to galcanezumab during the phase 3 studies experienced severe pain at the injection site.

Urticaria

While urticaria is uncommon, serious cases of urticaria have been reported in galcanezumab clinical studies.

Immunogenicity

In the clinical studies, the incidence of anti-drug antibody development during the double-blind treatment phase was 4.8 % in patients receiving galcanezumab once monthly (all but one of whom had in vitro neutralizing activity). With 12 months of treatment, up to 12.5 % of galcanezumab-treated patients developed anti-drug antibodies, most of which were of low titre and tested positive for neutralising activity in vitro. However, the presence of anti-drug antibodies did not affect the pharmacokinetics, efficacy, or safety of galcanezumab.

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 Yellow Card Scheme, website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Doses up to 600 mg have been administered subcutaneously to humans without dose-limiting toxicity. In case of an overdose, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted immediately.