Galcanezumab

Galcanezumab is a humanised monoclonal antibody against the calcitonin gene-related peptide ligand, given monthly by subcutaneous injection for prevention of migraine, and in some regions for episodic cluster headache. It is one of the few preventive drugs with evidence in cluster headache.

Mechanism. Binds calcitonin gene-related peptide, preventing activation of its receptor and reducing trigeminal pain signalling.

Pharmacokinetics. Peak is reached in 5 days and half-life is about 27 days. It is cleared by general protein breakdown, so there are no cytochrome P450 or kidney interactions.

Specialist use. Preventive treatment of migraine in adults, and episodic cluster headache in adults.

• Migraine, subcutaneous galcanezumab: loading dose 240 mg (two 120 mg injections) once, then 120 mg once monthly. Review benefit after 3 months.

• Episodic cluster headache: 300 mg (three 100 mg injections) at the start of the cluster period, then 300 mg once monthly until the end of the cluster period. It is not effective for chronic cluster headache.

• After 6 to 12 months of good migraine control, consider a planned break from treatment.

Kidney, liver, weight and age.

• Kidney and liver: no adjustment.

• Older adults: limited data over age 65.

• Children: not licensed under 18 years.

Contraindications. Hypersensitivity.

Serious adverse effects. Hypersensitivity reactions (rash, angioedema, anaphylaxis), sometimes delayed by days to weeks. Hypertension, severe constipation and Raynaud phenomenon are reported.

Common adverse effects. Injection site reactions, pruritus and constipation.

Interactions. No clinically important interactions are described.

Common prescribing errors. Forgetting the loading dose in migraine. Using the migraine dose for cluster headache. Giving it for chronic cluster headache.

Special groups.

• Pregnancy: avoid unless clearly needed.

• Breastfeeding: no data; use with caution.

• Regional: very costly and seldom available, and cold storage is needed.

Formulations. Prefilled pen or syringe 120 mg in 1 mL (migraine) and 100 mg in 1 mL (cluster headache). Inject subcutaneously into the abdomen, thigh, upper arm or buttock. Store at 2 to 8 degrees Celsius, protected from light. It may be kept at room temperature for up to 7 days. Do not shake.

Monitoring.

• Baseline blood pressure and bowel habit, then blood pressure periodically.

• Headache diary of monthly migraine days or cluster attacks.

Stopping. No taper is needed. Effects wear off over several months.

Referral and escalation. Start under specialist care. Refer for hypersensitivity, poor response, or chronic cluster headache.