Fremanezumab

Fremanezumab is a humanised monoclonal antibody against the calcitonin gene-related peptide ligand, given by subcutaneous injection for prevention of migraine. It can be dosed monthly or every 3 months, and it is used when other preventive drugs have failed or were not tolerated.

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

Pharmacokinetics. Peak is reached in 5 to 7 days and half-life is about 31 days. It is cleared by general protein breakdown, not by cytochrome P450 enzymes or the kidney, so interactions and organ adjustments are not needed.

Specialist use. Preventive treatment of migraine in adults with at least 4 migraine days each month, after other preventive drugs have failed.

• Subcutaneous fremanezumab: 225 mg once monthly, or 675 mg once every 3 months (three 225 mg injections given at the same visit).

• If a dose is missed, give it as soon as possible and then continue the chosen schedule from that date.

• Review benefit after 3 months, and stop if there is no response by 3 to 6 months. After 6 to 12 months of good 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 in most regions.

Contraindications. Hypersensitivity.

Serious adverse effects. Hypersensitivity reactions (rash, itch, angioedema, anaphylaxis), sometimes delayed by days to weeks. New or worsening hypertension and Raynaud phenomenon are reported.

Common adverse effects. Injection site pain, induration and redness, and less often constipation.

Interactions. No clinically important interactions are described.

Common prescribing errors. Continuing without a benefit review. Missing hypertension. Combining with other calcitonin gene-related peptide antibodies.

Special groups.

• Pregnancy: avoid unless clearly needed, because the antibody crosses the placenta in later pregnancy.

• Breastfeeding: no data; use with caution.

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

Formulations. Prefilled syringe or autoinjector 225 mg in 1.5 mL. Inject subcutaneously into the abdomen, thigh or upper arm, rotating sites. Store at 2 to 8 degrees Celsius, protected from light. It may be kept at room temperature for up to 24 hours. Do not shake.

Monitoring.

• Baseline blood pressure, then periodically.

• Headache diary of monthly migraine days. Review at 3 months and about every 6 to 12 months.

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

Referral and escalation. Start under specialist care. Refer for hypersensitivity, severe hypertension or poor response.