Rimegepant

Rimegepant is an oral calcitonin gene-related peptide receptor antagonist (gepant) used both for acute treatment of migraine and for prevention of episodic migraine. It is given as an orally disintegrating tablet, without vasoconstriction, and has a single 75 mg dose for both indications.

Mechanism. Blocks the calcitonin gene-related peptide receptor on trigeminal and meningeal vessels, preventing neurogenic vasodilation and pain signalling.

Pharmacokinetics. Bioavailability about 64% and protein binding about 96%. Peak is reached in about 1.5 hours and half-life is about 11 hours. It is metabolised by cytochrome P450 3A4 and 2C9.

Alternative use. Acute treatment of migraine, and preventive treatment of episodic migraine.

• Acute treatment, oral rimegepant: 75 mg once at onset. Maximum 75 mg in 24 hours. Safety of treating more than 18 attacks in 30 days is not established.

• Prevention: 75 mg every other day.

• With moderate cytochrome P450 3A4 inhibitors or P-glycoprotein inhibitors: avoid a second dose within 48 hours.

Kidney, liver, weight and age.

• Kidney: creatinine clearance under 15 mL/min, avoid. Otherwise no adjustment.

• Liver: severe impairment (Child-Pugh C), avoid. Mild to moderate, no adjustment.

• Older adults: limited data over age 65.

Contraindications. Hypersensitivity. Strong cytochrome P450 3A4 inhibitors are avoided, as are strong and moderate inducers.

Serious adverse effects. Hypersensitivity (dyspnoea, rash, sometimes delayed by days), hypertension and Raynaud phenomenon.

Common adverse effects. Nausea and, less often, abdominal pain and indigestion.

Interactions. Avoid strong cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) and strong or moderate inducers (rifampicin, carbamazepine, phenytoin, St John's wort). Moderate cytochrome P450 3A4 inhibitors and P-glycoprotein inhibitors limit repeat dosing.

Common prescribing errors. Treating a second attack within 24 hours. Prescribing with rifampicin or boosted protease inhibitors. Using for prevention and acute treatment on the same day without limits.

Special groups.

• Pregnancy: limited data; avoid unless clearly needed.

• Breastfeeding: no data; use with caution.

• Regional: costly and seldom available.

Formulations. Orally disintegrating tablets 75 mg, placed on or under the tongue without water.

Monitoring.

• Medicines review for interacting drugs, kidney and liver function, and blood pressure.

• Headache diary, with benefit reviewed after about 3 months of preventive use.

Stopping. No taper is needed.

Referral and escalation. Refer for poor response, frequent attacks, or suspected hypersensitivity.