Atogepant

Atogepant is an oral calcitonin gene-related peptide receptor antagonist used once daily for prevention of migraine. It does not treat an attack that has begun, and unlike monoclonal antibodies it needs daily dosing but clears quickly if stopped.

Mechanism. Blocks the calcitonin gene-related peptide receptor, reducing neurogenic inflammation and trigeminal pain signalling.

Pharmacokinetics. Peak is reached in 1 to 2 hours and half-life is about 11 hours. It is cleared by cytochrome P450 3A4 and is a substrate of organic anion transporting polypeptides and P-glycoprotein.

Alternative use. Preventive treatment of episodic migraine, and in some regions chronic migraine.

• Oral atogepant for episodic migraine: 10 mg, 30 mg or 60 mg once daily. Chronic migraine: 60 mg once daily.

• Strong cytochrome P450 3A4 inhibitors: episodic migraine 10 mg daily; chronic migraine 30 mg daily.

• Strong cytochrome P450 3A4 inducers: episodic migraine 30 or 60 mg daily; chronic migraine 60 mg daily.

• Organic anion transporting polypeptide inhibitors (ritonavir, cyclosporine, single-dose rifampicin): episodic migraine 10 mg daily; chronic migraine 30 mg daily.

• Review benefit after about 3 months.

Kidney, liver, weight and age.

• Kidney: creatinine clearance 15 to 29 mL/min, 10 mg daily for episodic and 30 mg daily for chronic migraine. End-stage disease, including haemodialysis, avoid.

• Liver: severe impairment, avoid. Mild to moderate, no adjustment.

• Older adults: limited data over age 65.

Contraindications. Hypersensitivity.

Serious adverse effects. Hypersensitivity reactions, hypertension and Raynaud phenomenon (uncommon).

Common adverse effects. Nausea, constipation, fatigue, reduced appetite and weight loss.

Interactions. Cytochrome P450 3A4 inhibitors and inducers and organic anion transporting polypeptide inhibitors change dose limits. Rifampicin and ritonavir regimens need review.

Common prescribing errors. Using it for acute attacks. Not adjusting for strong inhibitors. Prescribing in end-stage kidney disease.

Special groups.

• Pregnancy: avoid unless clearly needed.

• Breastfeeding: no data; use with caution.

• Regional: costly and seldom available.

Formulations. Tablets 10, 30 and 60 mg. Take once daily with or without food.

Monitoring.

• Baseline blood pressure, weight, kidney and liver function and a medicines review.

• Headache diary of monthly migraine days. Stop if there is no benefit by about 3 months.

Stopping. No taper is needed.

Referral and escalation. Refer for chronic migraine, failed preventive therapy, or suspected medication overuse headache.