Ubrogepant

Ubrogepant is an oral calcitonin gene-related peptide receptor antagonist (gepant) used for acute treatment of migraine with or without aura. It does not constrict blood vessels, so it is an option when triptans are contraindicated or ineffective, although data in vascular disease are limited. It is not used for prevention.

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

Pharmacokinetics. Peak is reached in about 1.5 hours and half-life is 5 to 7 hours. Protein binding about 87%. It is cleared mainly by cytochrome P450 3A4, and is a substrate of P-glycoprotein and breast cancer resistance protein.

Alternative use. Acute migraine attacks, when triptans are contraindicated, ineffective or not tolerated.

• Oral ubrogepant: 50 mg or 100 mg at onset. If needed, repeat one dose after at least 2 hours. Maximum 200 mg in 24 hours. Safety of treating more than 8 attacks in 30 days is not established.

• With moderate cytochrome P450 3A4 inhibitors (verapamil, diltiazem, fluconazole): 50 mg initial dose, and maximum 100 mg in 24 hours.

• With weak cytochrome P450 3A4 inhibitors or P-glycoprotein inhibitors: start 50 mg.

Kidney, liver, weight and age.

• Kidney: creatinine clearance 15 to 29 mL/min, 50 mg initial, with a second 50 mg dose if needed. Under 15 mL/min, avoid.

• Liver: severe impairment (Child-Pugh C), 50 mg initial, with a second 50 mg dose if needed. Mild to moderate impairment, no adjustment.

• Older adults: limited data over age 65.

Contraindications. Concurrent strong cytochrome P450 3A4 inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir) and hypersensitivity. Strong inducers (rifampicin, carbamazepine, phenytoin, St John's wort) are avoided because they remove efficacy.

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

Common adverse effects. Nausea, somnolence and dry mouth.

Interactions. Strong cytochrome P450 3A4 inhibitors are contraindicated. Strong inducers lower levels. Dose limits apply with moderate inhibitors.

Common prescribing errors. Using it for prevention. Taking more than 200 mg in 24 hours. Prescribing with boosted protease inhibitors or clarithromycin. Prescribing with rifampicin.

Special groups.

• Pregnancy: limited data; avoid unless clearly needed.

• Breastfeeding: no data; use with caution.

• Regional: costly and seldom available; antiretroviral and antituberculosis drug interactions need review.

Formulations. Tablets 50 and 100 mg. Take with or without food, at onset of headache.

Monitoring.

• Medicines review for cytochrome P450 3A4 inhibitors and inducers, and baseline kidney and liver function.

• Headache diary and blood pressure.

Stopping. No taper is needed.

Referral and escalation. Refer for frequent attacks needing prevention, or for poor response.