Ubrelvy - Drug Monograph

Introduction

Ubrelvy (ubrogepant) is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved by the FDA in December 2019 for the acute treatment of migraine with or without aura in adults. It represents the first drug in its class specifically developed for migraine treatment, offering a novel mechanism of action distinct from traditional migraine medications.

Mechanism of Action

Ubrelvy works by selectively blocking the calcitonin gene-related peptide (CGRP) receptor. CGRP is a neuropeptide that plays a key role in migraine pathophysiology by mediating vasodilation, neurogenic inflammation, and pain transmission. By antagonizing the CGRP receptor, ubrogepant inhibits the physiological effects of CGRP, thereby aborting migraine attacks without causing vasoconstriction.

Indications

• Acute treatment of migraine with aura in adults
• Acute treatment of migraine without aura in adults

Not indicated for the preventive treatment of migraine.

Dosage and Administration

• Can be taken with or without food
• Maximum dose: 200 mg per 24-hour period
• If headache returns, a second dose may be taken after 2 hours

• Hepatic impairment: Avoid use in severe hepatic impairment; no dose adjustment needed for mild to moderate impairment
• Renal impairment: No dose adjustment needed
• Geriatric patients: Use with caution
• Pediatric patients: Safety and effectiveness not established

Pharmacokinetics

Contraindications

• Concomitant use with strong CYP3A4 inhibitors
• History of hypersensitivity to ubrogepant or any component of the formulation

Warnings and Precautions

• Hypersensitivity reactions, including facial swelling and urticaria, have been reported
• Avoid use in patients with severe hepatic impairment
• Use caution in patients with cardiovascular risk factors (though not vasoconstrictive, limited data in high-risk populations)
• Not recommended during pregnancy unless potential benefit justifies potential risk

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole): Contraindicated - increase ubrogepant exposure by ~6-fold
• Moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole): Avoid concomitant use
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease ubrogepant efficacy

Adverse Effects

• Nausea (4% vs 2% placebo)
• Somnolence (3% vs 1% placebo)
• Dry mouth (2% vs <1% placebo)

• Hypersensitivity reactions (rare)

Monitoring Parameters

• Migraine frequency and characteristics
• Response to treatment (pain freedom at 2 hours)
• Adverse effects, particularly nausea and somnolence
• Liver function tests in patients with hepatic impairment
• Signs of hypersensitivity reactions

Patient Education

• Take at the first sign of migraine symptoms
• Do not exceed 200 mg in 24 hours
• May take with or without food
• Report any signs of allergic reaction (rash, swelling, difficulty breathing)
• Inform healthcare provider of all medications being taken
• Not for preventive use - only for acute migraine attacks
• May cause drowsiness - use caution when driving or operating machinery
• Store at room temperature

References

1. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the Acute Treatment of Migraine. N Engl J Med. 2019;381(23):2230-2241. 2. FDA prescribing information: UBRELVY (ubrogepant) tablets. Revised December 2023. 3. Lipton RB, Dodick DW, Ailani J, et al. Effect of Ubrogepant vs Placebo on Pain and the Most Bothersome Associated Symptom in the Acute Treatment of Migraine: The ACHIEVE II Randomized Clinical Trial. JAMA. 2019;322(19):1887-1898. 4. Voss T, Lipton RB, Dodick DW, et al. A phase IIb randomized, double-blind, placebo-controlled trial of ubrogepant for the acute treatment of migraine. Cephalalgia. 2016;36(9):887-898. 5. American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache. 2019;59(1):1-18.