Introduction
Ubrogepant is an oral calcitonin gene-related peptide (CGRP) receptor antagonist approved for the acute treatment of migraine with or without aura in adults. It represents a novel therapeutic class specifically developed for migraine treatment, offering an alternative to traditional migraine medications such as triptans and ergot derivatives.
Mechanism of Action
Ubrogepant selectively blocks the CGRP receptor, preventing CGRP-mediated vasodilation and neurogenic inflammation. CGRP is a neuropeptide strongly implicated in migraine pathophysiology, with elevated levels during migraine attacks. By antagonizing the CGRP receptor, ubrogepant inhibits the trigeminovascular system activation that underlies migraine pain and associated symptoms.
Indications
- Acute treatment of migraine with aura in adults
- Acute treatment of migraine without aura in adults
Ubrogepant is indicated for use when a migraine attack occurs, not for migraine prevention.
Dosage and Administration
Initial dose: 50 mg or 100 mg orally as a single dose Maximum daily dose: 200 mg (may be taken as two separate doses of 50 mg or 100 mg with at least 2 hours between doses) Special populations:- Hepatic impairment: Avoid use in severe hepatic impairment (Child-Pugh C)
- Renal impairment: No dosage adjustment necessary for mild to moderate impairment; avoid in severe renal impairment (CrCl <30 mL/min)
- Geriatric patients: Use with caution due to increased potential for adverse effects
- Pregnancy: Limited data available; use only if potential benefit justifies potential risk
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with median Tmax of approximately 1.5 hours Distribution: Volume of distribution ~1000 L; protein binding ~87% Metabolism: Primarily metabolized by CYP3A4 with minor contributions from other enzymes Elimination: Half-life ~5-7 hours; primarily excreted in feces (42%) and urine (24%) Food effects: No clinically significant effect on absorptionContraindications
- Hypersensitivity to ubrogepant or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors
- Severe hepatic impairment (Child-Pugh C)
- Severe renal impairment (CrCl <30 mL/min)
Warnings and Precautions
- Hepatotoxicity: Monitor liver enzymes before starting treatment and periodically during therapy
- Hypersensitivity reactions: May occur, including facial swelling and urticaria
- CYP3A4 interactions: Significant drug interaction potential requires careful medication review
- Overuse: May lead to medication-overuse headache; limit use to ≤8 days per month
- Cardiovascular disease: Use with caution in patients with cardiovascular risk factors
Drug Interactions
Major interactions:- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin): Contraindicated due to significant increase in ubrogepant exposure
- Moderate CYP3A4 inhibitors (e.g., fluconazole, verapamil, diltiazem): Reduce ubrogepant dose to 50 mg
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease ubrogepant efficacy
- BCRP inhibitors (e.g., cyclosporine, eltrombopag)
- P-gp inhibitors
Adverse Effects
Common adverse reactions (≥2% and more frequent than placebo):- Nausea (4% vs 2% placebo)
- Somnolence (3% vs 1% placebo)
- Dry mouth (2% vs 1% placebo)
- Hypersensitivity reactions
- Hepatotoxicity
Monitoring Parameters
- Liver function tests (ALT, AST) at baseline and periodically during treatment
- Frequency of migraine attacks and medication use patterns
- Therapeutic response and pain relief
- Adverse effects, particularly gastrointestinal symptoms and sedation
- Signs of hypersensitivity reactions
Patient Education
- Take at the first sign of migraine symptoms
- Do not exceed maximum daily dose of 200 mg
- Do not take with strong CYP3A4 inhibitors (check with pharmacist or provider)
- Report any signs of allergic reaction (swelling, rash, difficulty breathing)
- Monitor liver health and report unusual fatigue, jaundice, or dark urine
- Keep a migraine diary to track frequency and medication use
- Avoid driving or operating machinery if experiencing drowsiness
- Inform healthcare providers of all medications being taken
References
1. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the acute treatment of migraine. N Engl J Med. 2019;381(23):2230-2244. 2. 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. 3. Ubrogepant [package insert]. Madison, NJ: Allergan USA, Inc.; 2023. 4. VanderPluym JH, Halker Singh RB, Urtecho M, et al. Acute treatments for episodic migraine in adults: a systematic review and meta-analysis. JAMA. 2021;325(23):2357-2369. 5. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18.
This monograph is intended for educational purposes only and should not replace professional medical advice. Always consult with a healthcare provider for personalized medical recommendations.