Introduction
Rimegepant is an orally administered 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 that offers a non-opioid, non-vasoconstrictive approach to migraine management. As the first dual formulation (oral disintegrating tablet and conventional tablet) gepant, it provides flexibility in administration during migraine attacks.
Mechanism of Action
Rimegepant selectively antagonizes the calcitonin gene-related peptide (CGRP) receptor, which plays a crucial role in migraine pathophysiology. CGRP is a neuropeptide released during migraine attacks that causes cranial vasodilation, neurogenic inflammation, and pain transmission. By blocking CGRP binding at its receptor, rimegepant inhibits the neurovascular events underlying migraine without causing vasoconstriction, making it suitable for patients with cardiovascular risk factors.
Indications
- Acute treatment of migraine with or without aura in adults
- Not indicated for the preventive treatment of migraine
Dosage and Administration
Standard dosing: 75 mg orally as a single dose Administration options:- Conventional tablet: Swallow whole with water
- Orally disintegrating tablet: Place on tongue without water
- Hepatic impairment: Contraindicated in severe hepatic impairment (Child-Pugh C)
- Renal impairment: No dosage adjustment needed for mild to moderate impairment; use with caution in severe impairment
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with Tmax of approximately 1.5 hours; bioavailability ~20% Distribution: Volume of distribution ~120 L; protein binding ~96% Metabolism: Primarily metabolized by CYP3A4 with minor contributions from CYP2C9 Elimination: Half-life ~11 hours; primarily excreted in feces (78%) and urine (24%) Food effects: No clinically significant effect on absorptionContraindications
- History of hypersensitivity to rimegepant or any component of the formulation
- Severe hepatic impairment (Child-Pugh Class C)
- Concomitant use with strong CYP3A4 inhibitors
- Concomitant use with strong CYP3A4 inducers
Warnings and Precautions
Hepatotoxicity: Monitor liver enzymes before and during treatment; discontinue if ALT/AST elevations >3× ULN persist Hypersensitivity reactions: Angioedema and urticaria have been reported; discontinue if occurs Cardiovascular events: Although not vasoconstrictive, monitor patients with cardiovascular risk factors Medication overuse headache: May occur with frequent use; limit to ≤10 days per month Pregnancy: No adequate human data; use only if potential benefit justifies potential risk Lactation: Not recommended during breastfeedingDrug Interactions
Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin): Contraindicated due to significant increase in rimegepant exposure Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, St. John's wort): Contraindicated due to significant decrease in rimegepant efficacy Moderate CYP3A4 inhibitors (e.g., fluconazole, diltiazem): Avoid concomitant use P-glycoprotein inhibitors: May increase rimegepant concentrations; monitor for adverse effectsAdverse Effects
Common (≥2%):- Nausea (2%)
- Somnolence (1.5%)
- Dry mouth (1%)
- Hypersensitivity reactions
- Hepatotoxicity
- Severe nausea requiring discontinuation
Monitoring Parameters
- Liver function tests (baseline and periodically during treatment)
- Migraine frequency and characteristics
- Medication use patterns to prevent medication overuse headache
- Signs of hypersensitivity reactions
- Therapeutic response and adverse effects
Patient Education
- Take at the first sign of migraine headache
- Do not exceed one dose every 24 hours
- Do not use more than 10 days per month to prevent medication overuse headache
- Report any signs of allergic reaction (rash, swelling, difficulty breathing)
- Inform healthcare provider of all medications being taken, including OTC products
- Avoid grapefruit juice during treatment
- Store at room temperature; protect orally disintegrating tablets from moisture
- Seek immediate medical attention for chest pain, shortness of breath, or severe abdominal pain
References
1. Croop R, et al. Efficacy, safety, and tolerability of rimegepant orally disintegrating tablet for the acute treatment of migraine: a randomised, phase 3, double-blind, placebo-controlled trial. Lancet. 2019;394(10200):737-745. 2. FDA prescribing information: NURTEC ODT (rimegepant) tablets. Revised 2023. 3. Lipton RB, et al. Rimegepant 75 mg for the acute treatment of migraine: results from a phase 3, double-blind, randomized, placebo-controlled trial. Headache. 2019;59(8):1288-1297. 4. Marcus R, et al. Characterization of the pharmacokinetics and metabolism of rimegepant in healthy participants. Clin Pharmacol Drug Dev. 2021;10(3):270-283. 5. Ailani J, et al. Long-term safety and tolerability of rimegepant 75 mg for the acute treatment of migraine: interim analysis of a 1-year open-label safety study. Cephalalgia. 2021;41(7):701-712.