Introduction
Nurtec ODT (rimegepant) is an orally disintegrating tablet developed by Biohaven Pharmaceuticals for the acute treatment and preventive treatment of migraine in adults. It belongs to the calcitonin gene-related peptide (CGRP) receptor antagonist class, representing a novel approach to migraine therapy that differs from traditional triptans and ergot derivatives.
Mechanism of Action
Rimegepant is a selective and potent antagonist of the calcitonin gene-related peptide (CGRP) receptor. CGRP is a neuropeptide released from trigeminal nerves during migraine attacks that causes vasodilation and neurogenic inflammation. By blocking CGRP receptors, rimegepant inhibits the neurovascular events underlying migraine pathophysiology without causing vasoconstriction, making it suitable for patients with cardiovascular risk factors.
Indications
- Acute treatment of migraine with or without aura in adults
- Preventive treatment of episodic migraine in adults (taken every other day)
Dosage and Administration
Standard dosing: 75 mg orally as a single dose Administration: Place tablet on tongue, where it disintegrates within seconds without need for water Maximum frequency: Do not exceed 1 dose in 24 hours Special populations:- Hepatic impairment: Not recommended in severe impairment (Child-Pugh C)
- Renal impairment: No dosage adjustment needed in mild to moderate impairment; not studied in severe impairment
- Geriatric: No dosage adjustment necessary
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with Tmax of approximately 1.5 hours; bioavailability ~64% Distribution: Volume of distribution ~120 L; protein binding ~96% Metabolism: Primarily via CYP3A4 with minor contributions from CYP2C9 Elimination: Half-life ~11 hours; primarily fecal excretion (78%) with renal elimination (24%)Contraindications
- Hypersensitivity to rimegepant or any component of the formulation
- Concomitant use with strong CYP3A4 inhibitors
- Concomitant use with strong CYP3A inducers
Warnings and Precautions
- Hypersensitivity reactions: Including dyspnea and rash reported in clinical trials
- Hepatic impairment: Use not recommended in severe hepatic impairment
- Pregnancy: No adequate human data; use only if potential benefit justifies potential risk
- Lactation: Not known if excreted in human milk; consider developmental and health benefits versus potential risk
- Geriatric use: No overall differences in safety or effectiveness observed
Drug Interactions
Significant interactions:- Strong CYP3A4 inhibitors (ketoconazole, itraconazole, clarithromycin): Increase rimegepant exposure; contraindicated
- Strong CYP3A inducers (rifampin, carbamazepine, St. John's wort): Decrease rimegepant exposure; contraindicated
- Moderate CYP3A4 inhibitors (erythromycin, verapamil, diltiazem): Avoid concomitant use
- BCRP inhibitors: May increase rimegepant absorption
Adverse Effects
Most common (≥2% and more frequent than placebo):- Nausea (2% vs 0.8% placebo)
- Upper abdominal pain (1% vs 0.4% placebo)
- Dizziness (1% vs 0.8% placebo)
- Somnolence (1% vs 0.6% placebo)
- Hypersensitivity reactions
- Elevated liver enzymes (monitor periodically)
Monitoring Parameters
- Efficacy: Reduction in migraine frequency, severity, and duration
- Safety: Signs of hypersensitivity reactions
- Hepatic function: Consider periodic monitoring in long-term use
- Medication overuse: Monitor for development of medication overuse headache
Patient Education
- Take at the first sign of migraine symptoms
- Tablet dissolves quickly on tongue without water
- Do not exceed one tablet every 24 hours
- Report any signs of allergic reaction (rash, difficulty breathing)
- Inform healthcare provider of all medications being taken
- Not intended for use in cluster headache
- Store at room temperature (20-25°C) in original packaging
References
1. Croop R, Goadsby PJ, Stock DA, 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. Lipton RB, Croop R, Stock EG, et al. Rimegepant, an oral calcitonin gene-related peptide receptor antagonist, for migraine. N Engl J Med. 2019;381(2):142-149. 3. Nurtec ODT [package insert]. Biohaven Pharmaceuticals, Inc.; 2021. 4. Dodick DW, Lipton RB, Ailani J, et al. Ubrogepant for the acute treatment of migraine: pooled efficacy, safety, and tolerability from the ACHIEVE I and ACHIEVE II phase 3 randomized trials. Neurol Ther. 2021;10(1):235-249. 5. FDA-approved labeling: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212728s003lbl.pdf 6. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache. 2019;59(1):1-18.