What is the recommended dosing regimen of Nurtec ODT (rimegepant) for an adult patient for acute migraine treatment and for migraine prevention?

Nurtec ODT (Rimegepant) Dosing for Acute and Preventive Migraine Treatment

For acute migraine treatment, take rimegepant 75 mg orally as a single dose at migraine onset (maximum one dose per 24 hours, up to 18 doses per 30 days); for preventive treatment, take rimegepant 75 mg orally every other day. 1

Acute Treatment Dosing

• The FDA-approved dose is 75 mg taken orally as needed at the onset of migraine with or without aura. 1
• The maximum dose in any 24-hour period is 75 mg (one tablet). 1
• Do not exceed 18 doses in a 30-day period, as safety beyond this frequency has not been established. 1
• Rimegepant demonstrates superiority over placebo for pain freedom at 2 hours (18.2% vs 10.6%) and freedom from most bothersome symptom at 2 hours (48.0% vs 31.8%) in adults. 2
• In patients unsuitable for triptans (due to intolerance, lack of efficacy, or contraindications), rimegepant achieves pain relief at 2 hours in 55.9% versus 32.7% with placebo. 3

Preventive Treatment Dosing

• The FDA-approved preventive dose is 75 mg taken orally every other day for episodic migraine. 1
• This every-other-day regimen reduces monthly migraine days by a mean of 4.4 days during long-term treatment. 4
• Rimegepant receives a "weak for" recommendation from the 2023 VA/DoD guideline for acute treatment, with a number needed to treat of 13 for pain freedom at 2 hours. 5, 6

Administration Instructions

• Use dry hands to peel back the foil covering of one blister; do not push the tablet through the foil. 1
• Place the orally disintegrating tablet on or under the tongue immediately after opening the blister. 1
• The tablet will disintegrate in saliva and can be swallowed without additional liquid. 1
• Do not store the tablet outside the blister pack for future use. 1

Position in Treatment Algorithm

• Rimegepant is recommended as a third-line option after failure of or contraindication to combination therapy with a triptan plus an NSAID. 7
• First-line therapy for mild-to-moderate migraine should be an NSAID (ibuprofen 400–800 mg, naproxen 500–825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg. 7, 6
• If NSAIDs provide inadequate relief, add a triptan (e.g., sumatriptan 50–100 mg) to the NSAID regimen for moderate-to-severe attacks. 7, 6
• Only after failure of triptan-NSAID combinations should CGRP antagonists like rimegepant be considered. 7
• Rimegepant is particularly valuable for patients with cardiovascular contraindications to triptans, as it has no vasoconstrictor activity. 7, 3

Drug Interactions and Dosing Adjustments

• Avoid concomitant use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin). 1
• When co-administered with moderate CYP3A4 inhibitors (e.g., fluconazole, verapamil), avoid another dose of rimegepant within 48 hours. 1
• Avoid concomitant use with strong or moderate CYP3A inducers (e.g., rifampin, phenytoin, carbamazepine), which may lead to loss of efficacy. 1
• When co-administered with potent P-glycoprotein inhibitors (e.g., cyclosporine, quinidine), avoid another dose within 48 hours. 1

Safety and Tolerability

• The incidence of treatment-emergent adverse events is comparable to placebo (15.2% vs 16.4% in Chinese adults; 12.5% vs 12.1% in triptan-unsuitable adults). 3, 2
• Most adverse events are mild or moderate; the most common are upper respiratory tract infection (8.8%), nasopharyngitis (6.8%), and sinusitis (5.1%) during long-term use. 8
• Hypersensitivity reactions (including dyspnea and rash) can occur days after administration; discontinue rimegepant and initiate appropriate therapy if hypersensitivity occurs. 1
• No signal of drug-induced liver injury, medication-overuse headache, or potential drug abuse has been identified in long-term studies. 4, 8
• Rimegepant is contraindicated in patients with a history of hypersensitivity to rimegepant or any of its components. 1

Critical Frequency Limitation to Prevent Medication-Overuse Headache

• Limit all acute migraine medications (including rimegepant) to no more than 2 days per week (≤10 days per month) to prevent medication-overuse headache, which can paradoxically increase headache frequency and lead to daily headaches. 5, 7
• If acute treatment is needed more than twice weekly, initiate preventive therapy immediately rather than increasing the frequency of acute medications. 5, 7
• The FDA label permits up to 18 doses per 30 days for acute treatment, but clinical guidelines emphasize the ≤10 days per month threshold to avoid medication-overuse headache. 1, 5, 7

Long-Term Safety Data

• In a 52-week open-label study of 1800 participants using rimegepant as needed, 84.6% reported at least one treatment-emergent adverse event, but only 19.2% reported events considered rimegepant-related. 8
• No rimegepant-related serious adverse events or events leading to treatment discontinuation were reported in a 52-week Chinese study. 4
• Long-term every-other-day dosing plus as-needed dosing for 12 weeks was safe and well tolerated, with no signal of hepatotoxicity. 8