How is Nurtec (rimegepant) dosed and used for acute and preventive treatment of migraine, and what are its safety considerations and alternative options?

Nurtec (Rimegepant) for Migraine: Dosing, Use, and Safety

FDA-Approved Dosing

For acute treatment of migraine, take rimegepant 75 mg orally as needed, with a maximum of one dose (75 mg) in any 24-hour period. 1

For preventive treatment of episodic migraine, take rimegepant 75 mg orally every other day. 1

• The safety of using more than 18 doses in a 30-day period has not been established. 1
• When combining preventive and acute use, the maximum is 18 doses in 30 days. 2
• If you need an acute dose on a non-scheduled preventive day, you may take one 75 mg tablet that day. 3

Administration Instructions

• Use dry hands to peel back the foil covering of one blister. 1
• Do not push the tablet through the foil—gently remove it instead. 1
• Place the orally disintegrating tablet (ODT) 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

For Acute Treatment

Rimegepant is a third-line option for acute migraine, reserved for patients who do not tolerate or have inadequate response to combination therapy of a triptan plus an NSAID. 4, 5

• First-line: Start with NSAIDs (ibuprofen 400-800 mg, naproxen 500-825 mg, or aspirin 1000 mg) or acetaminophen 1000 mg for mild-to-moderate attacks. 5
• Second-line: Add a triptan to the NSAID for moderate-to-severe attacks or when NSAIDs fail after 2-3 episodes. 5
• Third-line: Consider rimegepant (or other gepants like ubrogepant or zavegepant) only after triptan-NSAID combinations fail. 4, 5

For Prevention

Rimegepant is positioned as a preventive option when traditional oral preventives (beta-blockers, topiramate, amitriptyline) have failed or are contraindicated. 4, 2

• The 2025 American College of Physicians guidelines recommend initiating monotherapy with beta-blockers (propranolol 80-240 mg/day or timolol 20-30 mg/day), topiramate, or amitriptyline as first-line preventive agents. 4
• Rimegepant is considered when these first-line agents are not tolerated or result in inadequate response. 4
• The VA/DoD guidelines note insufficient evidence to make a firm recommendation for or against rimegepant for prevention, though they acknowledge its efficacy for acute treatment. 2

Efficacy Evidence

Acute Treatment

• Rimegepant 75 mg produces significant freedom from pain at 2 hours post-dose compared to placebo (p < 0.001). 6
• It also provides significant pain relief (p < 0.001) and freedom from the most bothersome symptom (p < 0.001) at 2 hours. 6

Preventive Treatment

• Rimegepant reduced monthly migraine days by 0.8 days more than placebo (4.3 vs 3.5 days reduction, p = 0.0099) in a phase 2/3 randomized controlled trial. 2, 7
• Over a 52-week open-label extension, there was a mean decrease of 6.2 days in monthly migraine days, with sustained and increasing treatment benefits without diminution of effect. 3
• In a Japanese trial, rimegepant reduced monthly migraine days by 1.1 days more than placebo (p = 0.002). 8

Safety Profile and Adverse Events

Rimegepant was generally well tolerated, with adverse event rates similar to placebo (36% vs 36%). 7

• Most common adverse events include upper respiratory tract infection, nasopharyngitis, sinusitis, constipation, and nausea. 2, 3
• Serious adverse events occurred in only 2.2% of participants over 52 weeks, with none being liver-related. 3
• No participant had ALT or AST > 3× upper limit of normal concurrent with total bilirubin > 2× upper limit of normal. 3
• Only 2.8% discontinued due to adverse events, and only 0.3% discontinued due to liver enzyme-related adverse events. 3
• There is no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials. 9

Contraindications and Drug Interactions

Rimegepant is contraindicated in patients with a history of hypersensitivity reaction to rimegepant or any of its components. 1

• Hypersensitivity reactions, including dyspnea and rash, can occur days after administration. 1
• If a hypersensitivity reaction occurs, discontinue rimegepant immediately and initiate appropriate therapy. 1

Drug Interactions

• Avoid concomitant use with strong CYP3A4 inhibitors. 1
• Avoid another dose within 48 hours when used with moderate CYP3A4 inhibitors. 1
• Avoid concomitant use with strong or moderate CYP3A inducers, which may lead to loss of efficacy. 1
• Avoid another dose within 48 hours when used with potent P-gp inhibitors. 1

Critical Medication-Overuse Prevention

Limit rimegepant use to no more than 8 migraine attacks per 30-day period to prevent medication-overuse headache. 4

• All acute migraine medications should be limited to no more than 2 days per week (10 days per month) to prevent medication-overuse headache. 5
• If you need acute treatment more than twice weekly, initiate preventive therapy immediately. 5
• Medication-overuse headache can paradoxically increase headache frequency and lead to daily headaches. 5

Alternative Options

When Rimegepant Fails or Is Contraindicated

For acute treatment, consider other gepants (ubrogepant 50-100 mg or zavegepant) or lasmiditan (50-200 mg) as alternatives. 4, 5

• Ubrogepant and zavegepant are CGRP antagonists with no vasoconstriction, making them safe for patients with cardiovascular disease. 4
• Lasmiditan is a 5-HT1F receptor agonist without vasoconstrictor activity, but patients must not drive or operate machinery for at least 8 hours after taking it. 10
• Dihydroergotamine (DHE) intranasal or IV has good evidence for efficacy as monotherapy. 5

For preventive treatment, first-line alternatives include propranolol 80-240 mg/day, timolol 20-30 mg/day, topiramate, or amitriptyline 30-150 mg/day. 4

• CGRP monoclonal antibodies (eptinezumab, erenumab, fremanezumab, galcanezumab) are alternatives when oral preventives fail. 4
• OnabotulinumtoxinA is the only FDA-approved preventive therapy specifically for chronic migraine and should be used when three oral preventives have failed. 10

Common Pitfalls to Avoid

• Do not use rimegepant as first-line acute treatment—start with NSAIDs or triptan-NSAID combinations first. 4, 5
• Do not allow patients to increase frequency of acute medication use in response to treatment failure—this creates a vicious cycle of medication-overuse headache. 10
• Do not prescribe opioids or butalbital-containing compounds for migraine, as they lead to dependency, rebound headaches, and loss of efficacy. 5
• Do not delay preventive therapy while trialing multiple acute strategies—if headaches occur more than twice weekly, initiate prevention immediately. 10, 5