Rimegepant (Nurtec ODT) Is Not Indicated for Non-Migraine Headaches
Rimegepant is FDA-approved exclusively for migraine with or without aura and has no evidence supporting its use for tension-type, sinus, or medication-overuse headaches. 1
Evidence Base and Mechanism of Action
Rimegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist that specifically targets the pathophysiology of migraine attacks. 1 The drug's mechanism—blocking CGRP receptors—addresses the neurogenic inflammation and vasodilation unique to migraine, not the muscle tension or other mechanisms underlying non-migraine headache types. 2
All pivotal phase III trials enrolled only patients with confirmed migraine diagnoses (with or without aura), demonstrating efficacy specifically for pain freedom and most bothersome migraine symptom relief at 2 hours post-dose. 1, 3, 4 No studies have evaluated rimegepant for tension-type headache, sinus headache, or any other primary or secondary headache disorder.
Guideline Recommendations for Non-Migraine Headaches
For tension-type headache, the 2024 VA/DoD guidelines recommend ibuprofen 400 mg or acetaminophen 1000 mg as first-line acute treatment. 5 Amitriptyline is suggested for prevention of chronic tension-type headache. 5
For medication-overuse headache (which can develop from frequent triptan or analgesic use), there is insufficient evidence to recommend any specific preventive agent beyond withdrawal of the overused medication. 5 Rimegepant is not studied or recommended for this indication.
Sinus headache is not addressed in migraine treatment guidelines because true sinus headache (from acute sinusitis) requires treatment of the underlying infection, not migraine-specific therapy. 5 Many patients diagnosed with "sinus headache" actually have migraine, which can present with facial pressure and nasal congestion. 5
Critical Clinical Pitfall
Using rimegepant for non-migraine headaches represents off-label use without supporting evidence and exposes patients to unnecessary cost (gepants are expensive compared to first-line analgesics) and potential adverse effects without proven benefit. 5, 2
If a patient with presumed "non-migraine headache" responds to rimegepant, the diagnosis should be reconsidered—they likely have migraine that was initially misclassified. 5 Migraine frequently presents atypically without classic aura, throbbing, or unilateral location, and can be mistaken for tension-type or sinus headache. 5
Appropriate Use of Rimegepant
Rimegepant should be reserved for confirmed migraine in adults, either as acute treatment (75 mg as needed, limited to ≤2 days per week to prevent medication-overuse headache) or as preventive therapy (75 mg every other day for episodic migraine). 1, 6, 5 It represents a valuable option when triptans are contraindicated, ineffective, or poorly tolerated. 4, 2
For non-migraine headaches, use evidence-based first-line treatments: NSAIDs or acetaminophen for tension-type headache, and appropriate management of underlying causes for secondary headaches. 5