How is Remgepant (Gepant) used for migraine prophylaxis?

How to Use Rimegepant for Migraine Prophylaxis

Rimegepant 75 mg should be taken orally every other day for the preventive treatment of episodic migraine in adults, with efficacy assessed after 3-6 months of treatment. 1, 2

Dosing and Administration

• Take rimegepant 75 mg orally disintegrating tablet every other day (not daily) for migraine prevention 3, 4
• The orally disintegrating tablet formulation offers convenience and does not require water for administration 5
• Continue treatment for at least 3-6 months before assessing efficacy—do not abandon treatment prematurely 1, 2
• Patients may use acute migraine treatments (triptans, NSAIDs, acetaminophen, antiemetics) as needed while on preventive therapy 3

Patient Selection Criteria

Rimegepant is positioned as a second-line preventive option when first-line treatments fail, are not tolerated, or provide inadequate response 6, 2

• Consider rimegepant for patients adversely affected by migraine on ≥2 days per month despite optimized acute treatment 2
• Appropriate for patients who have failed or cannot tolerate first-line preventive medications (beta-blockers, topiramate, candesartan) 2
• The 2023 VA/DoD guideline gives rimegepant a "neither for nor against" recommendation for episodic migraine prevention, noting that the 0.8-day reduction in monthly migraine days was statistically but not clinically significant by their threshold 1
• Rimegepant is approved specifically for episodic migraine prevention (not chronic migraine) in patients averaging approximately 10 monthly migraine days 3, 4

Expected Efficacy Outcomes

• Primary outcome: Reduction of approximately 0.8 monthly migraine days compared to placebo during weeks 9-12 of treatment 1, 3
• Secondary outcome: Approximately 49% of patients achieve ≥50% reduction in moderate-to-severe monthly migraine days (versus 41.5% with placebo) 3
• The mean reduction from baseline is approximately 4.3 monthly migraine days with rimegepant versus 3.5 days with placebo 3, 4
• Benefits are maintained over longer-term use (up to 52 weeks) 5

Safety and Tolerability Profile

• Rimegepant has a favorable safety profile with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials 5
• Most common adverse events include nasopharyngitis, nausea, and upper respiratory tract infection, occurring at rates similar to placebo 3, 4
• Approximately 36% of patients report adverse events (identical to placebo rate) 4
• Only 2% discontinue due to adverse events 4
• Unlike erenumab, rimegepant has not been associated with development or worsening of hypertension in post-marketing surveillance 6

Concomitant Use with Other CGRP Therapies

• Rimegepant can be safely used for acute treatment in patients already taking CGRP monoclonal antibodies for prevention 7
• No safety issues were identified when rimegepant was combined with erenumab, fremanezumab, or galcanezumab 7
• This allows for dual CGRP pathway targeting: preventive therapy with rimegepant every other day plus acute treatment with rimegepant 75 mg as needed (up to once daily) on migraine days 3, 7

Treatment Duration and Discontinuation

• Consider pausing preventive treatment after 6-12 months of successful therapy to assess whether continued prevention is necessary 1, 2
• This minimizes unnecessary drug exposure and allows some patients to manage migraine with acute medications only 1
• Treatment success is measured by percentage reduction in monthly migraine days or monthly headache days of moderate-to-severe intensity 2

Cost Considerations

• Rimegepant is substantially more expensive than traditional preventive medications, with annual costs ranging from $7,071 to $22,790 6
• Gepants may have low value compared to no preventive treatment based on cost-effectiveness analyses 6
• This cost factor should be weighed against the favorable tolerability profile and convenience of oral administration 6

Common Pitfalls to Avoid

• Do not assess efficacy before 3-6 months of treatment—premature discontinuation is a common error 1, 2
• Do not use rimegepant for chronic migraine prevention, as it is only approved for episodic migraine 3
• Do not prescribe during pregnancy due to limited safety data 2
• Do not expect dramatic reductions in migraine frequency—the clinical benefit is modest (approximately 1 fewer migraine day per month versus placebo) 1
• Do not use concomitantly with other CGRP pathway medications for prevention (though acute use is safe) 3