By William Elliott, MD, FACP, and James Chan, PharmD, PhD

Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.

Drs. Elliott and Chan report no financial relationships relevant to this field of study.

The Food and Drug Administration has approved the second oral, non-peptide, small molecule, calcitonin gene-related peptide (CGRP) receptor antagonist, following ubrogepant, for acute migraine. Rimegepant is the first quick-dissolving tablet approved for this indication. It received a priority review and is marketed as Nurtec ODT.

INDICATIONS

Rimegepant should be prescribed to treat acute migraine with or without aura in adults.1

DOSAGE

The recommended dose is 75 mg placed on or under the tongue as needed.1 No water is needed. The maximum dose is one tablet in a 24-hour period. The safety of treating more than 15 migraines that occur in a 30-day period has not been established.1 Rimegepant is available as 75 mg orally disintegrating tablets (ODT).

POTENTIAL ADVANTAGES

Rimegepant is a quick-dissolving tablet that does not require water for administration. It may onset faster vs. ubrogepant. Rimegepant also has a long elimination half-life (approximately 11 hours) vs. five to seven hours for ubrogepant.1,2 This may contribute to a longer duration of action.

POTENTIAL DISADVANTAGES

Rimegepant is a substrate of CYP3A4 as well as transporters P-gp and breast cancer-resistant protein (BCRP); thus, avoid using with strong CYP3A4 inhibitors, strong and moderate CYP3A4 inducers, and inhibitors of P-gp or BCRP.1

COMMENTS

The efficacy of rimegepant was evaluated in a randomized, double-blind, placebo-controlled trial.1,3 Adult subjects with at least a one-year history of migraine, with or without aura, were randomized to rimegepant 75 mg (n = 732) or placebo (n = 734). Subjects were instructed to treat a migraine of moderate to severe headache pain intensity. The coprimary endpoints were percent with freedom from pain and freedom from the most bothersome symptoms (MBS), such as nausea, phonophobia, or photophobia, at two hours postdose. Pain relief was defined as a reduction in migraine pain from moderate or severe severity to mild or none.

Percent responders pain free at two hours were 21.2% for rimegepant vs. 10.9% for placebo. Response for MBS was 35.1% vs. 26.8%, respectively. A series of secondary endpoints included assessed onset of action and durability of effect.2 A higher proportion showed the ability to function normally at 60 minutes postdose (22.3% vs. 15.8%), pain relief at 90 minutes (49.6% vs. 37.2%), sustained pain relief two to 24 hours (47.8% vs. 27.7%), sustained pain relief two to 48 hours postdose (42.2% vs. 25.2%), and use of rescue medication within 24 hours (14.2% vs. 29.2%). Rimegepant appears to be well tolerated. Common adverse events related to treatment were 7% vs. 5% for placebo. These include nausea, urinary tract infection, and dizziness. The most common adverse reaction reported in a long-term, open-label study (n = 1,798) with up to one year of intermittent use was nausea (2% vs. 0.4% for placebo).1

CLINICAL IMPLICATIONS

The American Headache Society recommends triptans, ergotamine derivatives, and nonsteroidal anti-inflammatory drugs (NSAIDs) to treat acute migraines.4 Triptans are first-line treatment, but they are not suitable for patients with vascular risk factors (e.g., ischemic or vasospastic coronary artery disease). In addition, effectiveness and tolerability vary between triptans and individual patients.5 So far, cardiovascular (CV) adverse events have not emerged in clinical trials of rimegepant or ubrogepant, and specific warnings are not part of the current prescribing information. However, patients with CV contraindications were not included in the clinical trials. There are no comparative studies comparing the two oral CGRP inhibitors. Comparing the respective placebo-control studies, the coprimary endpoint responses at two hours postdose appear similar, but the relative time courses of response suggested rimegepant may onset faster and possibly last longer.1-3 Other recent approvals include lasmiditan (a serotonin 1F receptor agonist), ubrogepant, and now rimegepant, all of which may be options for patients who have contraindications to triptans or who have failed to respond to or are intolerant of oral triptans (although these subgroups have not been studied). A recently released report by the Institute for Clinical and Economic Review concluded these three new therapies appear to be less effective overall than triptans.6 They are significantly more expensive, particularly compared to generic triptans. The cost of rimegepant is expected to be $850 per eight-tablet pack, or just over $100 per tablet.

REFERENCES

  1. Biohaven Pharmaceuticals. Nurtec ODT Prescribing Information, February 2020. Accessed March 25, 2020.
  2. Allergan USA, Inc. Ubrelvy Prescribing Information, December 2019. Accessed March 25, 2020.
  3. 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;394:737-745.
  4. American Headache Society. The American Headache Society position statement on integrating new migraine treatments into clinical practice. Headache 2019;59:1-18.
  5. Viana M, Genazzani AA, Terrazzino S, et al. Triptan nonresponders: Do they exist and who are they? Cephalagia 2013;33:891-896.
  6. Institute for Clinical and Economic Review. ICER releases evidence report on acute treatments for migraine, Jan. 10, 2020. Accessed March 25, 2020.