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Study breakdown

Rimegepant Migraine Drug Works Equally Well as Dissolving Tablet Under or On Top of the Tongue

evidence
The takeaway

The orally disintegrating tablet form of the CGRP-blocking migraine drug rimegepant is bioequivalent to the standard oral tablet whether placed under or on top of the tongue.

97-98% AUC equivalence

Both sublingual and supralingual dissolving tablets matched the standard oral tablet's drug absorption within bioequivalence criteria

What the researchers found

Two phase 1 randomized studies in healthy adults demonstrated that rimegepant 75 mg orally disintegrating tablet (ODT) is bioequivalent to the 75 mg oral tablet:

- Sublingual ODT vs. oral tablet: AUC0-t ratio 97%, AUC0-inf ratio 97%, Cmax ratio 105% — all 90% CIs within the 80-125% bioequivalence range

- Supralingual ODT vs. oral tablet: AUC0-t ratio 98%, AUC0-inf ratio 98%, Cmax ratio 103% — all within bioequivalence criteria

Both delivery methods achieved equivalent drug exposure, confirming the ODT formulation provides consistent absorption regardless of whether it's placed under or on top of the tongue.

Why it matters

For migraine patients who may experience nausea or difficulty swallowing during an attack, a dissolving tablet that works without water is a meaningful practical advantage. Confirming bioequivalence ensures patients get the same therapeutic benefit from the more convenient formulation.

How the study worked

Two single-center, phase 1, open-label, randomized bioequivalence studies in healthy adult non-smokers aged 18-55 years. One study compared sublingual ODT to oral tablet; the other compared supralingual ODT to oral tablet. Pharmacokinetic parameters measured included AUC0-t, AUC0-inf, and Cmax, with bioequivalence defined as 90% confidence intervals within the 80-125% range.

What this study cannot tell us

Studies were conducted in healthy volunteers, not migraine patients during attacks. Absorption during a migraine (when gastric motility may be altered) was not assessed. The studies were open-label. Only single doses were evaluated; steady-state bioequivalence for preventive use was not tested.

How to read the evidence

These are well-designed phase 1 randomized bioequivalence studies following standard regulatory methodology. The evidence is strong for pharmacokinetic equivalence but was conducted in healthy volunteers, not patients.

When this study was published

Published in 2024, this study supports the currently marketed rimegepant ODT formulation, which is one of the newer CGRP-targeting migraine treatments available.

The bigger picture

CGRP-targeting drugs have transformed migraine treatment since their introduction. Rimegepant's ODT formulation represents the practical refinement phase of this peptide-based therapeutic class — making established treatments more convenient and accessible while maintaining the same efficacy profile.

Questions still open

  • Does the ODT formulation absorb equally well during an active migraine when nausea is present?
  • Do patients prefer the dissolving tablet over the standard oral tablet in real-world use?
  • Is there a speed-of-onset difference between formulations that might matter for acute migraine treatment?

Common questions

What is CGRP and how does rimegepant work against migraines?
CGRP (calcitonin gene-related peptide) is a peptide released during migraines that causes blood vessels in the brain to dilate and triggers pain and inflammation. Rimegepant blocks the CGRP receptor, preventing these effects. It can both treat active migraines and prevent future attacks when taken regularly.
Does it matter where I put the dissolving rimegepant tablet in my mouth?
No — this study confirmed that the dissolving tablet works equally well whether placed under the tongue (sublingual) or on top of it (supralingual). Both deliver the same amount of medication as swallowing a standard tablet, so you can use whichever placement is most comfortable.

Read the original research

Bioequivalence of rimegepant, a small molecule CGRP receptor antagonist, administered as an oral tablet, a sublingual orally disintegrating tablet, and a supralingual orally disintegrating tablet: two phase 1 randomized studies in healthy adults.

Cephalalgia : an international journal of headache, 44(2), 3331024231219505

Citation

Croop, Robert; Bhardwaj, Rajinder; Anderson, Matt S; Matschke, Kyle T; Hould, Jennifer; Bertz, Richard; Liu, Jing; Lipton, Richard B. (2024). Bioequivalence of rimegepant, a small molecule CGRP receptor antagonist, administered as an oral tablet, a sublingual orally disintegrating tablet, and a supralingual orally disintegrating tablet: two phase 1 randomized studies in healthy adults.. Cephalalgia : an international journal of headache, 44(2), 3331024231219505. https://doi.org/10.1177/03331024231219505