How does Nurtec (rimegepant) work in the body to prevent migraines?

How Nurtec (Rimegepant) Works in the Body to Prevent Migraine

Nurtec (rimegepant) works by blocking calcitonin gene-related peptide (CGRP) receptors, which prevents CGRP from binding to these receptors and inhibits the pain and inflammatory processes involved in migraine pathophysiology. 1

Mechanism of Action

Rimegepant belongs to a class of medications called gepants, which are CGRP receptor antagonists. Here's how it works:

1. CGRP Receptor Blockade:

   • Rimegepant specifically targets and blocks the CGRP receptor binding site 1
   • This prevents CGRP (a protein that contributes to trigeminal nerve pain and inflammation) from binding to its receptor 1

2. Trigeminal System Effects:

   • By blocking CGRP receptors, rimegepant inhibits the transmission of pain signals from trigeminal nerve cells 1
   • This reduces the neurogenic inflammation that occurs during migraine attacks

3. Dual Action:

   • Unlike some migraine medications that only work for acute treatment or prevention, rimegepant is approved for both purposes 2
   • For prevention, it's taken every other day to maintain CGRP receptor blockade 3

Clinical Effects on Migraine Prevention

When used preventively, rimegepant:

• Reduces the mean number of monthly migraine days (MMDs) by approximately 0.8 days compared to placebo 3
• Helps approximately 49.1% of patients achieve at least a 50% reduction in moderate to severe monthly migraine days (compared to 41.5% with placebo) 3
• Maintains its beneficial effects on reducing migraine frequency and improving quality of life over the longer term (up to 52 weeks) 2

Pharmacokinetic Considerations

• Rimegepant is available as an orally disintegrating tablet (ODT), which offers convenience and potentially faster response time 2
• The medication is metabolized primarily by the liver, with increased exposure in patients with severe hepatic impairment 4
• For preventive treatment, the recommended dosing is 75 mg every other day 3

Comparison to Other Migraine Prevention Medications

Rimegepant differs from other migraine preventive medications in several ways:

• Unlike triptans (which bind to 5-HT1B and 5-HT1D receptors), gepants like rimegepant block the CGRP receptor binding site 1
• Unlike CGRP monoclonal antibodies (which either block the peptide from binding to the receptor or block the receptor binding site), gepants are small molecules that can be taken orally 1
• The 2023 VA/DoD headache guideline gives rimegepant a "neither for nor against" recommendation for episodic migraine prevention, noting that it resulted in a statistically significant but not clinically significant reduction in monthly migraine days (0.8 days) 1

Safety Profile

• Rimegepant is generally well tolerated with no evidence of hepatotoxicity or cardiovascular toxicity in clinical trials 2
• Common adverse effects include nausea, urinary tract infection, and dizziness 5
• The safety profile is similar to placebo when used for preventive treatment 6

Important Considerations

• Rimegepant should not be used in patients with severe hepatic impairment due to significantly increased drug exposure (3.9-fold increase in unbound concentrations) 4
• It represents a novel mechanism for migraine prevention compared to traditional preventive medications like beta-blockers, antiseizure medications, or antidepressants 1
• As the first dual agent approved for both treatment and prevention of migraine, rimegepant offers a unique approach to migraine management 2

By targeting the CGRP pathway that is fundamental to migraine pathophysiology, Nurtec provides a mechanism-based approach to preventing migraine attacks through continuous receptor blockade when taken on a regular preventive schedule.