Rimegepant Drug Interactions
Avoid rimegepant with strong CYP3A4 inhibitors, strong or moderate CYP3A4 inducers, and use caution with moderate CYP3A4 inhibitors and potent P-glycoprotein inhibitors by extending the dosing interval to at least 48 hours. 1
Strong CYP3A4 Inhibitors (Contraindicated)
Avoid concomitant administration entirely with the following strong CYP3A4 inhibitors, as they increase rimegepant exposure by over 4-fold 1, 2:
- Itraconazole - increases rimegepant AUC by 4.14-fold and Cmax by 1.42-fold 2
- Ketoconazole 1
- Clarithromycin 1
The magnitude of this interaction is clinically significant and can lead to excessive drug exposure and potential adverse effects 2.
Moderate CYP3A4 Inhibitors (Dose Adjustment Required)
Avoid another dose of rimegepant within 48 hours when co-administered with moderate CYP3A4 inhibitors 1:
- Fluconazole - increases rimegepant AUC by 1.80-fold without affecting Cmax 2
- Erythromycin 1
- Verapamil 1
These agents cause moderate increases in rimegepant exposure that require extended dosing intervals rather than complete avoidance 2.
Strong or Moderate CYP3A4 Inducers (Contraindicated)
Avoid concomitant administration with strong or moderate CYP3A4 inducers, as they significantly reduce rimegepant exposure and may lead to loss of efficacy 1:
- Rifampin - decreases rimegepant AUC to 19% and Cmax to 36% of normal levels 2
- Carbamazepine 1
- Phenytoin 1
- St. John's Wort 1
The reduction in rimegepant levels is substantial enough to render the medication ineffective 2.
Potent P-glycoprotein Inhibitors (Dose Adjustment Required)
Avoid another dose of rimegepant within 48 hours when co-administered with potent P-gp inhibitors 1:
These medications may increase rimegepant exposure through inhibition of P-glycoprotein-mediated transport 1.
CYP2C9 Interactions (Not Clinically Significant)
CYP2C9 does not play a meaningful role in rimegepant metabolism, despite theoretical concerns 2. Fluconazole, a strong CYP2C9 inhibitor, only modestly increased rimegepant exposure through its moderate CYP3A4 inhibition 2.
CGRP Monoclonal Antibodies (Safe Combination)
Rimegepant can be safely used for acute treatment in patients receiving CGRP monoclonal antibodies for prevention 3:
- Erenumab, fremanezumab, or galcanezumab - no safety concerns identified when used concomitantly with rimegepant 3
- In a study of 13 patients using rimegepant with CGRP mAbs, only 38% reported any adverse events, with no serious events or discontinuations 3
- Mean exposure was 7.8 doses over 4 weeks with good tolerability 3
Clinical Pitfalls to Avoid
Do not assume rimegepant is a CYP3A4 inhibitor requiring dose adjustments of other medications - while rimegepant increased midazolam exposure by 1.86-1.91-fold, this does not represent clinically meaningful CYP3A4 inhibition at therapeutic doses 2.
Do not use rimegepant as preventive therapy without considering the evidence quality - the VA/DoD guidelines state there is insufficient evidence to recommend for or against rimegepant for prevention of episodic migraine, giving it only a "neither for nor against" recommendation 4.
Always check for azole antifungals, macrolide antibiotics, and anticonvulsants before prescribing rimegepant, as these are the most commonly encountered interacting medications in clinical practice 1, 2.