COVID-19 and antiepileptic drugs: an approach to guide practices when nirmatrelvir/ritonavir is co-prescribed

Eur J Clin Pharmacol. 2022 Oct;78(10):1697-1701. doi: 10.1007/s00228-022-03370-7. Epub 2022 Aug 5.

Abstract

Management and dose adjustment are a major concern for clinicians in the absence of specific clinical outcome data for patients on antiepileptic drugs (AEDs), in the event of short-term (5 days) nirmatrelvir/ritonavir co-exposure. Therefore, in this report, we identified drugs that require dose adjustment because of drug-drug interactions (DDIs) between nirmatrelvir/ritonavir and AEDs. We hereby used four databases (Micromedex Drug Interaction, Liverpool Drug Interaction Group for COVID-19 Therapies, Medscape Drug Interaction Checker, and Lexicomp Drug Interactions) and DDI-Predictor.In the light of applying the DDI-Predictor, for carbamazepine, clobazam, oxcarbazepine, eslicarbazepine, phenytoin, phenobarbital, pentobarbital, rufinamide, and valproate as CYP3A4 inducers, we recommend that a dose adjustment of short-term nirmatrelvir/ritonavir as a substrate (victim) drug would be more appropriate instead of these AEDs to avoid impending DDI-related threats in patients with epilepsy.

Keywords: Anticonvulsants; Dosing; Drug interaction; Nirmatrelvir; Ritonavir; SARS-CoV-2; Seizure.

Publication types

  • Review

MeSH terms

  • Anticonvulsants* / therapeutic use
  • COVID-19 Drug Treatment*
  • Carbamazepine / therapeutic use
  • Clobazam
  • Cytochrome P-450 CYP3A Inducers
  • Drug Interactions
  • Humans
  • Oxcarbazepine
  • Pentobarbital
  • Phenobarbital
  • Phenytoin
  • Ritonavir / therapeutic use
  • Valproic Acid / therapeutic use

Substances

  • Anticonvulsants
  • Cytochrome P-450 CYP3A Inducers
  • Clobazam
  • Carbamazepine
  • Valproic Acid
  • Phenytoin
  • Pentobarbital
  • Ritonavir
  • Oxcarbazepine
  • Phenobarbital