Introduction: There is growing interest in identifying drug interactions between Paxlovid (nirmatrelvir/ritonavir), an antiviral drug used for the management of outpatients with mild to moderate coronavirus disease, and antiepileptic drugs. Methods: We searched the databases PubMed, MEDLINE, Cochrane, and EMBASE from their inception until 30 May 2025, using the keywords "Paxlovid" or "nirmatrelvir/ritonavir" or "antivirals COVID-19" and then "anticonvulsants" and finally "IDDs" and "drug interaction" in combination with Boolean logic operators. Results: Clinical studies have reported strong and important drug-drug interactions between nirmatrelvir/ritonavir and antiepileptic drugs. Interactions with antiepileptic drugs are bidirectional. Moderate or strong CYP3A4 inducers among antiepileptic drugs should be dose-adjusted in patients taking nirmatrelvir/ritonavir. Conclusion: In patients with epilepsy treated with antiepileptic drugs who also use Paxlovid (nirmatrelvir/ritonavir), therapeutic monitoring and intervention on the therapeutic concentration with dose adjustment of the antiepileptic drug is recommended.
Marcianò et al. (Thu,) studied this question.