Coadministration has not been studied and is contraindicated. Phenytoin is mainly metabolised by CYP2C9 and to a lesser extent by CYP2C19. Doravirine is metabolized by CYP3A4. Lamivudine and tenofovir-DF are eliminated renally. Doravirine is unlikely to affect phenytoin metabolism. No interaction is expected with lamivudine. Phenytoin is an inducer of P-gp and may reduce the absorption of tenofovir-DF. However, based on the results of the interaction study between tenofovir-DF and rifampicin (another inducer of P-gp), phenytoin would only be expected to cause a small decrease in tenofovir-DF. However, phenytoin is a strong inducer of CYP3A4 and is expected to substantially decrease doravirine exposure which may result in loss of therapeutic effect and development of resistance. Alternative anticonvulsants should be considered. At least a 4-week cessation period is recommended prior to initiation of doravirine due to the persisting inducing effect upon discontinuation of a moderate/strong inducer.