PHENYTOIN AND PROTEASE INHIBITORS

Nelfinavir, fosamprenavir/ritonavir, and lopinavir/ritonavir modestly reduced pheny- toin levels in pharmacokinetic studies. In case reports, ritonavir has decreased, increased or not altered phenytoin levels. Phenytoin decreased lopinavir levels, and possibly also indinavir and ritonavir levels, had only had a minor effect on the levels of amprenavir (given as fosamprenavir/ritonavir), but did not alter nelfinavir levels. Phenytoin is predicted to decrease darunavir and saquinavir levels.
Phenytoin should be used with caution in combination with any protease inhibitor, with close monitoring of antiviral efficacy and phenytoin levels. Consider using an alternative antiepileptic where possible. Note that fospheny- toin, a prodrug of phenytoin, may interact similarly.