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.