Increasing the dose of voriconazole compensates for enzyme induction by phenytoin

Abstract

We read with interest the manuscript by Dr Alffenaar, in which it was stated that doubling the dose of voriconazole does not compensate for induction by phenytoin [1]. Voriconazole, used as first-line agent to treat invasive aspergillosis in immunocompromised patients, is known to have complex pharmacokinetics resulting in variable plasma concentrations [2]. It is recommended to monitor voriconazole plasma concentrations in non-responsive patients, gastro-intestinal dysfunction, severe hepatopathy, unexplained neurological symptoms and in children. Target concentrations should be higher than 1 or 2 mg l−1 to guarantee efficacy and lower than 6 mg l−1 to avoid toxicity [2]. Also, co-administration of other drugs can result in fluctuating plasma concentrations as voriconazole is metabolized by CYP2C9, CYP2C19 and to a lesser extent by CYP3A4. Plasma concentrations are drastically lowered by CYP450 inducers including rifampicin, phenobarbital and carbamazepine. Consequently, concomitant use of these drugs is contra-indicated [3].