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].
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