Using known drug interactions to manage supratherapeutic calcineurin inhibitor concentrations

To summarize the available body of evidence guiding the management of supratherapeutic concentrations of calcineurin inhibitors (CNI) using cytochrome P450 (CYP450) enzyme inducers.

A nondate restricted literature search within MEDLINE, Embase, and Scopus was performed using the terms "cyclosporine," "tacrolimus," "calcineurin inhibitor," "toxicity," "pharmacokinetics," "carbamazepine," "rifampin," "phenytoin," and "phenobarbital." Additional references were identified from a review of all included citations. All English-language reports that describe the management of supratherapeutic CNI concentrations with interventions targeting metabolic induction using CYP450 enzyme inducers were evaluated.

A total of 10 publications were identified in which a CYP450 enzyme inducer was utilized intentionally to enhance CNI clearance in the setting of supratherapeutic concentrations; 7 case reports describe the use of phenytoin and 3 case reports describe the use of phenobarbital. Patient demographics, dosing strategies employed, and reported efficacy across this series of publications are heterogeneous; however, both agents appear to be well-tolerated when used in this setting.

There is a paucity of published data on the use of CYP450 enzyme inducers for the management of supratherapeutic CNI concentrations. While routine use of this approach cannot be recommended, thorough risk-benefit analyses should be performed in the management of each such clinical scenario.