Drug Interaction Report

MONITOR: Coadministration with conivaptan may increase the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by conivaptan. In pharmacokinetic studies with drugs that are primarily metabolized by CYP450 3A4 such as midazolam, simvastatin, and amlodipine, conivaptan has increased systemic exposure (AUC) by 2- to 3-fold.

MANAGEMENT: Caution is advised if conivaptan must be used concurrently with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever conivaptan is added to or withdrawn from therapy, or the combination avoided altogether. If a clinical decision is made to discontinue concomitant medications at recommended doses, clinicians should allow an appropriate amount of time following the end of conivaptan administration before resuming these medications.