Drug Interaction Report

MONITOR: Coadministration with miconazole may increase the plasma concentrations of drugs that are substrates of CYP450 3A4. The mechanism is decreased clearance due to inhibition of CYP450 3A4 activity by miconazole, which is thought to be a relatively potent inhibitor of the isoenzyme. No formal drug interaction studies have been conducted with miconazole buccal tablets. Although systemic absorption following mucous membrane exposure is limited, the potential for interaction with drugs metabolized by CYP450 3A4 cannot be ruled out.

MANAGEMENT: Caution is advised if miconazole 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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever miconazole is added to or withdrawn from therapy.

MONITOR: Grapefruit juice may increase the plasma concentrations of tofacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, some authorities recommend avoiding consumption of grapefruit juice during tofacitinib therapy (Canada). Patients receiving tofacitinib therapy who ingest grapefruits or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.