Drug Interaction Report

MONITOR: Coadministration with miconazole 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 miconazole. A case of carbamazepine (a CYP450 3A4 substrate) toxicity was reported in a patient shortly after the addition of oral miconazole. Symptoms resolved upon withdrawal of miconazole and reappeared upon rechallenge. Other drugs metabolized by CYP450 3A4 may also be affected.

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as well as clinical and laboratory monitoring may be appropriate for some drugs whenever miconazole is added to or withdrawn from therapy.

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of carbamazepine. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

In a small, randomized, crossover study, the administration of carbamazepine with grapefruit juice (compared to water) increased plasma drug concentrations by approximately 40%. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.

MANAGEMENT: Patients receiving carbamazepine should be advised to avoid or limit consumption of alcohol. Given the drug's narrow therapeutic index, patients receiving carbamazepine therapy should preferably avoid the regular consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels. Patients should be advised to report signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia) to their physicians.