Drug Interaction Report

MONITOR: Danazol may increase carbamazepine levels by inhibiting the CYP450 3A4 hepatic metabolism of carbamazepine. Carbamazepine toxicity is possible.

MANAGEMENT: If these drugs must be used together, close observation for clinical and laboratory evidence of carbamazepine toxicity is recommended. Patients should be advised to report possible signs of carbamazepine toxicity (nausea, visual disturbances, dizziness, or ataxia). Dose adjustments may be required.

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.