Drug Interaction Report

Theoretically, coadministration of dapsone with inducers of CYP450 3A4 such as rifamycins, anticonvulsants, barbiturates, and St. John's wort may increase the formation of dapsone hydroxylamine, a metabolite associated with hemolysis. Dose-related hemolysis is the most common adverse event associated with oral dapsone in both patients with or without glucose-6-phosphate dehydrogenase (G6PD) deficiency. While clinical studies have not demonstrated evidence of clinically significant anemia in patients treated with dapsone 5% gel for acne vulgaris, an increased reticulocyte count and a decreased hemoglobin level were noted to be associated in a G6PD-deficient patient. Exposure to dapsone from the recommended topical dose is about 1% of that from a 100 mg oral dose.

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.