Drug Interaction Report

GENERALLY AVOID: Coadministration with drugs that are capable of increasing the activity of delta-aminolevulinic acid synthetase (e.g., estrogens, barbiturates, steroid metabolites, rifampin) may negate the pharmacologic effect of hemin. In the treatment of porphyria, hemin is thought to limit the rate of porphyrin/heme biosynthesis by inhibiting delta-aminolevulinic acid synthetase, thus any induction of this enzyme would be expected to counteract the therapeutic effect of hemin.

MANAGEMENT: Drugs capable of increasing the activity of delta-aminolevulinic acid synthetase should be avoided during hemin 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.