Drug Interaction Report

MONITOR: Coadministration with CYP450 2C9 inducers, such as rifampin, may decrease the plasma concentrations and therapeutic effects of diclofenac. The proposed mechanism is rifampin-mediated induction of CYP450 2C9, the isoenzyme responsible for the metabolic clearance of diclofenac. In a study involving 6 healthy subjects, after receiving rifampin 450 mg daily for 6 days, the Cmax and AUC of a single 100 mg dose of diclofenac was reduced by 43% and 67%, respectively.

MANAGEMENT: The potential for diminished pharmacologic effects of diclofenac should be considered during coadministration with CYP450 2C9 inducers, such as rifampin. Pharmacologic response to diclofenac should be monitored and the diclofenac dosage adjusted as necessary whenever a CYP450 2C9 inducer is added to or withdrawn from therapy.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.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.