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should be monitored and the diclofenac dosage adjusted as necessary whenever a CYP450 2C9 inducer is added to or withdrawn from therapy.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailabilities of both elvitegravir and tenofovir. When a single dose of cobicistat/elvitegravir/emtricitabine/tenofovir (trade name Stribild) was given with a light meal (approximately 373 kcal; 20% fat), mean elvitegravir and tenofovir systemic exposures (AUCs) increased by 34% and 24%, respectively, relative to fasting conditions. When administered with a high-fat meal (approximately 800 kcal; 50% fat), the mean AUC of elvitegravir and tenofovir increased by 87% and 23%, respectively, relative to fasting conditions. The alterations in mean AUCs of cobicistat and emtricitabine were not clinically significant with either the light or high-fat meal.

MANAGEMENT: Cobicistat/elvitegravir/emtricitabine/tenofovir as a fixed-dose preparation should be administered once daily with food. Elvitegravir as a single-ingredient preparation should also be administered once daily with food.

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.