Drug Interactions between diflunisal and sulindac

GENERALLY AVOID: Concomitant use of more than one nonsteroidal anti-inflammatory drug (NSAID) at a time may increase the potential for serious gastrointestinal toxicity including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, or intestines. These events can occur at any time during NSAID use, with or without warning symptoms. The risk is dependent on both dosage and duration of therapy. Patients with a prior history of peptic ulcer disease and/or GI bleeding have a greater than 10-fold increased risk of developing a GI bleed during NSAID use compared to patients without a history. Additional risk factors include old age, alcohol use, smoking, and poor general health status.

Coadministration of diflunisal with sulindac may result in a reduction in the therapeutic effects of sulindac. The mechanism for this interaction has not been delineated. In normal volunteers, concomitant use of diflunisal and sulindac resulted in lowering the plasma level of the active sulfide metabolite of sulindac by approximately 33%. Sulindac is a prodrug that requires conversion to the sulfide metabolite, which is responsible for most of the pharmacologic activity.

MANAGEMENT: Concomitant use of more than one NSAID at a time should generally be avoided. Patients treated with an NSAID should be advised to take it with food and to immediately report signs and symptoms of GI ulceration and bleeding such as severe abdominal pain, dizziness, lightheadedness, and the appearance of black, tarry stools. The selective use of prophylactic anti-ulcer therapy (e.g., antacids, misoprostol, proton pump inhibitors) may be considered in high risk patients.