Drug Interactions between aspirin / calcium carbonate and sulfinpyrazone

GENERALLY AVOID: Salicylates may antagonize the uricosuric effect of sulfinpyrazone. The exact mechanism of interaction is unknown, although therapeutic doses of aspirin have been shown to increase plasma clearance of sulfinpyrazone. In one study, acute pretreatment with aspirin (325 mg four times a day for 24 hours) resulted in increased plasma clearance of a single 400 mg dose of sulfinpyrazone in 5 of 6 subjects by 12% to 27% relative to administration of sulfinpyrazone alone. When sulfinpyrazone 200 mg and aspirin 325 mg were coadministered four times a day for one week, plasma clearance of sulfinpyrazone increased up to 229%. The investigators theorized that aspirin may displace sulfinpyrazone from plasma protein binding sites, resulting in a redistribution of sulfinpyrazone into peripheral compartments and increased amount of free drug for hepatic metabolism. In vitro data also suggest that sulfinpyrazone may interfere with the irreversible effects of aspirin (especially low doses) on platelets, although the clinical significance is unknown.

MANAGEMENT: Salicylates should not be used during sulfinpyrazone therapy for gouty arthritis. However, occasional small doses of salicylates are not expected to interact significantly.

MONITOR: Chronic administration of antacids may reduce serum salicylate concentrations in patients receiving large doses of aspirin or other salicylates. The mechanism involves reduction in salicylate renal tubular reabsorption due to urinary alkalinization by antacids, resulting in increased renal salicylate clearance. In three children treated with large doses of aspirin for rheumatic fever, serum salicylate levels declined 30% to 70% during coadministration with a magnesium and aluminum hydroxide antacid. Other studies have found similar, albeit less dramatic results. Antacids reportedly have no effect on the oral bioavailability of aspirin in healthy adults. However, administration of antacids containing either aluminum and magnesium hydroxide or calcium carbonate two hours before aspirin dosing led to reduced absorption of aspirin in uremic patients.

MANAGEMENT: Patients treated chronically with antacids (or oral medications that contain antacids such as didanosine buffered tablets or pediatric oral solution) and large doses of salicylates (i.e. 3 g/day or more) should be monitored for potentially diminished or inadequate analgesic and anti-inflammatory effects, and the salicylate dosage adjusted if necessary.