Drug Interactions between aspirin / calcium carbonate and ibrutinib

MONITOR CLOSELY: Coadministration of ibrutinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. In clinical trials, 5% of patients with mantle cell lymphoma had Grade 3 or higher bleeding events such as subdural hematoma, gastrointestinal bleeding, and hematuria. Overall, bleeding events including bruising of any grade occurred in 48% of patients treated with ibrutinib 560 mg daily. The mechanism for the bleeding events is not well understood, although treatment with ibrutinib is associated with a high frequency of thrombocytopenia. Treatment-emergent grade 3 or 4 thrombocytopenia was reported in 17% of patients during clinical trials, while thrombocytopenia of all grades was reported in 57%. Fatal bleeding events have been reported during postmarketing use.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with ibrutinib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. The INR should be monitored more frequently during coadministration of warfarin. In addition, some authorities recommend avoiding the use of supplements that have an inhibitory effect on platelet function such as fish oil (omega-3 polyunsaturated fatty acids), flaxseed, and vitamin E preparations (AU, CA, UK) because of an increased risk of bleeding. Patients should be advised to promptly report any signs of bleeding to their physician, including pain, swelling, headache, dizziness, weakness, prolonged bleeding from cuts, increased menstrual flow, vaginal bleeding, nosebleeds, bleeding of gums from brushing, unusual bleeding or bruising, red or brown urine, or red or black stools.

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.