Drug Interactions between aspirin / calcium carbonate and dasatinib

MONITOR CLOSELY: Coadministration of dasatinib and drugs that interfere with platelet function or coagulation may potentiate the risk of bleeding complications. Treatment with dasatinib is associated with severe thrombocytopenia. In addition, dasatinib has been shown to induce platelet dysfunction in vitro. Severe central nervous system hemorrhages, including fatalities, occurred in 1% of patients receiving dasatinib in clinical trials. Severe gastrointestinal hemorrhage occurred in 7% of patients and generally required treatment interruptions and transfusions. Other cases of severe hemorrhage occurred in 4% of patients. Most bleeding events were associated with severe thrombocytopenia.

MANAGEMENT: Concomitant use of other medications that interfere with platelet function or coagulation should be considered cautiously in patients treated with dasatinib. Close clinical and laboratory observation for bleeding complications is recommended during therapy. A complete blood count (CBC) with differential and platelet count should be obtained prior to and at least weekly for the first 2 months, then monthly thereafter or as clinically indicated. 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.

ADJUST DOSING INTERVAL: Nonclinical data indicate that the solubility of dasatinib is pH-dependent. Therefore, coadministration with antacids or agents with acid-neutralizing effects may reduce the oral bioavailability of dasatinib. In a pharmacokinetic study of 24 healthy subjects, administration of a 50 mg dose of dasatinib with 30 mL of aluminum hydroxide/magnesium hydroxide was associated with a 55% reduction in systemic exposure (AUC) and a 58% reduction in peak plasma concentration (Cmax) of dasatinib. However, when the same dose of aluminum hydroxide/magnesium hydroxide was administered two hours prior to the dasatinib dose, there was no significant change in dasatinib systemic exposure (AUC), and the dasatinib Cmax was increased 26%.

MANAGEMENT: Patients treated with dasatinib should avoid taking antacids or oral medications that contain antacids (e.g., didanosine buffered tablets or paediatric oral solution) for at least two hours before and two hours after administration of dasatinib.