Drug Interactions between asparaginase erwinia chrysanthemi and Yosprala

MONITOR: Asparaginase therapy may lead to imbalances in coagulation factors predisposing the patient to bleeding or thrombosis. Theoretically, concurrent use of anticoagulants and asparaginase may increase the risk of bleeding. Hemorrhages grade 3 and above and CNS hemorrhages have been observed with asparaginase treatment. However, serious thromboembolic events have also been reported with the use of asparaginase. Some investigators have suggested that anticoagulants could be used prophylactically with asparaginase for the prevention of thromboembolic events.

MANAGEMENT: Coagulation parameters should be monitored at baseline and periodically during concomitant treatment with asparaginase and anticoagulants such as heparin, dipyridamole, aspirin and nonsteroidal anti-inflammatory drugs. Patients should be advised to promptly report any signs and symptoms of bleeding.

Coadministration with proton pump inhibitors may decrease the oral bioavailability of aspirin and other salicylates. The interaction has been studied with omeprazole and aspirin, although data are conflicting. In one study, pretreatment with omeprazole (20 mg/day for 2 days) in 11 healthy volunteers led to a significant and progressively greater reduction in the mean serum salicylate level at 30, 60, and 90 minutes after administration of aspirin (650 mg single dose). The investigators suggest that acid suppression may reduce the lipophilic nature of aspirin, thereby adversely affecting its absorption from the gastrointestinal tract. Another study found no effect of omeprazole pretreatment (20 mg/day for 4 days) on plasma salicylate and aspirin levels, skin bleeding times, or antiplatelet effect of low-dose aspirin (125 mg single dose) in 14 healthy volunteers. However, these results do not exclude the possibility that omeprazole might interfere with the analgesic, antipyretic, or anti-inflammatory effects of aspirin, which has been demonstrated in rats.

Proton pump inhibitors may enhance the release rate of salicylates from enteric-coated formulations due to premature disruption of the coating and intragastric release of the drug secondary to an increase in gastric pH. In eight healthy volunteers, omeprazole pretreatment (20 mg/day for 4 days) did not affect the bioavailability of salicylate from uncoated aspirin tablets but significantly increased the absorption rate of salicylate from enteric-coated sodium salicylate tablets. The clinical significance of this interaction is unknown. Theoretically, it may increase the risk of gastric adverse effects associated with salicylates.