Drug Interactions between aspirin / omeprazole and betrixaban

MONITOR CLOSELY: Concomitant use of betrixaban with other agents that alter hemostasis such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), platelet aggregation inhibitors, other anticoagulants, thrombolytic agents, or drugs that cause thrombocytopenia may increase the risk of bleeding. In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during betrixaban therapy may also be increased by the concomitant use of other drugs that affect coagulation. The development of epidural and spinal hematoma can lead to long-term neurological injury or permanent paralysis.

MANAGEMENT: Caution is recommended if betrixaban must be used with other agents that alter hemostasis. Some authorities consider concomitant treatment with other anticoagulants to be relatively contraindicated except under special circumstances such as switching oral anticoagulant therapy, or when unfractionated heparin is used at doses required to maintain a patent central venous or arterial catheter. Patients should be monitored for increased anticoagulant effects and bleeding complications. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with caution and only after thorough assessment of risks and benefits. Besides bleeding complications, patients should also be monitored frequently for signs and symptoms of neurologic impairment such as midline back pain, sensory and motor deficits (numbness or weakness in lower limbs), and bowel or bladder dysfunction.

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.