Drug Interactions between aspirin / caffeine / dihydrocodeine 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.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.