Drug Interactions between dabigatran and famotidine / ibuprofen

MONITOR CLOSELY: Coadministration of thrombin inhibitors with drugs that affect platelet function may potentiate the risk of bleeding due to additive or synergistic effects on hemostasis.

GENERALLY AVOID: In patients receiving neuraxial anesthesia or spinal puncture, the risk of developing an epidural or spinal hematoma during thrombin inhibitor therapy may be increased by the concomitant use of other drugs that affect coagulation, including nonsteroidal anti-inflammatory drugs (NSAIDs) and platelet inhibitors. The development of epidural and spinal hematoma can lead to long-term or permanent paralysis.

MANAGEMENT: Close clinical and laboratory observation for bleeding complications is recommended if thrombin inhibitors are used with drugs that interfere with platelet function, including long-term or chronic NSAIDs. In patients undergoing neuraxial intervention, coadministration of these agents should be approached with extreme caution and only after thorough assessment of risks and benefits. Besides bleeding complications, these 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. Urgent diagnosis and treatment (e.g., spinal cord decompression) are required if signs or symptoms of spinal hematoma develop. To reduce the potential risk of bleeding, placement or removal of an epidural catheter or lumbar puncture should ideally be performed when the anticoagulant effect of the thrombin inhibitor is low. An optimal interval has not been established, but should take into consideration the pharmacokinetic profile of the thrombin inhibitor.

MONITOR: Patients with gastrointestinal conditions may have an increased risk of gastrointestinal bleeding during concomitant treatment with dabigatran etexilate and proton pump inhibitors or H2 blockers. In addition, pantoprazole resulted in an approximately 30% decrease in dabigatran systemic exposure (AUC). Diminished clinical effect may occur, although no dosage adjustment is recommended for dabigatran etexilate. The pharmacokinetics of pantoprazole were not significantly altered by dabigatran. Pantoprazole and other proton pump inhibitors were also coadministered with dabigatran in clinical trials for the prevention of venous thromboembolic events after hip- or knee-replacement surgery, and no effects on bleeding or efficacy were observed. Ranitidine had no significant effects on the absorption of dabigatran.

MANAGEMENT: Patients should be monitored for signs of gastrointestinal bleeding and advised to promptly report any symptoms to their physician, such as abdominal pain, dizziness, lightheadedness, vomiting blood, anorexia, and/or black, tarry stools.

H2 antagonists may alter the pharmacokinetic disposition of some nonsteroidal anti-inflammatory drugs (NSAIDs), resulting in increased or decreased plasma concentrations. Data have been varied, even for the same NSAID. The mechanism may involve inhibition of metabolism, changes in gastric pH resulting in altered absorption, and/or reduced urinary elimination of the affected NSAIDs. Statistically significant changes have been small and of limited clinical significance when interactions have been observed.