Pradaxa Side Effects

Pradaxa Side Effects: Generic name: dibigatran. The usual dose of Pradaxa is 150 mg twice daily, but the dose should be lowered to 75 mg twice daily in patients with a creatinine clearance of 15-30 ml/min. Pradaxa is a direct thrombin inhibitor approved by the FDA as an oral anticoagulant for use for stroke prevention in atrial fibrillation without valvular heart disease. In the months since Pradaxa FDA approval the use of Pradaxa has been increasing as more experience with using Pradaxa becomes available and as physicians become more comfortable with Pradaxa side effects. In the studies of Pradaxa that led to FDA approval the incidence of Pradaxa side effects involving bleeding into the brain appear to be less than with use of warfarin, and gastrointestinal bleeding seems to be slightly more common than with warfarin. The primary advantage of Pradaxa vs. warfarin is that the need for frequent monitoring of INR is not necessary with Pradaxa, but is imperative in patients using warfarin to assure efficacy and avoid bleeding side effects from excess anticoagulation.

Common Pradaxa Side Effects: There are remarkably few common Pradaxa side effects. Bleeding, dyspepsia and gastritis are the only three Pradaxa side effects considered common, but bleeding is also the major serious Pradaxa side effect that concerns patients and physicians.

Serious Pradaxa Side Effects: Serious Pradaxa side effects are primarily the anticipated risks of serious bleeding and especially gastrointestinal bleeding. In the primary studies of Pradaxa as compared to warfarin the incidence of serious central nervous system bleeding was lower in Pradaxa than in warfarin. In addition the efficacy of Pradaxa at stroke prevention in atrial fibrillation, the lone FDA approved Pradaxa indication at this time was at least a good, possibly slightly better, than warfarin. The incidence of serious gastrointestinal bleeding seemed to be slightly higher in Pradaxa vs. warfarin. Other potentially serious Pradaxa side effects include hypersensitivity and anaphylactic reactions.

Cautions and Drug Interactions: The list of potential drug interactions with Pradaxa is extensive and readers should refer to the manufacturer’s prescribing guidelines for complete details. Pradaxa is contraindicated in patients with active bleeding, anticipated major surgery, or who are at high risk for bleeding. Pradaxa is contraindicated for use with mifepristone, and use with other anticoagulants like warfarin and heparin requires special caution. Many of the antiretroviral HIV drugs interact with Pradaxa, as does St. John’s Wort and carbamazepine. Use of Pradaxa with antiplatelet drugs like aspirin and Plavix may increase bleeding risk and requires an evaluation of the risks vs. benefits. Use with the NSAID medications and COX2 inhibitors, both of which can cause GI bleeding makes the risk of serious bleeding higher. Many herbal supplements may interact with Pradaxa, and use of evening primrose oil, fenugreek, feverfew, garlic, ginger, ginkgo biloba, ginsent, green tea, willow bark and horse chestnut seed is likely best avoided. Use with any of the SSRI medications may interfere with Pradaxa metabolism.

Pradaxa use in Pregnancy and Lactation: Pradaxa is pregnancy category C, and safety in lactation is unknown.

Special Considerations: When transitioning a patient to Pradaxa from warfarin, Pradaxa should not be started until the INR is less than 2.0. When moving to Pradaxa from a parenteral anticoagulant like Heparin or low molecular weight heparin start Pradaxa 0-2 hours prior to the next anticipated dose of the low molecular weight heparin or after stopping the heparin infusion.

Management with Bleeding: Unlike warfarin where anticoagulation effects can be reversed emergently with fresh frozen plasma or clotting factor replacement, with Pradaxa there is no emergent antidote. Fortunately the half life of Pradaxa is relatively short, and the anticoagulant effect lasts only about a day after the last dose, making the effect of Pradaxa much shorter acting than warfarin. The risks of reversing warfarin with fresh frozen plasma or cryoprecipitate in many cases may be as high as the risks of support of the patient through the relatively few hours until the Pradaxa is metabolized and its effect wanes without active intervention.

The primary issue with Pradaxa use at this time may be cost. The cost of purchase of Pradaxa is considerably higher than the cost of warfarin, although much if not all of this cost may be offset by the savings from not needing frequent INR monitoring and by a lower risk of stroke and CNS bleeding.