The Food and Drug Administration (FDA) recently approved dabigatran etexilate (Pradaxa) to reduce the risk of stroke and systemic blood clots in patients with nonvalvular atrial fibrillation.
Dabigatran inhibits free and clot-bound thrombin and thrombin-induced platelet aggregation. Thrombin allows for the conversion of fibrinogen into fibrin, creating a thrombus, or blood clot. Dabigatran prolongs the activated partial thromboplastin time (aPTT), the estimated coagulation time, and the thromboplastin time. In clinical trials conducted prior to FDA approval, participants taking dabigatran were found to have significantly fewer ischemic and hemorrhagic strokes than patients taking warfarin.
With an oral dosage of 150 mg twice a day (the drug comes in 75 and 150 mg capsules), the median aPTT is about twice that of controls. Routine monitoring of any of the laboratory tests measuring blood clotting isn't required. The international normalized ratio (INR), used to measure warfarin's effect on clotting, may or may not be elevated in a patient receiving dabigatran and, consequently, isn't very useful in measuring the drug's activity. However, in patients stopping dabigatran in order to switch to warfarin, the INR may be used as a measurement two days after the dabigatran is discontinued.
Like other drugs that prolong bleeding time and prevent clotting, dabigatran may cause serious, possibly fatal, bleeding. Patients most at risk for bleeding are those who are concurrently taking antiplatelet drugs, heparin, or fibrinolytic drugs; those with a history of long-term nonsteroidal antiinflammatory drug (NSAID) use; and pregnant women undergoing labor and delivery. (It should be noted that the clinical trials for dabigatran didn't include pregnant women. The label warning concerning pregnancy is based on the already recognized risk of bleeding in these situations; there are similar warnings on the labels of other anticoagulant and thrombolytic drugs.) In clinical trials the risk of major bleeding with dabigatran was similar to that with warfarin across most major subgroups, although risk may increase with advancing age: there was a trend toward a higher incidence of major bleeding with dabigatran, as compared with warfarin, in adults 75 years of age or older. When only gastrointestinal bleeding was considered, there was a higher rate of occurrence in patients taking dabigatran than in those taking warfarin. Because of these serious and potentially lethal adverse effects, a medication guide will be distributed with each prescription.
Gastrointestinal adverse effects other than bleeding were also more common with dabigatran than with warfarin during clinical trials. The most common were dyspepsia, stomach pain, nausea, heartburn, and bloating.
Rifampin significantly decreases the circulating levels of dabigatran; this drug combination should be avoided.
Nurses should instruct patients to swallow the capsule whole—not to break or chew it—because taking the drug without its protective coating will increase its bioavailability by 75%, which increases the likelihood of adverse effects. Instruct patients to take the drug on time. If a dose is missed, it may be taken up to six hours before the time of the next dose. Patients shouldn't double the dose. It's also important to emphasize to patients that they shouldn't stop taking the drug on their own, which can increase their risk of developing a clot and having a stroke. It may be necessary to stop the drug for a short time prior to scheduled surgery, but the timing of cessation should be determined in consultation with the health care provider who prescribed the drug.
Nurses should also teach patients prescribed dabigatran to be alert for evidence of serious bleeding (unusual bruising, pink or brown urine, red or black tar-like stools, coughing up blood, vomiting blood, or coffee-ground emesis) and seek emergency care immediately if any of these occurs. Health care providers should be notified promptly if the patient notices pain, swelling, or discomfort in a joint; headaches; dizziness or weakness; recurrent nosebleeds; unusual bleeding from the gums; bleeding from a cut that takes longer than usual to clot; or heavier than normal menstrual or vaginal bleeding. Instruct patients to avoid over-the-counter-drugs that increase the risk of bleeding, such as aspirin and other NSAIDs. Patients should also report any gastrointestinal adverse effects to the prescriber.
Finally, nurses should emphasize to patients the importance of reading the medication guide each time they have a prescription filled for the most current information on possible adverse effects.