The anticoagulant dabigatran etexilate (Pradaxa), is a direct thrombin inhibitor approved in 2010 to reduce the risk of stroke and embolism in patients with nonvalvular atrial fibrillation. Like all anticoagulants, dabigatran increases a patient's risk of major bleeding. Warfarin (Coumadin) also increases the risk of bleeding, but dabigatran carries a higher risk of gastrointestinal bleeding, as well as a higher risk of bleeding in older adults. Until recently, there was no direct antidote for overdosage or hemorrhage related to dabigatran use. Dabigatran's labeling originally recommended surgical hemostasis or transfusion of fresh frozen plasma or red blood cells in cases of severe bleeding.
A new direct antidote to treat life-threatening or uncontrolled bleeding related to dabigatran use, idarucizumab (Praxbind), has been approved by the Food and Drug Administration (FDA). Idarucizumab can also be used prophylactically in patients taking dabigatran who need emergency surgery or other urgent procedures. Approved under an accelerated-approval program at the FDA, idarucizumab is a humanized monoclonal antibody fragment that reduces the level of unbound dabigatran and normalizes coagulation parameters but has no effect on the action of other anticoagulants.
The accelerated approval was based on data from studies in healthy volunteers. Because of an ongoing cohort study, the FDA warns in idarucizumab's labeling that the approval could be reconsidered in light of study results.
Once idarucizumab has reversed the effects of dabigatran, the patient's risks of clotting and stroke are elevated. Dabigatran therapy should be resumed 24 hours after idarucizumab is given or as soon as is medically appropriate.
The recommended dose of idarucizumab contains 4 g of sorbitol as an excipient, a substance added in a drug's formulation to protect, support, or enhance the stability of the drug; increase its bioavailability; or make it more appealing to patients, thereby increasing the likelihood of adherence. Ideally, excipients are pharmacologically inactive and nontoxic and do not interact with active ingredients or other excipients. In reality, however, excipients may produce adverse reactions in some patients. Patients with hereditary fructose intolerance who receive idarucizumab can have serious adverse reactions, including hypoglycemia, hypophosphatemia, metabolic acidosis, an increase in uric acid, acute liver or kidney failure, and even death. Death from organ failure can occur during or after injection of idarucizumab. The incidence of hereditary fructose intolerance is estimated to be one in 20,000 to 30,000 each year worldwide.
In addition to the warnings stated above, idarucizumab's labeling also warns that the drug can produce hypersensitivity reactions. The most common adverse effect seen in studies of 224 healthy volunteers was headache. In an interim report on the on-going cohort study, 123 patients (111 of whom were 65 years old or older) required reversal of dabigatran's anticoagulant effects, because they were either in need of emergency surgery or another urgent procedure or experiencing life-threatening or uncontrolled bleeding.
Adverse effects seen in these study patients included hypokalemia (in 7% of patients), delirium (7%), constipation (7%), fever (6%), and pneumonia (6%). Twenty-six of the 123 patients receiving idarucizumab died, 11 in the first day after idarucizumab dosing. The authors of the interim study reported that all of the deaths could be attributed to either a complication of the event requiring idarucizumab or associated comorbidities. Thrombotic events occurred in five of the 123 patients. One patient developed a thrombus two days after treatment with idarucizumab, and four developed a thrombus seven or more days after receiving idarucizumab. None of these patients was receiving antithrombotic treatment at the time of thrombus development.
Nurses should give the entire prescribed dose when administering idarucizumab; in order to deliver the recommended 5 g dose, two separate vials of medication, each containing 2.5 g per 50 mL, are administered. The drug is administered in either two consecutive infusions or two consecutive iv boluses. Nurses administering idarucizumab should consult the drug's labeling for complete administration directions. Because the trade names of the anticoagulant (Pradaxa) and its antidote (Praxbind) are similar, care must also be taken not to mix them up.
Nurses should ask patients whether they have been diagnosed with hereditary fructose intolerance before administering idarucizumab. If the benefit from idarucizumab therapy is deemed greater than the risk of complications from hereditary fructose intolerance, the drug can be administered, but the nurse should assess the patient carefully for adverse effects.
Complete FDA prescribing information for idarucizumab can be found at http://1.usa.gov/1QL4TG7.