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  1. Devlin, Melissa M. RPh, PharmD

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The first direct thrombin inhibitor approved by the FDA, lepirudin (Refludan) is indicated for anticoagulation and to prevent further thromboembolic complications in patients with heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease. The dosage is based on the patient's body weight and activated partial thromboplastin time (aPTT). The most common adverse reaction is bleeding, so careful administration and dosing is important.




Q. How does lepirudin work?


A. Lepirudin, a biosynthetic molecule, is a highly specific direct thrombin inhibitor that's similar to natural hirudin. Lepirudin binds to thrombin and antagonizes its action, even within established clots. Unlike heparin, lepirudin works independent of antithrombin III and isn't inhibited by platelet factor 4.


Lepirudin is given I.V. About half of the drug is excreted in the urine. Systemic clearance, which is proportional to glomerular filtration rate, is about 25% lower in women than in men and about 20% lower in older adults than younger adults. The elimination half-life is about 1.3 hours but can be prolonged up to 2 days in patients with renal failure.



Q. Who shouldn't use lepirudin?


A. Lepirudin is contraindicated in patients with known hirudin hypersensitivity or hypersensitivity to any of lepirudin's components. It should be used during pregnancy only if clearly needed.


The drug may be excreted in human milk, so a woman who's breast-feeding should either stop breast-feeding or stop lepirudin, based on an assessment of risks and benefits in her case. Lepirudin's safety and efficacy haven't been established in children.


Severe liver impairment may increase lepirudin's effects. No dosage adjustment is needed, but monitor the patient's response to treatment closely. Renal impairment can cause buildup of lepirudin; see the prescribing information for recommended dose adjustments.



Q. How is lepirudin supplied and administered?


A. Lepirudin is supplied as a powder in 50-mg vials. Store the unopened vials at 2[degrees] to 25[degrees] C (35.6[degrees] to 77[degrees] F). See the prescribing information for details on reconstituting lepirudin. Once reconstituted, use immediately.


For anticoagulation in adults with HIT, give a slow I.V. bolus followed by a continuous infusion. The initial dosage is 0.4 mg/kg for patients weighing up to 242.5 pounds (110 kg), followed by an infusion of 0.15 mg/kg/hour for 2 to 10 days or longer if indicated. See the prescribing information for details on adjusting the dosage and for reducing the dosage in patients with impaired renal function.



Q. What precautions should I be aware of?


A. About 40% of patients with HIT who are treated with lepirudin develop antihirudin antibodies. These antibodies may increase lepirudin's anticoagulation effects, possibly due to delayed renal elimination. Monitor the patient's aPTT closely.


Patients who've received a fibrinolytic drug should start lepirudin at a lower initial dosage to reduce the risk of bleeding. See the prescribing information for details.



Q. How should I monitor a patient who's receiving lepirudin?


A. Because of the bleeding risk, check for bleeding around injection and puncture sites and wounds. Monitor hemoglobin, hematocrit, aPTT, platelet count, fecal occult blood test, urinalysis, and blood pressure. For dosage adjustments, also monitor the patient's serum creatinine.



Q. What are possible adverse reactions to lepirudin?


A. In clinical trials, the most common adverse reactions were bleeding from injection and puncture sites, wounds, gastrointestinal tract, nose, and vagina; anemia; hematoma; and intracranial hemorrhage. Less common problems included airway reactions, abnormal liver or kidney function, pneumonia, sepsis, allergic skin reactions, heart failure, multiorgan failure, pericardial effusion, ventricular fibrillation, and hypersensitivity reactions.




Refludan prescribing information. http://www.refludan.com/index.jsp.