Lepirudin
Lepirudin (Refludan)
Lepirudin
(leh- PEER-you-din)
Pregnancy Category: B Refludan (Rx)

Classification: Anticoagulant

See Also: See also Anticoagulants.

Action/Kinetics: Recombinant hirudin from yeast cells; highly specific direct inhibitor of thrombin. One antithrombin unit (ATU) is the amount of lepirudin that neutralizes one unit of World Health Organization preparation 89/588 of thrombin. One molecule of lepirudin binds to one molecule of thrombin, blocking the thrombogenic activity of thrombin. Thus, all thrombin-dependent assays are affected (i.e., activated partial thromboplastin time--aPTT), resulting in an increase in aPTT. t 1/2, distribution: About 10 min; t 1/2, elimination: About 1.3 hr. Systemic clearance is dependent on glomerular filtration rate. About half is excreted in the urine as unchanged drug and other fragments. Dose must be adjusted based on C _CR.

Uses: Treat heparin-induced thrombocytopenia and associated thromboembolic disease to prevent further complications.

Contraindications: Hypersensitivity to hirudins. Lactation.

Special Concerns: Assess risk of therapy in those with an increased risk of bleeding, including recent puncture of large vessels or organ biopsy; anomaly of vessels or organs; recent CVA, stroke, intracerebral surgery or other neuraxial procedures; severe uncontrolled hypertension; bacterial endocarditis; advanced renal impairment; hemorrhagic diathesis; recent major surgery; recent intracranial, GI, intraocular, or pulmonary major bleeding. Formation of antihirudin antibodies or serious hepatic injury may increase the anticoagulant effect. Increased risk of allergic reactions in those also receiving thrombolytic therapy (e.g., streptokinase) for acute MI or contrast media for coronary angiography. Safety and efficacy have not been determined in children.

Side Effects: Hemorrhagic events: Bleeding from puncture sites and wounds, anemia or isolated drop in hemoglobin, hematoma, hematuria, GI and rectal bleeding, epistaxis, hemothorax, vaginal bleeding, intracranial bleeding, hemoperitoneum, hemoptysis, liver bleeding, lung bleeding, mouth bleeding, retroperitoneal bleeding. CV: Heart failure, pericardial effusion, ventricular fibrillation. Allergic reactions: Cough, bronchospasms stridor, dyspnea, pruritus, urticaria, rash, flushes, chills, anaphylaxis angioedema, facial/tongue/larynx edema. Miscellaneous: Fever, abnormal liver function, pneumonia, sepsis, allergic skin reactions, abnormal kidney function, unspecified infections, multiorgan failure.

Overdose Management: Symptoms: Bleeding. Treatment: Immediately stop administration. Determine aPTT and other coagulation levels as appropriate. Determine hemoglobin and prepare for blood transfusion. Follow guidelines for treatment of shock. Hemofiltration or hemodialysis may be helpful.

Drug Interactions: Coumarin derivatives / Risk of bleeding Thrombolytics (streptokinase, tPA) / Risk of bleeding complications and effect on aPTT prolongation

How Supplied: Powder for Injection: 50 mg

Dosage
?IV Heparin-induced thrombocytopenia and associated thromboembolic disease.
Adults, initial: 0.4 mg/kg given slowly over 15-20 seconds as a bolus dose followed by 0.15 mg/kg/hr as a continuous IV infusion for 2-10 days or longer if needed. The maximum bolus dose is 44 mg and the maximal initial infusion dose is 16.5 mg/hr. Adjust dose according to the aPTT ratio (client aPTT at a given time over an aPTT reference value, usually median of the lab normal range for aPTT).
The bolus and infusion doses must be reduced in known or suspected renal insufficiency (C _CR less than 60 mL/min or serum creatinine greater than 1.5 mg/dL).
Concomitant use with thrombolytics.
Initial IV bolus: 0.2 mg/kg; continuous IV infusion: 0.1 mg/kg/hr.