LEPIRUDIN

(le-pir'u-din)
Refludan
Classifications: blood formers, coagulators, and anticoagulants; direct thrombin inhibitor; anticoagulant
Pregnancy Category: B

Availability

50 mg powder for injection

Actions

Highly specific direct inhibitor of thrombin. One molecule of lepirudin binds to one molecule of thrombin and thereby blocks the thrombogenic activity of thrombin.

Therapeutic Effects

Increases PT/INR and aPTT values in relation to the dose given. Effectiveness is indicated by aPTT ratio in target range of 1.5 to 2.5.

Uses

Anticoagulation in patients with heparin-induced thrombocytopenia (HIT).

Contraindications

Hypersensitivity to lepirudin; lactation; pregnancy (category B); intracranial bleeding; patients with increased risk of bleeding (e.g., recent surgery, CVA, advanced kidney impairment). Safety and efficacy in children not established.

Cautious Use

Serious liver injury (e.g., cirrhosis); concomitant administration with streptokinase; renal impairment.

Route & Dosage

Anticoagulation
Adult: IV 0.4 mg/kg initial bolus (max: 44 mg) followed by 0.15 mg/kg/h (max: 16.5 mg/h) for 2–10 d, adjust rate to maintain aPTT of 1.5–2.5

Administration

Intravenous

PREPARE: Direct: Reconstitute by adding 1 mL of sterile water for injection or NS to the 50-mg vial. To prepare bolus dose, withdraw reconstituted solution into a 10-cc syringe and dilute to 10 mL with sterile water for injection, NS or D5W to yield 5 mg/mL. Continuous: Transfer the contents of two reconstituted vials into 250 or 500 mL of D5W or NS to yield of 0.4 or 0.2 mg/mL, respectively.

ADMINISTER: Direct: Give over 15–20 sec. Continuous: Give at a rate determined by body weight.

Diluted solution is stable for 24 h during infusion. Store unopened vials at 2°–25° C (36°–77° F).

Adverse Effects (1%)

CNS: Intracranial bleeding. CV: Heart failure, ventricular fibrillation, pericardial effusion, MI. GI: Abnormal LFTs. Hematologic: Bleeding from injection site, anemia, hematoma, bleeding, hematuria, GI and rectal bleeding, epistaxis, hemothorax, vaginal bleeding. Respiratory: Pneumonia, cough, bronchospasm, stridor, dyspnea. Skin: Allergic skin reactions. Body as a Whole: Sepsis, abnormal kidney function, multiorgan failure.

Interactions

Drug: Warfarin, nsaids, salicylates, antiplatelet agents increases risk of bleeding. Herbal: Feverfew, ginkgo, ginger, valerian may potentiate bleeding.

Pharmacokinetics

Distribution: Distributed primarily to extracellular compartment. Metabolism: Metabolized by catabolic hydrolysis in serum. Elimination: 48% excreted in urine. Half-Life: 1.3 h.

Nursing Implications

Assessment & Drug Effects

Lab tests: Baseline PT/INR and aPTT prior to initiation of therapy (withhold therapy and notify physician if baseline aPTT ratio 2.5); aPTT 4 h after start of therapy and at least once daily (more often with renal or hepatic impairment) thereafter.
Give with extreme caution to those at increased risk for bleeding.
Monitor carefully for bleeding events (e.g., from puncture wounds, hematoma, hematuria); and report immediately.
Do not give oral anticoagulants until lepirudin dose has been reduced and aPTT ratio lowered to just above 1.5.

Patient & Family Education

Do not breast feed while taking this drug.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug