LEPIRUDIN

(le-pir'u-din)

Refludan
Classifications: anticoagulant; direct thrombin inhibitor;
Therapeutic: antithrombotic; anticoagulant
Pregnancy Category: B

Availability

50 mg powder for injection

Action

Highly specific direct inhibitor of thrombin, including thrombin entrapped within established clots. One molecule of lepirudin binds to one molecule of thrombin and thereby blocks the thrombogenic activity of thrombin. Increases PT/INR and aPTT values in relation to the dose given.

Therapeutic Effect

Has antithrombotic activity; its 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; intracranial bleeding; patients with increased risk of bleeding (e.g., recent surgery, CVA, advanced kidney impairment); lactation. Safety and efficacy in children not established.

Cautious Use

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

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

Renal Impairment
Cl_cr 45–60 mL/min: initial dose 0.2 mg/kg, then 0.075 mg/kg/h; 30–44 mL/min: initial dose 0.2 mg/kg then 0.045 mg/kg/h; 15–29 mL/min: initial dose 0.2 mg/kg, then 0.0225 mg/kg/h; <15 mL/min: do not use

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: By catabolic hydrolysis in serum. Elimination: 48% 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.

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

(68)