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Pronunciation: LEP-ih-ruh-din
Class: Thrombin inhibitor

Trade Names

- Powder for Injection 50 mg


One molecule of lepirudin (rDNA) binds to 1 molecule of thrombin and blocks the thrombogenic activity of thrombin.

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Following IV administration, distribution follows a 2–compartment model with an initial half-life of approximately 10 min.


Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis.


Elimination follows first order kinetics and is characterized by a terminal t ½ of approximately 1.3 h. About 48% of the administered dose is excreted in the urine (35% unchanged).

Special Populations

Renal Function Impairment

In patients with marked renal insufficiency (CrCl less than 15 mL/min) and on hemodialysis, the elimination t ½ is prolonged up to 2 days.


Systemic Cl is 20% lower in elderly than in younger patients.


Systemic Cl is about 25% lower in women than men.

Indications and Usage

Anticoagulation in patients with heparin-induced thrombocytopenia and associated thromboembolic disease to prevent further thromboembolic complications.

Unlabeled Uses

Adjunct therapy for treatment of unstable angina; acute MI without ST elevation; prevention of deep vein thrombosis; patients undergoing percutaneous coronary intervention.


Hypersensitivity to hirudins or any component of the product.

Dosage and Administration

Heparin-Induced Thrombocytopenia

IV 0.4 mg/kg (up to 110 kg body weight) slowly (eg, over 15 to 20 sec) as a bolus followed by 0.15 mg/kg (up to 110 kg of body weight)/h as a continuous IV infusion for 2 to 10 days or longer if clinically needed.

Dose Modification

IV If the confirmed APTT ratio is below the target range, increase the infusion rate in steps of 20% and determine the APTT ratio again 4 h later. Do not exceed an infusion rate of 0.21 mg/kg/h without checking for coagulation abnormalities that might prevent an appropriate APTT response. If the confirmed APTT ratio is above the target range, stop the infusion for 2 h. At restart, decrease the infusion 50% and determine the APTT ratio again 4 h later.

Renal Function Impairment

IV Reduce the dose if there is known or suspected renal function impairment (CrCl less than 60 mL/min or serum creatinine above 1.5 mg/dL). In addition to monitoring renal status, APTT monitoring should be used. In all patients with renal function impairment, the bolus dose is to be reduced to 0.2 mg/kg. Reduce the standard initial infusion rate as follows— CrCl 45 to 60 mL/min or serum creatinine 1.6 to 2 mg/dL— Administer at 50% of the standard infusion rate (0.075 mg/kg/h). CrCl 30 to 44 mL/min or serum creatinine 2.1 to 3 mg/dL— Administer at 30% of the standard infusion rate (0.045 mg/kg/h). CrCl 15 to 29 mL/min or serum creatine 3.1 to 6 mg/dL— Administer at 15% of the standard infusion rate (0.0225 mg/kg/h). Less than 15 mL/min or serum creatine greater than 6 mg/dL— Avoid or stop infusion.

Concomitant Use of Thrombolytic Therapy

IV Initial bolus of 0.2 mg/kg followed by continuous infusion of 0.1 mg/kg/h.

Switching to Oral Anticoagulants

Gradually reduce the lepirudin dose to reach an APTT ratio just above 1.5 before initiating oral anticoagulation. Initiate coumarin derivatives only when platelet counts are normalizing. Start maintenance dose with no loading dose. To avoid prothrombotic effects when initiating coumarin, continue parenteral anticoagulation for 4 to 5 days.

General Advice

  • For IV administration only. Not for intradermal, IM, or subcutaneous administration.
  • Follow manufacturer's instructions for reconstitution of powder and dilution of reconstituted solution.
  • Use reconstituted solution immediately. Discard any unused infusion solution after 24 h.
  • Refer to manufacturer's insert for compatibility with IV fluids and other medications.
  • Do not administer if solution is cloudy, discolored, or contains particulate matter.
  • Warm solution to room temperature before administration.
  • Ensure that baseline hematocrit or hemoglobin, platelet count, and APTT ratio (patient APTT over APTT reference value) are performed and evaluated prior to starting therapy.
  • Do not initiate therapy if baseline APTT ratio is 2.5 or more.
  • Ensure that APTT ratio is determined 4 h after start of therapy and after every dosage adjustment, and at least every 24 h thereafter during therapy.
  • Ensure more frequent APTT monitoring in patients with renal impairment or serious liver injury.
  • Ensure that dosage is adjusted to maintain APTT ratio between 1.5 and 2.5 following manufacturer's recommendations for dosage adjustments.


Store unopened vials in refrigerator (36° to 46°F) or at controlled room temperature (59° to 77°F). Reconstituted solution remains stable for up to 24 h at room temperature (eg, during infusion).

Drug Interactions

Coumarin derivatives (eg, vitamin K antagonists), thrombolytics (eg, alteplase, streptokinase)

Risk of bleeding may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Heart failure (2%).


Bleeding from puncture sites and wounds (11%); allergic skin reactions (4%).


Epistaxis (4%).


GI and rectal bleeding (5%).


Hematuria (4%); vaginal bleeding (2%).


Anemia or isolated drop in hemoglobin (12%); sepsis (4%).


Abnormal liver function (5%).


Abnormal renal function (2%).


Pneumonia (4%).


Hematoma or unclassified bleeding (11%); fever, multiorgan failure (4%); unspecified infections (2%); intracranial bleeding; allergic reactions (including cough, bronchospasm, stridor, dyspnea [1% to less than 10%]); anaphylactic reactions (postmarketing).



Category B .




Safety and efficacy not established.


Allergic and hypersensitivity reactions, including anaphylaxis (resulting in shock or death), can occur.

Renal Function

Adjust the dose as indicated.

Hepatic Function

May enhance the anticoagulant effect.

Hemorrhagic events

Hemorrhagic events may occur at any site. Monitor patient for signs of bleeding throughout therapy. If bleeding develops (eg, epistaxis; hematuria; hematemesis; bloody or black, tarry stools) or is suspected (eg, unexplained fall in hematocrit or BP or any unexplained symptoms), notify health care provider immediately.

Intracranial bleeding

Life-threatening intracranial bleeding may occur with coadministration of thrombolytic therapy (eg, alteplase, streptokinase).




Patient Information

  • Advise patient, family, or caregiver that medication will be prepared and administered by a health care professional in a hospital setting.
  • Instruct patient, family member, or caregiver to report any signs of bleeding or allergic reaction immediately.

Copyright © 2009 Wolters Kluwer Health.