Lepirudin

IV Incompatibilities

Do not mix with any other drug

IV Preparation

Reconstitute 50 mg vials with 1 mL SWI or NS, swirl gently to mix, should not take more than a few seconds

Bolus injection

• Transfer reconstituted vial contents (1 mL) into single-use syringe with at least 10 mL capacity
• Dilute with SWI, NS or D5W to total volume of 10 mL for a final concentration of 5 mg/mL

Infusion (makes 0.4 mg/mL or 0.2 mg/mL)

• Transfer 2 reconstituted vial contents to 250 mL or 500 mL of NS or D5W

IV Administration

Bolus: over 15-20 sec

See adult dosing for infusion rate

Avoid activities that may increase your risk of bleeding or injury. Use extra care to prevent bleeding while shaving or brushing your teeth.

Tell your doctor about all your current medicines and any you start or stop using, especially other medicines used to prevent blood clots, such as:

• bivalirudin, dabigatran, desirudin;
• fondaparinux, rivaroxaban; or
• heparin, dalteparin, enoxaparin, tinzaparin.

This list is not complete. Other drugs may interact with lepirudin, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Lepirudin keeps the platelets in your blood from coagulating (clotting) to prevent unwanted blood clots that can occur with certain heart or blood vessel conditions.

Lepirudin is used to treat or prevent blood clots.

Lepirudin may also be used for purposes other than those listed in this medication guide.

Your pharmacist has information about lepirudin written for health professionals that you may read.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.06. Revision date: 12/15/2010.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

Distribution

Extent

Confined to extracellular fluids with a distribution half-life of approximately 10 minutes.1 Volume of distribution at steady state in healthy young adults is 12.2 L.1 Volume of distribution at steady state in patients with HIT is 32.1 L.1

Crosses the placenta in animals.1 Not known whether lepirudin crosses the placenta in humans or is distributed into human milk.1

Special Populations

Volume of distribution at steady state in healthy geriatric individuals is 18.7 L.1

Volume of distribution at steady state in patients with renal impairment is 18 L.1

Elimination

Metabolism

Thought to be metabolized by release of amino acids via catabolic hydrolysis.1

Elimination Route

Eliminated principally by the kidneys.1 13 Excreted in urine (48%) as unchanged drug (35%) and metabolites.1 Systemic clearance proportional to the GFR or Clcr.1 Systemic clearance is 164 mL/minute in healthy young individuals.1

Half-life

Terminal half-life is approximately 1.3 hours.1 Systemic clearance is lower (about 25%) in women than in men.1

Special Populations

Prolonged elimination half-life (up to 2 days) in patients with marked renal insufficiency (i.e., Clcr <15 mL/minute) who require hemodialysis.1

Systemic clearance is 20% lower in geriatric patients than in younger patients.1

• Specific, direct thrombin inhibitor; binds irreversibly13 to circulating and clot-bound thrombin.1 2 3 4 6 13

• Prevents various steps in the coagulation process (e.g., activation of factors V, VIII, and XIII and of protein C; conversion of fibrinogen to fibrin; platelet activation and aggregation).2

• Affects all coagulation assays dependent on thrombin; increases aPTT in a dose-dependent manner.1

• Risk of serious bleeding or hemorrhage.1

• Importance of reporting any signs of bleeding (e.g., bruising, petechiae, hematuria) to clinician immediately.1

• Importance of patients informing clinician of history of bleeding disorders or impaired renal function.1

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.1

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.1

• Importance of informing patients of other important precautionary information. (See Cautions.)

Applies to lepirudin: intravenous powder for injection

Hematologic

Other hemorrhagic events (hemoperitoneum, hemoptysis, liver bleeding, lung bleeding, mouth bleeding, retroperitoneal bleeding) each occurred in one individual among 198 patients treated with lepirudin in controlled trials.[Ref]

Hemorrhagic events have been the most common and potentially serious side effects associated with the use of lepirudin. The following were reported during controlled trials: bleeding from puncture sites and wounds (10.6% to 14.1%); anemia or isolated drop in hemoglobin concentration (12.4% to 13.1%); hematoma or unclassified hemorrhage (10.6% to 11.1%); gastrointestinal or rectal bleeding (5.1% to 5.3%); epistaxis (3.0% to 4.4%); hemothorax (0% to 3.0%); vaginal bleeding (1.5% to 1.8%); intracranial bleeding (0%). Intracranial hemorrhage (ICH) has been observed in patients with acute myocardial infarction who were started on both thrombolytic therapy and lepirudin. The overall prevalence of ICH in this population was 0.6% (7 of 1134 patients). ICH was not observed among 1168 patients who did not receive concomitant thrombolytic therapy. There has been at least one case report of thrombocytopenia.[Ref]

Hypersensitivity

Serious anaphylactic reactions resulting in shock or death have been reported.[Ref]

Hypersensitivity reactions have occurred in up to 10% of patients and have included skin rashes, pruritus, urticaria, flushing, or chills (less than 1.0% to 3.5%) and airway reactions, such as cough, bronchospasm, stridor, dyspnea (up to 10%). Anaphylaxis or anaphylactoid reactions have been observed in less than 1% of patients. Approximately 53% of allergic or suspected allergic reactions occurred in patients also receiving thrombolytic therapy for acute myocardial infarction and/or contrast media for coronary angiography.[Ref]

Immunologic

Antihirudin antibodies have been reported in approximately 40% of heparin-induced thrombocytopenia patients receiving lepirudin. Complexation of lepirudin to these antibodies may increase the anticoagulant effect due to delayed renal elimination of active complexes. Lepirudin neutralization and allergic reactions have not been reported despite positive antibody tests. Adverse reactions following reexposure have been limited to mild skin reactions.[Ref]

Respiratory

Respiratory effects as a result of hypersensitivity reactions have been reported in up to 10% of patients. Symptoms included cough, bronchospasm, stridor, and dyspnea. Pneumonia has occurred in up to 4.4% of patients compared with 5.5% in control patients.[Ref]

Hepatic

Abnormal elevations of liver transaminases and other measurements of liver function have been reported in approximately 6% of patients.[Ref]

General

General side effects have included fever (4% to 6% of patients) and unspecified allergic reactions (less than 1% of patients).

The prevalence of sepsis, unspecified infections, and multiorgan failure has been similar among treated versus control patients (4.0% versus 5.5%, 2.5% versus 1.1%, and 2.0% versus 0%, respectively).[Ref]

Cardiovascular

Cardiovascular side effects have included new or worsened heart failure in up to 3% of patients. Pericardial effusion and ventricular fibrillation each have been reported in 1% of patients. Edema (facial, tongue, laryngeal, or angioedema) has been associated rarely with use of lepirudin.[Ref]

Renal

New or worsened renal insufficiency has been observed in 1.8% to 2.5% of patients versus 4.4% among control patients.[Ref]

Some side effects of lepirudin may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Lepirudin has been assigned to FDA pregnancy category B by the FDA. Animal data failed to reveal evidence of teratogenicity or fetotoxicity after doses 1.2 and 2.4 times the maximum recommended daily human dosage (controlled for body size). Limited data revealed evidence of increased maternal mortality with these doses. There are no adequate or controlled data from human pregnancy. Lepirudin should be given during pregnancy only when need has been clearly established.

LactMed Record Number

154

Last Revision Date

20151106

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.