Lepirudin

Lepirudin is a prescription drug used to reduce blood clotting (thromboembolism) in people with heparin-induced thrombocytopenia (HIT) or related thrombocytopenias. HIT is low blood platelet count (thrombocytopenia) that results from taking the medication heparin. It is also used to reduce the risk of clots during acute coronary syndromes (ACS), which is a sudden onset of chest pain and/or a heart attack. Lepirudin is a genetically-engineered form of hirudin. Natural hirudin is produced by the leech Hirudo medicinalis. Hirudin is one of the compounds responsible for the leech's ability to prevent clotting while "sucking blood". The Food and Drug Administration approved lepirudin on March 6, 1998. Lepirudin is marketed as Refludan by Bayer.

The medicinal leech Hirudo medicinalis.

Uses

Lepirudin is used to reduce the risk of blood clots in adults with either HIT or ACS. For the latter, lepirudin is given in combination with acetylsalicylic acid (aspirin).

How Lepirudin is Taken

Lepirudin is available in a vial for intravenous (IV) infusion. The dose is dependent on body weight up to a weight of 110 kg (243 lbs). People over 110 kg receive a dose equivalent to that used for 110 kg. Lepirudin is first infused at a dose of 0.4 mg/kg over 15–20 seconds. Subsequently, 0.15 mg/kg per hour is infused continuously for 2–10 days, or longer if needed. Dosing is adjusted thereafter based on the ability of the blood to clot.

How Lepirudin Works

Thrombin is an enzyme in the blood, outside of cells, that initiates clotting by cleaving proteins. Lepirudin is an anticoagulant that inhibits thrombin and prevents blood clots.

How the Body Affects Lepirudin

The half-life of lepirudin, or the time needed for the concentration of the drug in the blood to be reduced by half, is approximately 1.6 hours. Lepirudin is believed to be broken down into its individual amino acid components in the kidneys. About 48% of the original dose is excreted in the urine (35% unchanged drug and the remainder as fragments).

Side Effects

Excessive bleeding is the most common side effect of lepirudin. Other common side effects, occurring in more than 1% of people, include the following:

• fever
• abnormal liver function
• allergic skin reactions
• infections
• organ failure

Risks and Precautions

Due to its anti-blood clotting effects, lepirudin can cause hemorrhage. The following conditions increase the risk of hemorrhage during treatment with lepirudin:

• recent puncture of large blood vessels or organ biopsy
• anomalies in the structure of blood vessels or organs
• recent stroke, brain surgery, or other brain procedures
• severe, uncontrolled high blood pressure
• bacterial endocarditis (bacterial infection involving the inner lining or valves of the heart)
• advanced kidney impairment
• recent major surgery
• recent major bleeding (e.g, in the grain, abdomen, eyes, or lungs)
• recent, active peptic ulcer

An overdose may occur in patients with kidney impairment, even at standard doses of lepirudin. Accumulation of the drug increases the risk of bleeding. Dose adjustments can lower the risk of bleeding.

The risk of bleeding complications may be increased by severe liver damage, which impairs the ability of the blood to clot and thus has an additive effect with administration of lepirudin.

Some people produce antibodies to lepirudin. These antibodies are produced by the body’s immune system in response to a foreign protein. Periodic blood tests that monitor blood clotting reduce the risk of developing complications due to antibody production.

Drug Interactions

Concomitant use of drugs that prevent blood clotting increases the risk of excessive bleeding or hemorrhage. Some of these include drugs that break up clots, called thrombolytics (e.g., rt-PA or streptokinase), coumarin derivatives (e.g., warfarin), and drugs that affect the activity of platelets (e.g., clopidogrel (Plavix)).

Research

The HIT-1 clinical trial showed that lepirudin reduced the combined risk of death, limb amputation, and complications due to blood clotting by 73%.^[1]

The HIT-4 trial compared the effects of lepirudin and heparin on heart attack outcomes.^[2] Lepirudin and heparin were equally effective in resolving a heart attack (approximately half the patients improved in both treatment groups). Moreover, the rates of stroke, death, and bleeding episodes were similar between the two treatment groups.

References

1. ↑ Gibson TB, Ranganathan A, Grothey A. Heparin-induced thrombocytopenia with thromboembolic complications: meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range. Clin Colorectal Cancer. 2006 May;6(1):29-31. Abstract | Full Text | PDF
2. ↑ Neuhaus KL, Molhoek GP, Zeymer U, et al. Recombinant hirudin (lepirudin) for the improvement of thrombolysis with streptokinase in patients with acute myocardial infarction: results of the HIT-4 trial. J Am Coll Cardiol. 1999 Oct;34(4):966-73. Abstract

External Links

FDA: Patient Information Sheet