|
| Primary information |
|---|
| ID | 10001 |
| Therapeutic ID | Th1001 |
| Protein Name | Lepirudin |
| Sequence | >Th1001_Lepirudin
LTYTDCTESGQNLCLCEGSNVCGQGNKCILGSDGEKNQCVTGEGTPKPQSHNDGDFEEIPEEYLQ
|
| Molecular Weight | 6979 |
| Chemical Formula | C287H440N80O111S6 |
| Isoelectric Point | 3.7 |
| Hydrophobicity | -0.777 |
| Melting point | 65 |
| Half-life | Approximately 1.3 hours |
| Description | Lepirudin is identical to natural hirudin except for substitution of leucine for isoleucine at the N-terminal end of the molecule and the absence of a sulfate group on the tyrosine at position 63. It is produced via yeast cells. |
| Indication/Disease | For the treatment of heparin-induced thrombocytopenia. |
| Pharmacodynamics | Lepirudin is used to break up clots and to reduce thrombocytopenia. It binds to thrombin and prevents thrombus or clot formation. It is a highly potent, selective, and essentially irreversible inhibitor of thrombin and clot-bond thrombin. Lepirudin requires no cofactor for its anticoagulant action. Lepirudin is a recombinant form of hirudin, an endogenous anticoagulant found in medicinal leeches. |
| Mechanism of Action | Lepirudin forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen and initiate the clotting cascade. The inhibition of thrombin prevents the blood clotting cascade. |
| Toxicity | In case of overdose (eg, suggested by excessively high aPTT values) the risk of bleeding is increased. |
| Metabolism | Lepirudin is thought to be metabolized by release of amino acids via catabolic hydrolysis of the parent drug. However, conclusive data are not available. About 48% of the administration dose is excreted in the urine which consists of unchanged drug (35%) |
| Absorption | Bioavailability is 100% following injection. |
| 12.2 L [Healthy young subjects (n = 18, age 18-60 years)] |
| Clearance | 164 ml/min [Healthy 18-60 yrs] |
| Categories | Amino Acids, Peptides, and Proteins, Anticoagulants, Antithrombin Proteins, Antithrombins, Blood and Blood Forming Organs, Cardiovascular Agents, Enzyme Inhibitors, Fibrin Modulating Agents, Hematologic Agents, Peptides, Protease Inhibitors, Proteins, Serine Protease Inhibitors, Serpins, Thrombin Inhibitors |
| Patents Number | CA1339104 |
| Date of Issue | 29-Jul-1997 |
| Date of Expiry | 29-Jul-2014 |
| Drug Interaction | Ginkgo biloba = may increase bleed risk. |
| Target | Prothrombin |
| Brand Name | Refludan |
| Company | Berlex Labs |
| Brand Description | Berlex Labs |
| Prescribed For | heparin-induced thrombocytopenia (HIT) and associated thromboembolic disease |
| Chemical Name | [Leu1, Thr2]-63-desulfohirudin |
| Formulation | Each vial of REFLUDAN contains 50 mg lepirudin. Other ingre-dients are 40 mg mannitol and sodium hydroxide for adjust-ment of pH to approximately 7 |
| Physical Appearance | Sterile, white, freeze-dried powder |
| Route of Administration | Intravenous infusion |
| Recommended Dosage | Recommended dose is 0.4 mg/kg body weight (up to 110kg) slowly intravenously (eg, over 15 to 20seconds) as a bolus dose, and can be followed by 0.15 mg/kg body weight (up to 110kg)/hour as a continuous Intravenous infusion for 2 to 10 days or longer if CL. |
| Contraindication | Hypersensitivity |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |