Lepirudin

Lepirudin Brand Name– Refludan

What is Lepirudin

Lepirudin is a yeast-derived recombinant form of the natural anticoagulant hirudin. Natural hirudin is a 65 amino acid compound produced in trace amounts by the European medicinal leech.

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.

Lepirudin is the first drug approved in the US for anticoagulation in patients with heparin-induced thrombocytopenia (HIT).

Lepirudin has been shown to substantially reduce the risk of serious new thromboembolic complications in patients with HIT.

Lepirudin was FDA approved for the management of HIT in March of 1998. The manufacturer filed for a NDA for unstable angina and acute coronary syndromes in 1999; the FDA issued a non-approvable letter for this indication in May 2000.

The ACCP antithrombotic guidelines recommend against the use direct thrombin inhibitors (e.g., lepirudin) for routine initial antithrombotic treatment of acute coronary syndrome (ACS) associated with unstable angina (UA) or non-ST segment elevation myocardial infarction (NSTEMI).

This recommendation is based on limitations of clinical trials of direct thrombin inhibitors in ACS and the complexity of use of these agents relative to alternative antithrombotics such as unfractionated heparin and low-molecular-weight heparin

Indications

  1. acute myocardial infarction
  2. heparin-induced thrombocytopenia
  3. thrombosis prophylaxis
  4. unstable angina

For anticoagulation for thrombosis prophylaxis in patients with heparin-induced thrombocytopenia (HIT)

NOTE: Lepirudin has been designated an orphan drug by the FDA for the treatment of HIT and associated thromboembolic disease to prevent further thromboembolic complications.

NOTE: The American College of Chest Physicians (ACCP) recommends the same management approach for HIT-associated thrombosis and isolated HIT.

Side Effects

  1. anaphylactic shock
  2. anaphylactoid reactions
  3. anemia
  4. angioedema
  5. bleeding
  6. bronchospasm
  7. chills
  8. cough
  9. dyspnea
  10. edema
  11. epistaxis
  12. fever
  13. flushing
  14. GI bleeding
  15. heart failure
  16. hematoma
  17. hematuria
  18. hemoptysis
  19. infection
  20. intracranial bleeding
  21. laryngeal edema
  22. pruritus
  23. rash
  24. retroperitoneal bleeding
  25. urticaria
  26. vaginal bleeding

Monitoring Parameters

  • hemoglobin/hematocrit
  • partial thromboplastin time (PTT)
  • platelet count
  • serum creatinine
  • stool guaiac
  • urinalysis

Contraindications

  • aneurysm
  • bleeding
  • breast-feeding
  • children
  • coagulopathy
  • diverticulitis
  • endocarditis
  • GI bleeding
  • hemophilia
  • hepatic disease
  • hypertension
  • infants
  • inflammatory bowel disease
  • intracranial bleeding
  • intramuscular injections
  • labor
  • lumbar puncture
  • menstruation
  • neonates
  • obstetric delivery
  • peptic ulcer disease
  • pregnancy
  • renal disease
  • renal impairment
  • retroperitoneal bleeding
  • spinal anesthesia
  • stroke
  • surgery
  • thrombolytic therapy

Interactions

  • Abciximab
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Ado-Trastuzumab emtansine
  • Altretamine
  • Aminosalicylate sodium, Aminosalicylic acid
  • Amlodipine; Celecoxib
  • Anagrelide
  • Antithrombin III
  • Antithymocyte Globulin
  • Apixaban
  • Argatroban
  • Arsenic Trioxide
  • Aspirin, ASA
  • Aspirin, ASA; Butalbital; Caffeine
  • Aspirin, ASA; Butalbital; Caffeine; Codeine
  • Aspirin, ASA; Caffeine; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Aspirin, ASA; Carisoprodol
  • Aspirin, ASA; Carisoprodol; Codeine
  • Aspirin, ASA; Citric Acid; Sodium Bicarbonate
  • Aspirin, ASA; Dipyridamole
  • Aspirin, ASA; Omeprazole
  • Aspirin, ASA; Oxycodone
  • Aspirin, ASA; Pravastatin
  • Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate
  • Betrixaban
  • Bismuth Subsalicylate
  • Bismuth Subsalicylate; Metronidazole; Tetracycline
  • Bivalirudin
  • Caplacizumab
  • Carbenicillin
  • Celecoxib
  • Chlorambucil
  • Choline Salicylate; Magnesium Salicylate
  • Cilostazol
  • Citalopram
  • Clofarabine
  • Clopidogrel
  • Collagenase
  • Cytarabine, ARA-C
  • Dabigatran
  • Dalteparin
  • Dasatinib
  • Decitabine
  • Deferasirox
  • Defibrotide
  • Denileukin Diftitox
  • Desirudin
  • Dextran
  • Diclofenac
  • Diclofenac; Misoprostol
  • Diflunisal
  • Diphenhydramine; Ibuprofen
  • Diphenhydramine; Naproxen
  • Dipyridamole
  • Drotrecogin Alfa
  • Edoxaban
  • Eltrombopag
  • Enoxaparin
  • Epoprostenol
  • Eptifibatide
  • Escitalopram
  • Esomeprazole; Naproxen
  • Esterified Estrogens; Methyltestosterone
  • Estramustine
  • Etodolac
  • Famotidine; Ibuprofen
  • Fenoprofen
  • Fish Oil, Omega-3 Fatty Acids (Dietary Supplements)
  • Floxuridine
  • Fluorouracil, 5-FU
  • Fluoxetine
  • Fluoxetine; Olanzapine
  • Flurbiprofen
  • Fluvoxamine
  • Folate analogs
  • Fondaparinux
  • Garlic, Allium sativum
  • Ginger, Zingiber officinale
  • Ginkgo, Ginkgo biloba
  • Green Tea
  • Hemin
  • Heparin
  • Hydrocodone; Ibuprofen
  • Hydroxyurea
  • Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate
  • Ibritumomab Tiuxetan
  • Ibrutinib
  • Ibuprofen
  • Ibuprofen; Oxycodone
  • Ibuprofen; Pseudoephedrine
  • Icosapent ethyl
  • Iloprost
  • Indomethacin
  • Inotersen
  • Interferon Alfa-2a
  • Interferon Alfa-2b
  • Interferon Alfa-2b; Ribavirin
  • Interferon Alfa-n3
  • Interferon Alfacon-1
  • Intravenous Lipid Emulsions
  • Ketoprofen
  • Ketorolac
  • Lansoprazole; Naproxen
  • Lomustine, CCNU
  • Magnesium Salicylate
  • Meclofenamate Sodium
  • Mefenamic Acid
  • Meloxicam
  • Methoxsalen
  • Methylsulfonylmethane, MSM
  • Methyltestosterone
  • Mifepristone
  • Miltefosine
  • Mycophenolate
  • Nabumetone
  • Nandrolone Decanoate
  • Naproxen
  • Naproxen; Pseudoephedrine
  • Naproxen; Sumatriptan
  • Natural Antineoplastics
  • Nelarabine
  • Nintedanib
  • Nonsteroidal antiinflammatory drugs
  • Obinutuzumab
  • Omacetaxine
  • Oxandrolone
  • Oxaprozin
  • Paroxetine
  • Pentosan
  • Phentermine; Topiramate
  • Piperacillin
  • Piperacillin; Tazobactam
  • Piroxicam
  • Platelet Inhibitors
  • Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements)
  • Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved)
  • Prasugrel
  • Rivaroxaban
  • Rofecoxib
  • Salicylates
  • Salsalate
  • Selective serotonin reuptake inhibitors
  • Serotonin norepinephrine reuptake inhibitors
  • Sertraline
  • Sodium Iodide
  • Sulfinpyrazone
  • Sulindac
  • Telavancin
  • Thrombolytic Agents
  • Ticagrelor
  • Ticarcillin
  • Ticarcillin; Clavulanic Acid
  • Ticlopidine
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  • Trazodone
  • Treprostinil
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  • Warfarin