Argatroban for prevention and treatment of thromboembolism in heparin-induced thrombocytopenia.
OBJECTIVE
To renew the pharmacology, pharmacokinetics, efficacy adverse events, and cost of argatroban in the prevention and treatment of thromboembolism in patients with heparin-induced thrombocytopenia (HIT).


METHODS
A MEDLINE search (1980 to August 2000) of English-language literature was conducted using the search term argatroban to identify pertinent case reports, clinical trials, abstracts, and review articles. Additional reports were identified from the reference lists compiled in the literature reviewed, as well as from the manufacturer.


RESULTS
Argatroban is a synthetic direct thrombin inhibitor indicated for parenteral use in the prevention and treatment of thromboembolism in patients with HIT. Its elimination half-life is approximately 40-50 minutes, and it is primarily eliminated by hepatic metabolism and biliary secretion. Compared with historical controls, argatroban-treated patients with HIT or HIT with thrombosis (HITTS) experienced lower rates of the composite end point of death, amputation, and new thrombosis. Dosing is initiated at 2 microg/kg/min and adjusted to maintain the activated partial thromboplastin time at 1.5-3 times the patient's baseline. In Japan, argatroban is approved for use in acute ischemic stroke and chronic peripheral occlusive disease. It has also been used as an alternative to unfractionated heparin (UFH) in patients with a history of HIT or HITTS undergoing percutaneous coronary intervention and other procedures. Additionally, argatroban has been compared with UFH in patients with acute myocardial infarction who were receiving thrombolytic therapy. Hemorrhage is the primary adverse event associated with argatroban. Argatroban increases the prothrombin time, making assessment of the intensity of warfarin therapy during concurrent administration more complex.


CONCLUSIONS
The use of argatroban in patients with HIT and HITTS is associated with improvement in clinical outcomes compared with historical controls. Argatroban offers several practical advantages over other available agents with respect to dosing, monitoring, reversibility of effect with discontinuation of the drug, and cost.
Kondo
L M
LM
School of Pharmacy, University of Washington, Seattle, USA.
Wittkowsky
A K
AK
Wiggins
B S
BS
D000818:Animals; D000925:Anticoagulants / Q000009:adverse effects*; D000991:Antithrombins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D001120:Arginine / Q000031:analogs & derivatives; D002986:Clinical Trials as Topic; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D010875:Pipecolic Acids / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013449:Sulfonamides; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000188:drug therapy*; D013923:Thromboembolism / Q000188:drug therapy*
D000925:Anticoagulants; D000991:Antithrombins; D010875:Pipecolic Acids; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban