Active ingredient: Argatroban - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Anticoagulants
• Anticoagulants

Dosage Forms

• Solution

Brands / Synonyms

Argatroban; Not Available

Indications

For prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia

Pharmacology

Argatroban is a synthetic direct thrombin inhibitor derived from L-arginine indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia. Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity. Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation. Argatroban is highly selective for thrombin with an inhibitory constant (K_i) of 0.04 µM. At therapeutic concentrations, Argatroban has little or no effect on related serine proteases (trypsin, factor Xa, plasmin, and kallikrein). Argatroban is capable of inhibiting the action of both free and clot-associated thrombin.

Mechanism of Action

Argatroban exerts its anticoagulant effects by inhibiting thrombin-catalyzed or -induced reactions, including fibrin formation; activation of coagulation factors V, VIII, and XIII; protein C; and platelet aggregation.

Absorption

Not Available

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Not Available

Contraindications

Argatroban is contraindicated in patients with overt major bleeding, or in patients hypersensitive to this product or any of its components.

Drug Interactions

Heparin:   Since heparin is contraindicated in patients with heparin-induced thrombocytopenia, the co-administration of Argatroban and heparin is unlikely for this indication. However, if Argatroban is to be initiated after cessation of heparin therapy, allow sufficient time for heparin's effect on the aPTT to decrease prior to initiation of Argatroban therapy.

Aspirin/Acetaminophen:   Pharmacokinetic or pharmacodynamic drug-drug interactions have not been demonstrated between Argatroban and concomitantly administered aspirin (162.5 mg orally given 26 and 2 hours prior to initiation of Argatroban 1 µg/kg/min. over 4 hours) or acetaminophen (1000 mg orally given 12, 6 and 0 hours prior to, and 6 and 12 hours subsequent to, initiation of Argatroban 1.5 µg/kg/min. over 18 hours).

Oral anticoagulant agents:   Pharmacokinetic drug-drug interactions between Argatroban and warfarin (7.5 mg single oral dose) have not been demonstrated. However, the concomitant use of Argatroban and warfarin (5-7.5 mg initial oral dose followed by 2.5-6 mg/day orally for 6-10 days) results in prolongation of the prothrombin time (PT) and International Normalized Ratio (INR).

Thrombolytic agents:   The safety and effectiveness of Argatroban with thrombolytic agents have not been established.

Co-administration:   Concomitant use of Argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of bleeding. Drug-drug interactions have not been observed between Argatroban and digoxin or erythromycin.