Overview
11 DESCRIPTION Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 1-[5-[(aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8- quinolinyl)sulfonyl]amino]pentyl]-4-methyl-2-piperidinecarboxylic acid, monohydrate. Argatroban has 4 asymmetric carbons.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action 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; activation of protein C; and platelet aggregation. Argatroban inhibits thrombin with an inhibition constant (Ki) 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. 12.
Indications
- 1 INDICATIONS AND USAGE Argatroban is a direct thrombin inhibitor indicated: For prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT) ( 1.1 ) As an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI) ( 1.2 ) 1.1 Heparin-Induced Thrombocytopenia Argatroban Injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT). 1.
Common Doses
- 250 mg
- 2.5 mL
- 100 mg
- 1 mg
Dosage
2 DOSAGE AND ADMINISTRATION Argatroban Injection 250 mg/2.5 mL (100 mg/mL) must be diluted 100-fold by mixing with 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL. ( 2.1 ) Argatroban Injection 50 mg/50 mL (1 mg/mL) is ready for intravenous infusion. Dilution is not required. ( 2.1 ) Heparin-Induced Thrombocytopenia The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Argatroban is contraindicated in: Patients with major bleeding, [see Warnings and Precautions (5.1) ] Patients with a history of hypersensitivity to argatroban. Airway, skin, and generalized hypersensitivity reactions have been reported [see Adverse Reactions (6.1) ] Major bleeding (4) History of hypersensitivity to this product (4)
Side Effects
- 6 ADVERSE REACTIONS The following adverse reaction is also discussed in other sections of the labeling: Risk of Hemorrhage [see Warnings and Precautions (5.1) ] . HIT patients: The most common (>5%) adverse reactions were dyspnea, hypotension, fever, diarrhea, sepsis, and cardiac arrest. (6.1) PCI patients: The most common (>5%) adverse reactions were chest pain, hypotension, back pain, nausea, vomiting and headache. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.
Interactions
- 7 DRUG INTERACTIONS Heparin: Allow sufficient time for heparin’s effect on activated partial thromboplastin time (aPTT) to decrease before initiating Argatroban Injection therapy. ( 7.1 ) Warfarin: Concomitant use results in increased prolongation of PT and INR. ( 7.2 ) Thrombolytic agents or glycoprotein IIb/IIIa antagonists: Safety and effectiveness of concomitant use with argatroban have not been established. ( 7.4 , 7.5 ) 7.