Argatroban

Indications

Argatroban is used for: Thrombocytopenia, Percutaneous Coronary Intervention

Adult Dose

Intravenous Thrombocytopenia Indicated as an anticoagulant for prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia Initial: 2 mcg/kg/min IV continuous infusion over 1-3 hours until steady-state aPTT is 1.5-3 times initial baseline value Not to exceed infusion rate of 10 mcg/kg/min Check aPTT and adjust dose until target aPTT is achieved Percutaneous Coronary Intervention Indicated as an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention (PCI) Initial: 25 mcg/kg/min IV infusion, AND A bolus of 350 mcg/kg IV over 3-5 minutes via large-bore IV line Check activated clotting time (ACT) 5-10 minutes after bolus dose is completed; procedure may proceed if ACT is >300 seconds If ACT is <300 seconds, administer additional IV bolus dose of 150 mcg/kg, increase infusion dose to 30 mcg/kg/min, and check ACT 5-10 minutes later If ACT >450 seconds, decrease infusion rate to 15 mcg/kg/min, and check ACT 5-10 minutes later After therapeutic ACT (300-450 sec) achieved, continue this infusion dose for duration of procedure Hepatic impairment Approximately 4-fold decrease in clearance relative to those with normal hepatic function, so dosing modification warranted; monitor aPTT and adjust dosage as clinically indicated Thrombocytopenia: Decrease initial dose to 0.5 mcg/kg/min IV PCI: For patients with hepatic impairment undergoing PCI and who have HIT or are at risk for HIT, carefully titrate argatroban until desired level of anticoagulation achieved; use of drug in PCI patients with clinically significant hepatic disease or AST/ALT levels ?3 times the upper limit of normal should be avoided

Child Dose

Renal Dose

Administration

IV Preparation 100 mg/mL injectable, dilute to final concentration of 1 mg/mL in NS, D5W, or LR Ready-to-use preparations (1 mg/mL) require no further dilution; vial may be inverted for use with an infusion set IV Administration See adult dosing for infusion rate

Contra Indications

Active major bleeding. Severe hepatic impairment.

Precautions

Disease states and other circumstances in which there is an increased risk of haemorrhage (e.g. severe HTN, major surgery). Critically ill patients. Moderate hepatic impairment. Childn. Pregnancy and lactation. Monitoring Parameters Monitor Hb, haematocrit, signs/symptoms of bleeding; aPTT, ACT.

Pregnancy-Lactation

Pregnancy Limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes; there are risks to mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in mother and fetus associated with use of anticoagulants Pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high risk pregnancy conditions; published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy Use of anticoagulants, including argatroban, may increase risk of bleeding in fetus and neonate; monitor neonates for bleeding Pregnant women should be carefully monitored for evidence of excessive bleeding or unexpected changes in coagulation parameters during labor or delivery Lactation There are no data on presence in human milk, or effects on milk production; it is present in rat milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition There are no data on presence in human milk, or effects on milk production; it is present in rat milk; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

Interactions

Increased risk of bleeding w/ antiplatelet agents, thrombolytics and other anticoagulants. Increased INR and prothrombin time w/ warfarin.

Adverse Effects

Side effects of Argatroban : >10% GI bleeding (14%) Hematuria (12%) 1-10% Chest pain (1-15%) Hemoglobin and hematocrit decrease (10%) Hypotension (7-10%) Dyspnea (8%) Fever (7%) Sepsis (6%) Cardiac arrest (6%) Diarrhea (6%) Nausea (5%) Groin hemorrhage (5%) Pain (5%) Urinary tract infection (5%) Ventricular tachycardia (5%) Bradyarrhythmia (4.5%) Infection (4%) Vomiting (2.6-4%) Intracranial hemorrhage (1-4%) Myocardial infarction (3.5%) Hemoptysis (3%) Nephrotoxicity (3%) Cough (3%) Atrial fibrillation (3%) Brachial hemorrhage (2%) Major GI hemorrhage (1-2%) Angina (1.8%) Coronary arterial hemorrhage (1.8%) Coronary artery thrombosis (1.8%)

Mechanism of Action

Argatroban is a synthetic direct thrombin inhibitor which reversibly binds to the active thrombin site of free and clot-associated thrombin. It exerts its anticoagulant effects by inhibiting thrombin-catalysed or -induced reactions, e.g. fibrin formation; activation of coagulation factors V, VIII, and XIII; activation of protein C; and platelet aggregation.