argatroban (Acova)
Classes: Anticoagulants, Cardiovascular; Anticoagulants, Hematologic; Thrombin Inhibitors
Dosing and uses of Acova (argatroban)
Adult dosage forms and strengths
injectable solution
- 100mg/mL
ready-to-use injectable
- 50mg/50mL 0.9% NaCl
- 125mg/125mL 0.9% NaCl
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
Dosing considerations
- 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
Dosing Modifications
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: Avoid use in patients with clinically significant hepatic disease or AST/ALT levels >3 x ULN
Pediatric dosage forms and strengths
Safety and efficacy not established
Acova (argatroban) adverse (side) effects
>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%)
Frequency not defined
Minor hematuria
Pulmonary edema
Warnings
Contraindications
Hypersensitivity
Active major bleeding
Cautions
Monitor therapy with aPTt
Hemorrhagic diathesis, conditions that increase hemorrhage risk (eg, severe hypertension, major surgery, GI ulceration); unexplained fall in hematocrit or blood pressure may indicate hemorrhage
Hepatic dysfunction
Patients with illnesses that reduce clearance may require dose reduction
Safety and efficacy of concomitant administration with thrombolytic agents not established
Discontinue parenteral anticoagulant therapy prior to initiating treatment
Pregnancy and lactation
Pregnancy category: B
Lactation: Unknown whether excreted in human breast milk; administer only if benefits greatly outweigh risks
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Acova (argatroban)
Mechanism of action
Competitive, direct thrombin inhibitor that reversibly binds to thrombin active site; thrombin enables fibrinogen conversion to fibrin during the coagulation cascade
Distribution
Protein bound: 54%
Vd: 174 mL/kg
Metabolism
Liver
Elimination
Half-life: 39-51 min
Total body clearance: 5.1 mL/kg/min
Excretion: Feces (65%); urine (22%)
Administration
IV Compatibilities
Y-site
- Atropine
- Diltiazem
- Diphenhydramine
- Dobutamine
- Dopamine
- Fentanyl
- Hydrocortisone succinate
- Metoprolol
- Midazolam
- Morphine sulfate
- Norepinephrine
- Phenylephrine
- Verapamil
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