argatroban (Acova)

Dosing and uses of Acova (argatroban)

• Adult
• Pediatric

 

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