argatroban

 Indications

Prophylaxis or treatment of thrombosis in patients with

heparin-induced thrombocytopenia. As an anticoagulant

in patients with or at risk for heparin-induced

thrombocytopenia who are undergoing percutaneous

coronary intervention (PCI).

Action

Inhibits thrombin by binding to its receptor sites. Inhibition

of thrombin prevents activation of factors V, VIII,

and XII; the conversion of fibrinogen to fibrin; platelet

adhesion and aggregation. Therapeutic Effects:

Decreased thrombus formation and extension with decreased

sequelae of thrombosis (emboli, postphlebitic

syndromes). 

Pharmacokinetics A

Absorption: IV administration results in complete

bioavailability.

Distribution: Unknown.

Metabolism and Excretion: Mostly metabolized

by the liver; excreted primarily in feces via biliary excretion.

16% excreted unchanged in urine, 14% excreted

unchanged in feces.

Half-life: 39–51 min (qin hepatic impairment).

TIME/ACTION PROFILE (anticoagulant effect)

ROUTE ONSET PEAK DURATION

IV immediate 1–3 hr 2–4 hr

Contraindications/Precautions

Contraindicated in: Major bleeding; Hypersensitivity;

Lactation: Lactation.

Use Cautiously in: Hepatic impairment (pinitial

infusion rate recommended); OB: Use only if clearly

needed; Pedi: Safety not established.

Adverse Reactions/Side Effects

CV: hypotension. GI: diarrhea, nausea, vomiting. Hemat:

BLEEDING. Misc: allergic reactions including ANAPHYLAXIS,

fever.

Interactions

Drug-Drug: Risk of bleeding may beqby concurrent

use of antiplatelet agents, thrombolytic

agents, or other anticoagulants.

Drug-Natural Products:qbleeding risk with anise,

arnica, chamomile, clove, feverfew, garlic,

ginger, ginkgo, Panax ginseng, and others.

Route/Dosage

IV (Adults): 2 mcg/kg/min as a continuous infusion;

adjust infusion rate on the basis of activated partial

thromboplastin time (aPTT). Patients undergoing

PCI—350 mcg/kg bolus followed by infusion at 25

mcg/kg/min, activated clotting time (ACT) should be

assessed 5–10 min later. If ACT is 300–450 sec, procedure

may be started. If ACT 300 sec, give additional

bolus of 150 mcg/kg andqinfusion rate to 30 mcg/kg/

min. If ACT is 450 sec infusion rate should bepto 15

mcg/kg/min and ACT rechecked after 5–10 min. If

thrombotic complications occur or ACT drops to 300

sec, an additional bolus of 150 mcg/kg may be given

and the infusion rateqto 40 mcg/kg/min followed by

ACT monitoring. If anticoagulation is required after surgery,

lower infusion rates should be used.

Hepatic Impairment

IV (Adults): 0.5 mcg/kg/min as a continuous infusion;

adjust infusion rate on the basis of aPTT.

Availability (generic available)

Solution for injection: 100 mg/mL. Premixed infusion:

50 mg/50 mL, 125 mg/125 mL, 250 mg/250 mL.