argatroban

ar-GAT-tro-ban

Therapeutic Classification: anticoagulants

Pharmacologic Classification: thrombin inhibitors

High Alert

Prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT).
As an anticoagulant in patients with or at risk for heparin-induced thrombocytopenia who are undergoing percutaneous coronary intervention (PCI).

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).

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/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 (↑ in hepatic impairment).

(anticoagulant effect)

ROUTE	ONSET	PEAK	DURATION
IV	immediate	1–3 hr	2–4 hr

Contraindicated in:

Major bleeding;
Hypersensitivity.

Use Cautiously in:

Hepatic impairment (↓ initial infusion rate recommended);
OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
Pedi: Safety and effectiveness not established in children.

CV: hypotension

GI: diarrhea, nausea, vomiting

Hemat: BLEEDING

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Drug-drug:

Risk of bleeding may be ↑ by concurrent use of antiplatelet agents, thrombolytic agents, or other anticoagulants.

Drug-Natural Products:

↑bleeding risk with anise, arnica, chamomile, clove, feverfew, garlic, ginger, ginkgo, Panax ginseng, and others.

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 and ↑ infusion rate to 30 mcg/kg/min. If ACT is >450 sec infusion rate should be ↓ to 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 rate ↑ to 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.

(Generic available)

Premixed infusion: 50 mg/50 mL
Solution for injection: 100 mg/mL

Monitor vital signs periodically during therapy. Unexplained decreases in BP may indicate hemorrhage. Assess patient for bleeding. Minimize arterial and venous punctures, IM injections, and use of urinary catheters, nasotracheal intubation, and nasogastric tubes. Avoid noncompressible sites for IV access. Monitor for blood in urine, lower back pain, pain or burning on urination. If bleeding cannot be controlled with pressure, decrease dose or discontinue argatroban immediately.
Monitor for signs of anaphylaxis (rash, coughing, dyspnea) during therapy.

Lab Test Considerations:

Monitor aPTT prior to initiation of continuous infusion, 2 hrs after initiation of therapy, and periodically during therapy to confirm aPTT is within desired therapeutic range.
- For patients undergoing PCI, monitor ACT as described in Route and Dose section.
- Assess hemoglobin, hematocrit, and platelet count prior to, and periodically during, argatroban therapy. May cause ↓ hemoglobin and hematocrit. Unexplained ↓ hematocrit may indicate hemorrhage.
- Use of argatroban concurrently with multiple doses of warfarin will result in more prolonged prothrombin time and international normalized ratio (INR) (although there is not an ↑ in vitamin K-dependent factor X_a activity) than when warfarin is used alone. Monitor INR daily during concomitant therapy. Repeat INR 4–6 hr after argatroban is discontinued. If repeat value is below desired therapeutic value for warfarin alone, restart argatroban therapy and continue until desired therapeutic range for warfarin alone is reached. To obtain the INR for warfarin alone when dose of argatroban is >2 mcg/kg/min, temporarily reduce argatroban dose to 2 mcg/kg/min; INR for combined therapy may then be obtained 4–6 hr after argatroban dose was reduced.

Toxicity and Overdose:

There is no specific antidote for argatroban. If overdose occurs, discontinue argatroban. Anticoagulation parameters usually return to baseline within 2–4 hr after discontinuation.

Do not confuse argatroban with Aggrastat.
Discontinue all parenteral anticoagulants before argatroban therapy is started. Oral anticoagulation may be initiated with maintenance dose of warfarin; do not administer loading dose. Discontinue argatroban therapy when INR for combined therapy is >4.

IV Administration:

IV: Do not administer solutions that are cloudy or contain particulate matter. Discard unused portion.
Diluent: Bolus dose of 350 mcg/kg should be given prior to continuous infusion in patients undergoing PCI. For Diluent information, see Continuous Infusion section below.
Diluent: Dilute each 100 mg/mL in 250 mL of 0.9% NaCl, D5W, or LR.1 mg/mL. Mix by repeated inversion for 1 min. Diluted solution is slightly viscous, clear, and colorless to pale yellow; may show a slight haziness that disappears upon mixing; solution must be clear before use. Solution is stable at controlled room temperature and ambient light for 24 hrs, or for 96 hrs at controlled room temperature or refrigerated and protected from light; do not expose to direct sunlight. Pre-mixed solutions are clear and colorless. Store at room temperature, do not refrigerate or freeze.

Explain the purpose of argatroban to patient.
Advise patient to avoid other products known to affect bleeding.
Instruct patient to notify health care professional immediately if any bleeding or signs and symptoms of allergic reaction is noted.
Rep: Advise females or reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Decreased thrombus formation and extension.
- Decreased sequelae of thrombosis (emboli, post-phlebitic syndromes).

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆