ARGATROBAN

ARGATROBAN (ar-ga'tro-ban) Acova, Novastan Classifications: anticoagulant; thrombin inhibitor; Therapeutic: anticoagulant; thrombin inhibitor Prototype: Lepirudin Pregnancy Category: C

Availability

250 mg/2.5 mL vials

Action

Synthetic derivative of arginine that is a direct thrombin inhibitor. Capable of inhibiting the action of both free and clot-bound thrombin.

Therapeutic Effect

Reversibly binds to the thrombin active site, thereby blocking clot-forming activity of thrombin.

Uses

Prophylaxis or treatment of thrombosis in patients with heparin-induced thrombocytopenia (HIT); prophylaxis or treatment of coronary artery thrombosis during percutaneous coronary interventions (PCI) in patients at risk for HIT.

Unlabeled Uses

Treatment of disseminated intravascular coagulation (DIC).

Contraindications

Hypersensitivity to argatroban; lactation. Any bleeding including intracranial bleeding, GI bleeding, retroperitoneal bleeding, pregnancy (category C); severe hepatic impairment.

Cautious Use

Diseased states with increased risk of hemorrhaging; severe hypertension; GI ulcerations, hepatic impairment; spinal anesthesia, stroke, surgery, trauma. Safety and effectiveness in children <18 y are not established.

Route & Dosage

Prevention & Treatment of Thrombosis Adult: IV 2 mcg/kg/min, may be adjusted to maintain an aPTT of 1.5–3 times baseline (max: 10 mcg/kg/min) Hepatic Impairment 0.5 mcg/kg/min, may be adjusted to maintain an aPTT of 1.5–3 times baseline (max: 10 mcg/kg/min) Prophylaxis or Treatment of Coronary Thrombosis during PCI Adult: IV Initiate at 25 mcg/kg/min, then bolus of 350 mcg/kg administered via a large bore IV line over 3–5 min, then 25 mcg/kg/min by continuous infusion; maintain activated clotting time (ACT) 300–450 sec; if ACT below 300 sec, increase infusion to 30 mcg/kg/min; if ACT over 450 sec, decrease infusion to 15 mcg/kg/min

Administration

Intravenous Note: Argatroban is supplied in 100 mg/mL vials which must be diluted 100-fold prior to infusion. PREPARE: Continuous: Dilute each 2.5 mL vial by mixing with 250 mL of D5W, NS, or RL to yield 1 mg/mL. Mix by repeated inversion of the diluent bag for 1 min.   ADMINISTER: Continuous for Heparin-Induced Thrombocytopenia (HIT/HITTS): Before administration, discontinue heparin and obtain a baseline aPTT. Give at a rate of 2 mcg/kg/min, or as ordered. Lower initial doses are required with hepatic impairment. Check aPTT 2 h after initiation of therapy. After the initial dose, adjust dose (not to exceed 10 mcg/kg/min) until the steady-state aPTT is 1.5 to 3 times baseline (not to exceed 100 sec). Adjust dose to maintain aPTT at 1.5–3 times baseline, but not >100 sec. Check aPTT 2 h after initiation of therapy to confirm desired therapeutic range.  Continuous for Percutaneous Coronary Intervention: Start an infusion at 25 mcg/kg/min and give a bolus of 350 mcg/kg, via a large bore IV line, over 3–5 min. Check ACT 5–10 min after the bolus dose. If the ACT is >450 sec, decrease infusion rate to 15 mcg/kg/min. If ACT is <300 sec, give an additional bolus of 150 mcg/kg and increase infusion to 30 mcg/kg/min. Check ACT q5–10min to maintain an ACT level 300–450 sec.   Diluted solutions are stable for 24 h at 25° C (77° F) in ambient indoor light. Protect from direct sunlight. Store solutions refrigerated at 2°–8° C (36°–46° F) in the dark.

Adverse Effects (≥1%)

Body as a Whole: Fever, sepsis, pain, allergic reactions (rare). CV: Hypotension, cardiac arrest, ventricular tachycardia. GI: Diarrhea, nausea, vomiting, coughing, abdominal pain. Hematologic: Major GI bleed, minor GI bleeding, hematuria, decrease Hgb/Hct, groin bleed, hemoptysis, brachial bleed. Respiratory: Dyspnea. Urogenital: UTI.

Interactions

Drug: Heparin results in increased bleeding; may prolong PT with warfarin; may increase risk of bleeding with thrombolytics. Herbal: Feverfew, garlic, ginger, ginkgo may increase potential for bleeding.

Pharmacokinetics

Peak: 1–3 h. Distribution: In extracellular fluid; 54% protein bound. Metabolism: In liver by CYP3A4/5. Elimination: Primarily in bile (78%). Half-Life: 39–51 min.

Nursing Implications

Assessment & Drug Effects

• Heparin-Induced Thrombocytopenia: Monitor aPTT. Dose adjustment may be needed to reach the target aPTT. Check aPTT 2 h after initiation of therapy. After the initial dose, adjust dose (not to exceed 10 mcg/kg/min), until the steady-state aPTT is 1.5 to 3 times baseline (not to exceed 100 sec).
• Monitor cardiovascular status carefully during therapy.
• Monitor for and report S&S of bleeding: Ecchymosis, epistaxis, GI bleeding, hematuria, hemoptysis.
• Note: Patients with history of GI ulceration, hypertension, recent trauma, or surgery are at increased risk for bleeding.
• Monitor neurologic status and report immediately focal or generalized deficits.
• Lab tests: Baseline and periodic ACT (activated clotting time), thrombin time (TT), platelet count, Hgb & Hct; daily INR when argatroban and warfarin are co-administered; periodic stool test for occult blood; urinalysis.

Patient & Family Education

• Report immediately any of the following to physician: Unexplained back or stomach pain; black, tarry stools; blood in urine, coughing up blood; difficulty breathing; dizziness or fainting spells; heavy menstrual bleeding; nosebleeds; unusual bruising or bleeding at any site.

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Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug