Argatroban

Generic Name: argatroban

Anti-coagulant [EPC]Over-the-Counter (OTC)

Brand Names:

Argatroban

11 DESCRIPTION Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 1-[5-[(aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl]amino]pentyl]-4-methyl-2-piperidinecarboxylic acid, monohydrate. Argatroban has 4 asymmetric carbons. One of the asymmetric carbons has an R configuration (stereoisomer Type I) and an S configuration (stereoi-somer Type II).

Overview

11 DESCRIPTION Argatroban is a synthetic direct thrombin inhibitor and the chemical name is 1-[5-[(aminoiminomethyl)amino]-1-oxo-2-[[(1,2,3,4-tetrahydro-3-methyl-8-quinolinyl)sulfonyl]amino]pentyl]-4-methyl-2-piperidinecarboxylic acid, monohydrate. Argatroban has 4 asymmetric carbons. One of the asymmetric carbons has an R configuration (stereoisomer Type I) and an S configuration (stereoi-somer Type II).

Uses

1 INDICATIONS AND USAGE Argatroban is a direct thrombin inhibitor indicated: • For prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT) ( 1.1 ). • As an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI) ( 1.2 ). 1.1 Heparin-Induced Thrombocytopenia Argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT). 1.2 Percutaneous Coronary Intervention Argatroban injection is indicated as an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI).

Dosage

2 DOSAGE AND ADMINISTRATION Argatroban injection must be diluted 100-fold by mixing with 0.9% Sodium Chloride Injection, 5% Dextrose Injection or Lactated Ringer’s Injection to a final concentration of 1 mg/mL prior to administration ( 2.1 ). Heparin-Induced Thrombocytopenia The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion ( 2.1 ). Percutaneous Coronary Intervention The dose for patients with or at risk for heparin-induced thrombocytopenia undergoing percutaneous coronary intervention is started at 25 mcg/kg/min and a bolus of 350 mcg/kg administered via a large bore intravenous line over 3 to 5 minutes ( 2.2 ).

Side Effects

6 ADVERSE REACTIONS The following adverse reaction is also discussed in other sections of the labeling: • Risk of Hemorrhage [see Warnings and Precautions (5.1) ] . • HIT patients: The most common (> 5%) adverse reactions were dyspnea, hypotension, fever, diarrhea, sepsis, and cardiac arrest ( 6.1 ). • PCI patients: The most common (> 5%) adverse reactions were chest pain, hypotension, back pain, nausea, vomiting and headache ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Interactions

7 DRUG INTERACTIONS • Heparin: Allow sufficient time for heparin’s effect on aPTT to decrease before initiating argatroban injection therapy ( 7.1 ). • Warfarin: Concomitant use results in increased prolongation of PT and INR ( 7.2 ). • Thrombolytic agents or glycoprotein IIb/IIIa antagonists: Safety and effectiveness of concomitant use with argatroban have not been established ( 7.4 , 7.5 ). 7.1 Heparin If argatroban is to be initiated after cessation of heparin therapy, allow sufficient time for heparin’s effect on the aPTT to decrease prior to initiation of argatroban therapy. 7.2 Oral Anticoagulant Agents Pharmacokinetic drug-drug interactions between argatroban and warfarin (7.5 mg single oral dose) have not been demonstrated.

Warnings

5 WARNINGS AND PRECAUTIONS • Risk of hemorrhage: Hemorrhage at any site can occur (unexplained fall in hematocrit or blood pressure or other unexplained symptom may indicate hemorrhage.) Use with caution in patients at risk, including those receiving antiplatelet agents, thrombolytics, or other anticoagulants. ( 5.1 ). • Use in hepatic impairment: Adjust starting dose and titrate carefully in patients with HIT who have moderate or severe hepatic impairment. Avoid use in PCI in patients with clinically significant hepatic impairment ( 5.2 ). 5.1 Risk of Hemorrhage Hemorrhage can occur at any site in the body in patients receiving argatroban. Unexplained fall in hematocrit or blood pressure may indicate hemorrhage. 4 CONTRAINDICATIONS Argatroban is contraindicated in: • Patients with major bleeding [see Warnings and Precautions (5.1) ]. • Patients with a history of hypersensitivity to argatroban. Airway, skin, and generalized hypersensitivity reactions have been reported [see Adverse Reactions (6.4) ]. • Major bleeding ( 4 ). • History of hypersensitivity to this product ( 4 ).

Pregnancy

8.1 Pregnancy Risk Summary Limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. There are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see Clinical Considerations).

Storage

16 HOW SUPPLIED/STORAGE AND HANDLING NDC 63323-526-03, 250 mg per 2.5 mL (100 mg per mL) single-dose vial, packaged individually. Storage Store the vial in original carton at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Protect from freezing. Protect from light (keep in outer carton).

Frequently Asked Questions

What is Argatroban used for?

1 INDICATIONS AND USAGE Argatroban is a direct thrombin inhibitor indicated: • For prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT) ( 1.1 ). • As an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI) ( 1.2 ). 1.1 Heparin-Induced Thrombocytopenia Argatroban injection is indicated for prophylaxis or treatment of thrombosis in adult patients with heparin-induced thrombocytopenia (HIT). 1.2 Percutaneous Coronary Intervention Argatroban injection is indicated as an anticoagulant in adult patients with or at risk for HIT undergoing percutaneous coronary intervention (PCI).

What are the side effects of Argatroban?

6 ADVERSE REACTIONS The following adverse reaction is also discussed in other sections of the labeling: • Risk of Hemorrhage [see Warnings and Precautions (5.1) ] . • HIT patients: The most common (> 5%) adverse reactions were dyspnea, hypotension, fever, diarrhea, sepsis, and cardiac arrest ( 6.1 ). • PCI patients: The most common (> 5%) adverse reactions were chest pain, hypotension, back pain, nausea, vomiting and headache ( 6.2 ). To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Can I take Argatroban during pregnancy?

8.1 Pregnancy Risk Summary Limited data from published literature and postmarketing reports do not suggest an association between argatroban and adverse fetal developmental outcomes. There are risks to the mother associated with untreated thrombosis in pregnancy and a risk of hemorrhage in the mother and fetus associated with use of anticoagulants (see Clinical Considerations).

What are the important warnings for Argatroban?

5 WARNINGS AND PRECAUTIONS • Risk of hemorrhage: Hemorrhage at any site can occur (unexplained fall in hematocrit or blood pressure or other unexplained symptom may indicate hemorrhage.) Use with caution in patients at risk, including those receiving antiplatelet agents, thrombolytics, or other anticoagulants. ( 5.1 ). • Use in hepatic impairment: Adjust starting dose and titrate carefully in patients with HIT who have moderate or severe hepatic impairment. Avoid use in PCI in patients with clinically significant hepatic impairment ( 5.2 ). 5.1 Risk of Hemorrhage Hemorrhage can occur at any site in the body in patients receiving argatroban. Unexplained fall in hematocrit or blood pressure may indicate hemorrhage. 4 CONTRAINDICATIONS Argatroban is contraindicated in: • Patients with major bleeding [see Warnings and Precautions (5.1) ]. • Patients with a history of hypersensitivity to argatroban. Airway, skin, and generalized hypersensitivity reactions have been reported [see Adverse Reactions (6.4) ]. • Major bleeding ( 4 ). • History of hypersensitivity to this product ( 4 ).

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Medical Disclaimer

This drug information is for educational purposes only and should not replace professional medical advice. Drug information is sourced from the FDA National Drug Code Directory and Structured Product Labeling. Always consult with a healthcare provider before starting, stopping, or changing any medication.