Argatroban

Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity.

• 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).

• Argatroban is contraindicated in: Patients with major bleeding, [see Warnings and Precautions (5.1) ] Patients with a history of hypersensitivity to argatroban.contraindicated

Argatroban Injection 250 mg/2.5 mL (100 mg/mL) 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. ( 2.1 ) Argatroban Injection 50 mg/50 mL (1 mg/mL) is ready for intravenous infusion. Dilution is not required. ( 2.1 ) Heparin-Induced Thrombocytopenia The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion. ( 2.2 ) 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. ( 2.3 ) 2.1 Preparation for Intravenous Administration Argatroban Injection 250 mg/2.5 mL (100 mg/mL) must be diluted 100-fold prior to infusion. Argatroban should not be mixed with other drugs prior to dilution. Dilution is not required for Argatroban Injection 50 mg/50 mL (1 mg/mL). Argatroban Injection 250 mg/2.5 mL (100 mg/mL) Argatroban 250 mg/2.5 mL (100 mg/mL) should be diluted in 0.9% Sodium Chloride Injection, 5% Dextrose Injection, or Lactated Ringer’s Injection to a final concentration of 1 mg/mL. The contents of each 2.5-mL vial should be diluted 100-fold by mixing with 250 mL of diluent. Use 250 mg (2.5 mL) per 250 mL of diluent or 500 mg (5 mL) per 500 mL of diluent. The constituted solution must be mixed by repeated inversion of the diluent bag for 1 minute.

Hemorrhage can occur. Unexplained fall in hematocrit or blood pressure may indicate hemorrhage. ( 5.1 ) 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. Intracranial and retroperitoneal hemorrhage [ see Adverse Reactions (6.1 )] have been reported. The risk of hemorrhage with argatroban may be increased in severe hypertension; immediately following lumbar puncture, spinal anesthesia, major surgery (especially involving the brain, spinal cord, or eye), hematologic conditions associated with increased bleeding tendencies such as congenital or acquired bleeding disorders, and gastrointestinal lesions such as ulcerations. Concomitant use of argatroban with antiplatelet agents, thrombolytics, and other anticoagulants may increase the risk of bleeding. 5.2 Use in Hepatic Impairment When administering argatroban to patients with hepatic impairment, start with a lower dose and carefully titrate until the desired level of anticoagulation is achieved. Achievement of steady state aPTT levels may take longer and require more argatroban dose adjustments in patients with hepatic impairment compared to patients with normal hepatic function [see Use in Specific Populations (8.6) ] .

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. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-233-2001 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Adverse Reactions in Patients with HIT (With or Without Thrombosis) Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The following safety information is based on all 568 patients treated with argatroban in Study 1 and Study 2. The safety profile of the patients from these studies is compared with that of 193 historical controls in which the adverse reactions were collected retrospectively. Adverse reactions are separated into hemorrhagic and non-hemorrhagic reactions. Major bleeding was defined as bleeding that was overt and associated with a hemoglobin decrease ≥ 2 g/dL, that led to a transfusion of ≥ 2 units, or that was intracranial, retroperitoneal, or into a major prosthetic joint. Minor bleeding was overt bleeding that did not meet the criteria for major bleeding.

Lactation: Discontinue nursing or drug, taking into account the importance of the drug to the mother. (8.2) Pediatric Use: Safety and effectiveness have not been established. (8.4) 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 ) . In animal reproduction studies, there was no evidence of adverse developmental outcomes with intravenous administration of argatroban during organogenesis in rats and rabbits at doses up to 0.3- and 0.2-times, respectively, the maximum recommended human dose (MHRD) (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively.

Metabolism

Distribution Argatroban distributes mainly in the extracellular fluid as evidenced by an apparent steady-state volume of distribution of 174 mL/kg (12.18 L in a 70 kg adult). Argatroban is 54% bound to human serum proteins, with binding to albumin and α 1 -acid glycoprotein being 20% and 34%, respectively.

Excessive anticoagulation, with or without bleeding, may be controlled by discontinuing argatroban or by decreasing the argatroban dose. In clinical studies, anticoagulation parameters generally returned from therapeutic levels to baseline within 2 to 4 hours after discontinuation of the drug. Reversal of anticoagulant effect may take longer in patients with hepatic impairment. No specific antidote to argatroban is available; if life-threatening bleeding occurs and excessive plasma levels of argatroban are suspected, discontinue argatroban immediately and measure aPTT and other coagulation parameters. When argatroban was administered as a continuous infusion (2 mcg/kg/min) prior to and during a 4-hour hemodialysis session, approximately 20% of argatroban was cleared through dialysis. Single intravenous doses of argatroban at 200, 124, 150, and 200 mg/kg were lethal to mice, rats, rabbits, and dogs, respectively. The symptoms of acute toxicity were loss of righting reflex, tremors, clonic convulsions, paralysis of hind limbs, and coma. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.

• May 9, 2011NDANDA022485Plano Pharms
• Jan 5, 2012NDANDA203049Hikma Pharm Co Ltd
• Jun 30, 2014ANDAANDA202626Mylan Institutional
• Jun 30, 2014ANDAANDA091665Ph Health
• Mar 23, 2015NDANDA201811Fresenius Kabi Usa
• May 22, 2017ANDAANDA205570Gland
• Nov 27, 2018NDANDA209552Eugia Pharma Speclts
• Jun 7, 2021NDANDA212035Accord Hlthcare

1. 1Heparin-induced Thrombocytopenia18713%
2. 2Drug Ineffective15410%
3. 3International Normalised Ratio Increased1107.4%
4. 4Off Label Use996.7%
5. 5Activated Partial Thromboplastin Time Prolonged835.6%
6. 6Haemorrhage775.2%
7. 7Pulmonary Embolism694.7%
8. 8Thrombocytopenia694.7%
9. 9Deep Vein Thrombosis684.6%
10. 10Coagulation Time Prolonged644.3%
11. 11Thrombosis563.8%
12. 12Gastrointestinal Haemorrhage523.5%
13. 13Cerebral Infarction503.4%
14. 14Platelet Count Decreased392.6%
15. 15Cerebral Haemorrhage382.6%

The 10 most recently updated of 38 ClinicalTrials.gov registrations naming Argatroban as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Safety and Efficacy of Low-dose Anticoagulation With Argatroban and Enoxaparin on ECMO
  Not yet recruiting · Phase 2 · Interventional · 200 enrolled · University Hospital Ostrava
  NCT07499037updated 2026-04-02
• Clinical Management of Argatroban in Patients With Heparin Induced Thrombocytopenia Type II
  Completed · Phase 2 · Interventional · 20 enrolled · Tanabe Pharma Corporation
  NCT00861692updated 2026-01-06
• Study on Safety and Effectiveness of Three Doses of Argatroban as Anticoagulant in Percutaneous Coronary Intervention (PCI)
  Completed · Phase 2 · Interventional · 140 enrolled · Tanabe Pharma Corporation
  NCT00508924updated 2026-01-06
• Safety of Argatroban Infusion in Conduction Disturbances
  Completed · Phase 4 · Interventional · 50 enrolled · Tanabe Pharma GmbH
  NCT05740371updated 2025-12-30
• HEPARINS: INTERFERENCE IN ARGATROBAN MEASUREMENT
  Recruiting · Observational · 70 enrolled · University Hospital, Strasbourg, France
  NCT07302620updated 2025-12-24
• Multi-arm Optimization of Stroke Thrombolysis
  Completed · Phase 3 · Interventional · 514 enrolled · Washington University School of Medicine
  NCT03735979updated 2025-02-07
• Comparing Anticoagulation Strategies Using UFH, Argatroban and LMWH for ECMO Support
  Recruiting · Phase 4 · Interventional · 90 enrolled · Medical University of Vienna
  NCT06442267updated 2024-10-29
• Safety and Feasibility of Argatroban As Anticoagulant in Adults with ECMO
  Completed · Phase 2 · Phase 3 · Interventional · 40 enrolled · Medical University of Vienna
  NCT05226442updated 2024-09-19
• The DESyne BDS Plus RCT: A Randomized Clinical Trial to Assess the Elixir DESyne BDS Plus Drug Eluting Coronary Stent System for the Treatment of de Novo Native Coronary Artery Lesions
  Active not recruiting · Phase 2 · Interventional · 200 enrolled · Elixir Medical Corporation
  NCT05033964updated 2024-08-27
• Safety and Efficacy of Argatroban Applicated in Anticoagulation of V-V ECMO
  Completed · Interventional · 20 enrolled · Beijing Chao Yang Hospital
  NCT04925167updated 2024-03-26

Frequently asked questions

How does Argatroban work?

Argatroban is a direct thrombin inhibitor that reversibly binds to the thrombin active site. Argatroban does not require the co-factor antithrombin III for antithrombotic activity.

What is Argatroban used for?

According to FDA labeling, Argatroban carries indications including: 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).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Argatroban?

Argatroban is classified as Direct thrombin inhibitors, Anti-coagulant, Direct Thrombin Inhibitor, Antithrombins, Thrombin Inhibitors, Decreased Coagulation Factor Activity, Decreased Platelet Aggregation.

What are the contraindications for Argatroban?

Argatroban labeling lists contraindications including: Argatroban is contraindicated in: Patients with major bleeding, [see Warnings and Precautions (5.1) ] Patients with a history of hypersensitivity to argatroban.. Always consult the full prescribing information and a clinician.