Argatroban

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 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
• Argatroban Injection 50 mg/50 mL (1 mg/mL) is ready for intravenous infusion
• Dilution is not required
• Heparin-Induced Thrombocytopenia The dose for heparin-induced thrombocytopenia without hepatic impairment is 2 mcg/kg/min administered as a continuous infusion
• 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
• 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. …

Injection: 250 mg/2.5 mL (100 mg/mL) single-dose vial Injection: 50 mg/50 mL (1 mg/mL) ready for intravenous infusion single-dose vial Injection: 250 mg/2.5 mL (100 mg/mL) single-dose vial. (3) Injection: 50 mg/50 mL (1 mg/mL) ready for intravenous infusion single-dose vial. ( 3 )

• Safety and effectiveness have not been established
• In pediatric patients
• Argatroban was studied among 18 seriously ill
• Pediatric patients who required an alternative to heparin anticoagulation
• Most patients were diagnosed with HIT or suspected HIT
• Age ranges of patients were

Of the total number of subjects (1340) in clinical studies of argatroban, 35% were 65 and over. In the clinical studies of adult patients with HIT (with or without thrombosis), the effectiveness of argatroban was not affected by age. No trends were observed across age groups for both aPTT and the ACT. The safety analysis did suggest that older patients had increased underlying conditions, which may predispose them to adverse reactions. …

• Inform patients of the risks associated with Argatroban Injection as well as the plan for regular monitoring during administration of the drug
• Specifically, inform patients to report: the use of any other products known to affect bleeding. any medical history that may increase the risk for bleeding, including a history of severe hypertension; recent lumbar puncture or 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. any bleeding signs or symptoms. …

• Argatroban is contraindicated in: Patients with major bleeding, [see Warnings and Precautions ] Patients with a history of hypersensitivity to argatroban
• Airway, skin, and generalized hypersensitivity reactions have been reported [see Adverse Reactions ] Major bleeding History of hypersensitivity to this product

Heparin: Allow sufficient time for heparin’s effect on activated partial thromboplastin time (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. …

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 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 . …

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 ) . …

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. …

Take it when you remember, unless it is nearly time for the next dose. Then skip the missed one. Never take two doses at once to make up for it. Check your leaflet, as some medicines are different.