Argatroban - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS Hemorrhage can occur.

Unexplained fall in hematocrit or blood pressure may indicate hemorrhage.

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.

5.1 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 ] has 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 ].

Also, upon cessation of argatroban infusion in the hepatically impaired patient, full reversal of anticoagulant effects may require longer than 4 hours due to decreased clearance and increased elimination half-life of argatroban [ see Dosage and Administration and Clinical Pharmacology ].

Avoid the use of high doses of argatroban in patients undergoing PCI who have clinically significant hepatic disease or AST/ALT levels greater than or equal to 3 times the upper limit of normal.

5.3 Laboratory Tests Anticoagulation effects associated with argatroban infusion at doses up to 40 mcg/kg/min correlate with increases of the aPTT.

Although other global clot-based tests including prothrombin time (PT), the International Normalized Ratio (INR), and thrombin time (TT) are affected by argatroban, the therapeutic ranges for these tests have not been identified for argatroban therapy.

In clinical trials in PCI, the ACT was used for monitoring argatroban anticoagulant activity during the procedure.

The concomitant use of argatroban and warfarin results in prolongation of the PT and INR beyond that produced by warfarin alone [ see Dosage and Administration and Clinical Pharmacology ].