SANDOZ APIXABAN

, Hepatic Impairment, and ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics). Sandoz Apixaban Tablet should be used with caution in patients with mild or moderate hepatic impairment (Child Pugh A or B). No dose adjustment is required in patients with mild or moderate hepatic impairment (see WARNINGS AND PRECAUTIONS, Hepatic Impairment, and ACTION AND CLINICAL PHARMACOLOGY, Hepatic Impairment).

5 x ULN) were excluded in clinical trials. Therefore, Sandoz Apixaban Tablet should be used with caution in these patients. Concomitant Use of Antiplatelet Agents The concomitant use of Sandoz Apixaban Tablet with antiplatelet agents increases the risk of bleeding (see WARNINGS AND PRECAUTIONS, Bleeding).

If concomitant antiplatelet therapy is contemplated for indications related to coronary artery disease, a careful assessment of the potential risks should be made against potential benefits, weighing risk of increased bleeding against expected benefit (see ADVERSE REACTIONS, Bleeding, Stroke Prevention in Patients with Atrial Fibrillation, and DRUG INTERACTIONS, Drug Products Affecting Hemostasis).

, ritonavir) (see CONTRAINDICATIONS, and WARNINGS AND PRECAUTIONS, Inhibitors of Both CYP 3A4 and P-gp). Drugs moderately inhibiting the apixaban elimination pathways, CYP 3A4 and/or P-gp, would be expected to increase apixaban plasma concentrations to a lesser extent.

For example, concomitant administration of diltiazem led to a 40% increase in apixaban AUC, while naproxen, an inhibitor of P-gp, led to a 50% increase in apixaban AUC and clarithromycin, an inhibitor of P-gp, led to a 60% increase in apixaban AUC.

No dose adjustment for apixaban is required when co-administered with less potent inhibitors of CYP 3A4 and/or P-gp (see WARNINGS AND PRECAUTIONS, Bleeding and DRUG INTERACTIONS, Table 10). Inducers of Both CYP 3A4 and P-gp Co-administration of apixaban with rifampicin, a strong inducer of both CYP 3A4 and P-gp, led to an approximate 54% decrease in apixaban AUC.

, phenytoin, carbamazepine, phenobarbital or St. John’s Wort) may also lead to reduced apixaban plasma concentrations. Combined use of Sandoz Apixaban Tablet with strong inducers of both CYP 3A4 and P-gp should generally be avoided since efficacy of Sandoz Apixaban Tablet may be compromised.

(see WARNINGS AND PRECAUTIONS, Inducers of Both CYP 3A4 and P-gp). Body Weight Sandoz Apixaban Tablet (apixaban tablets) Page 27 of 75 Prevention of VTE following Elective Hip or Knee Replacement Surgery No dose adjustment required.