M-APIXABAN

• Clinically significant active bleeding, including gastrointestinal bleeding. , recent cerebral infarction (ischemic or hemorrhagic), active peptic ulcer disease with recent bleeding, patients with spontaneous or acquired impairment of hemostasis.

, ritonavir (see WARNINGS AND PRECAUTIONS, Drug Interactions, and DRUG INTERACTIONS, Inhibitors of both CYP 3A4 and P-gp) • Concomitant treatment with any other anticoagulant, including o unfractionated heparin (UFH), except at doses used to maintain a patent central venous or arterial catheter, o low molecular weight heparins (LMWH), such as enoxaparin and dalteparin, o heparin derivatives, such as fondaparinux, and o oral anticoagulants, such as warfarin, dabigatran, rivaroxaban, except under circumstances of switching therapy to or from apixaban.

• Hypersensitivity to M-APIXABAN (apixaban) or to any ingredients of the formulation. For a complete listing of ingredients see DOSAGE FORMS, COMPOSITION AND PACKAGING. WARNINGS AND PRECAUTIONS PREMATURE DISCONTINUATION OF ANY ORAL ANTICOAGULANT, INCLUDING M-APIXABAN, INCREASES THE RISK OF THROMBOTIC EVENTS.

To reduce this risk, consider coverage with another anticoagulant if M-APIXABAN is discontinued for a reason other than pathological bleeding or completion of a course of therapy. The following Warnings and Precautions are listed in alphabetical order.

Bleeding The possibility of a hemorrhage should be considered in evaluating the condition of any anticoagulated patient. As with all anticoagulants, M-APIXABAN (apixaban) should be used with caution in circumstances associated with an increased risk of bleeding.

Bleeding can occur at any site during therapy with M-APIXABAN. An unexplained fall in hemoglobin, hematocrit or blood pressure should lead to a search for a bleeding site. Patients should be advised of signs and symptoms of blood loss and to report them immediately or go to an emergency room.

M-APIXABAN (apixaban) Product Monograph Page 5 of 84 Patients at high risk of bleeding should not be prescribed M-APIXABAN (see CONTRAINDICATIONS). Should severe bleeding occur, treatment with M-APIXABAN must be discontinued and the source of bleeding investigated promptly.

, looking for signs of bleeding or anemia) is recommended throughout the treatment period. g. , especially if other factors/conditions that generally increase the risk of hemorrhage are also present. (see Table 1 below). Table 1 – Factors Which Increase Hemorrhagic Risk Factors increasing apixaban plasma levels Severe renal impairment (eCrCl < 30 mL/min) Concomitant systemic treatment with strong inhibitors of both CYP 3A4 and P-gp Pharmacodynamic interactions NSAID Platelet aggregation inhibitors, including ASA, clopidogrel, prasugrel, ticagrelor Selective serotonin reuptake inhibitors (SSRI), and serotonin norepinephrine reuptake inhibitors (SNRIs) Diseases / procedures with special hemorrhagic risks Congenital or acquired coagulation disorders Thrombocytopenia or functional platelet defects Uncontrolled severe arterial hypertension Active ulcerative gastrointestinal disease Recent gastrointestinal bleeding Recent intracranial hemorrhage Intraspinal or intracerebral vascular abnormalities Recent brain, spinal or ophthalmological surgery Bronchiectasis or history of pulmonary bleeding Others Age > 75 years Concomitant use of M-APIXABAN with drugs affecting hemostasis increases the risk of bleeding.