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SELECTED IMPORTANT SAFETY INFORMATION (CONT’D) WARNING: (B) SPINAL/EPIDURAL HEMATOMA (B) Epidural or spinal hematomas may occur in patients treated with ELIQUIS who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. Consider these risks when scheduling patients for spinal procedures. Factors that can increase the risk of developing epidural or spinal hematomas in these patients include: • use of indwelling epidural catheters • concomitant use of other drugs that affect hemostasis, such as nonsteroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants • a history of traumatic or repeated epidural or spinal punctures • a history of spinal deformity or spinal surgery • optimal timing between the administration of ELIQUIS and neuraxial procedures is not known Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated. puncture. If traumatic puncture occurs, delay the administration of ELIQUIS for 48 hours. Monitor patients frequently and if neurological compromise is noted, urgent diagnosis and treatment is necessary. Physicians should consider the potential benefit versus the risk of neuraxial intervention in ELIQUIS patients. • Prosthetic Heart Valves: The safety and efficacy of ELIQUIS have not been studied in patients with prosthetic heart valves and is not recommended in these patients. • Acute PE in Hemodynamically Unstable Patients or Patients who Require Thrombolysis or Pulmonary Embolectomy: Initiation of ELIQUIS is not recommended as an alternative to unfractionated heparin for the initial treatment of patients with PE who present with hemodynamic instability or who may receive thrombolysis or pulmonary embolectomy. ADVERSE REACTIONS • The most common and most serious adverse reactions reported with ELIQUIS were related to bleeding. TEMPORARY INTERRUPTION FOR SURGERY AND OTHER INTERVENTIONS • ELIQUIS should be discontinued at least 48 hours prior to elective surgery or invasive procedures with a moderate or high risk of unacceptable or clinically significant bleeding. ELIQUIS should be discontinued at least 24 hours prior to elective surgery or invasive CONTRAINDICATIONS procedures with a low risk of bleeding or where the bleeding would be noncritical in location and easily controlled. Bridging anticoagulation • Active pathological bleeding during the 24 to 48 hours after stopping ELIQUIS and prior to the • Severe hypersensitivity reaction to ELIQUIS (e.g., anaphylactic reactions) intervention is not generally required. ELIQUIS should be restarted after WARNINGS AND PRECAUTIONS the surgical or other procedures as soon as adequate hemostasis has • Increased Risk of Thrombotic Events After Premature Discontinuation: been established. Premature discontinuation of any oral anticoagulant, including ELIQUIS, DRUG INTERACTIONS in the absence of adequate alternative anticoagulation increases the • Strong Dual Inhibitors of CYP3A4 and P-gp: Inhibitors of cytochrome risk of thrombotic events. An increased rate of stroke was observed P450 3A4 (CYP3A4) and P-glycoprotein (P-gp) increase exposure to apixaban during the transition from ELIQUIS to warfarin in clinical trials in atrial and increase the risk of bleeding. For patients receiving ELIQUIS doses of fibrillation patients. If ELIQUIS is discontinued for a reason other than 5 mg or 10 mg twice daily, reduce the dose of ELIQUIS by 50% when pathological bleeding or completion of a course of therapy, consider ELIQUIS is coadministered with drugs that are strong dual inhibitors of coverage with another anticoagulant. CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, ritonavir, or • Bleeding Risk: ELIQUIS increases the risk of bleeding and can cause clarithromycin). In patients already taking 2.5 mg twice daily, avoid serious, potentially fatal, bleeding. coadministration of ELIQUIS with strong dual inhibitors of CYP3A4 and P-gp. – Concomitant use of drugs affecting hemostasis increases the risk of • Strong Dual Inducers of CYP3A4 and P-gp: Avoid concomitant use of bleeding, including aspirin and other antiplatelet agents, other ELIQUIS with strong dual inducers of CYP3A4 and P-gp (e.g., rifampin, anticoagulants, heparin, thrombolytic agents, SSRIs, SNRIs, and carbamazepine, phenytoin, St. John’s wort) because such drugs will NSAIDs. decrease exposure to apixaban and increase the risk of stroke and other – Advise patients of signs and symptoms of blood loss and to report thromboembolic events. them imme F