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boxed warning
WARNING: (A) PREMATURE DISCONTINUATION OF RIVAROXABAN INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA WARNING: (A) PREMATURE DISCONTINUATION OF RIVAROXABAN INCREASES THE RISK OF THROMBOTIC EVENTS, (B) SPINAL/EPIDURAL HEMATOMA See full prescribing information for complete boxed warning. (A) Premature discontinuation of rivaroxaban increases the risk of thrombotic events Premature discontinuation of any oral anticoagulant, including rivaroxaban, increases the risk of thrombotic events. To reduce this risk, consider coverage with another anticoagulant if rivaroxaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy. ( 2.2 , 2.3 , 5.1 , 14.1 ) (B) Spinal/epidural hematoma Epidural or spinal hematomas have occurred in patients treated with rivaroxaban who are receiving neuraxial anesthesia or undergoing spinal puncture. These hematomas may result in long-term or permanent paralysis. ( 5.2 , 5.3 , 6.2 ) Monitor patients frequently for signs and symptoms of neurological impairment and if observed, treat urgently. Consider the benefits and risks before neuraxial intervention in patients who are or who need to be anticoagulated. ( 5.3 ) A. Premature discontinuation of rivaroxaban increases the risk of thrombotic events Premature discontinuation of any oral anticoagulant, including rivaroxaban, increases the risk of thrombotic events. If anticoagulation with rivaroxaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.3 , 2.4) , Warnings and Precautions (5.1) , and Clinical Studies (14.1) ] . B. Spinal/epidural hematoma Epidural or spinal hematomas have occurred in patients treated with rivaroxaban 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 non-steroidal anti-inflammatory drugs (NSAIDs), platelet inhibitors, other anticoagulants a history of traumatic or repeated epidural or spinal punctures a history of spina...
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warnings and cautions
5 WARNINGS AND PRECAUTIONS Risk of bleeding: Rivaroxaban can cause serious and fatal bleeding. An agent to reverse the activity of rivaroxaban is available. ( 5.2 ) Pregnancy-related hemorrhage: Use rivaroxaban with caution in pregnant women due to the potential for obstetric hemorrhage and/or emergent delivery. ( 5.7 , 8.1 ) Prosthetic heart valves: Rivaroxaban use not recommended. ( 5.8 ) Increased Risk of Thrombosis in Patients with Triple Positive Antiphospholipid Syndrome: Rivaroxaban use not recommended. ( 5.10 ) 5.1 Increased Risk of Thrombotic Events after Premature Discontinuation Premature discontinuation of any oral anticoagulant, including rivaroxaban, in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from rivaroxaban to warfarin in clinical trials in atrial fibrillation patients. If rivaroxaban is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant [see Dosage and Administration (2.3 , 2.4) and Clinical Studies (14.1) ] . 5.2 Risk of Bleeding Rivaroxaban increases the risk of bleeding, including in any organ, and can cause serious or fatal bleeding. In deciding whether to prescribe rivaroxaban tablets to patients at increased risk of bleeding, the risk of thrombotic events should be weighed against the risk of bleeding. Promptly evaluate any signs or symptoms of blood loss and consider the need for blood replacement. Discontinue rivaroxaban tablets in patients with active pathological hemorrhage. The terminal elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to 45 years. Concomitant use of other drugs that impair hemostasis increases the risk of bleeding. These include aspirin, P2Y 12 platelet inhibitors, dual antiplatelet therapy, other antithrombotic agents, fibrinolytic therapy, non-steroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions (7.4) ] , selective serotonin reuptake inhibitors, and serotonin norepinephrine reuptake inhibitors. Concomitant use of drugs that are known combined P-gp and strong CYP3A inhibitors increases rivaroxaban exposure and may increase bleeding risk [see Drug Interactions (7.2) ] . Risk of Hemorrhage in Acutely Ill Medical Patients at High Risk of Bleeding Acutely ill medical...
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adverse reactions
6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed in other sections of the labeling: Increased Risk of Stroke After Discontinuation in Nonvalvular Atrial Fibrillation [see Boxed Warning and Warnings and Precautions (5.1) ] Bleeding Risk [see Warnings and Precautions (5.2 , 5.4 , 5.5 , 5.6 , 5.7) ] Spinal/Epidural Hematoma [see Boxed Warning and Warnings and Precautions (5.3) ] The most common adverse reaction (>5%) in adult patients was bleeding. ( 6.1 ) The most common adverse reactions (>10%) in pediatric patients were bleeding, cough, vomiting, and gastroenteritis. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Changzhou Pharmaceutical Factory at 1-800-947-0391 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. During clinical development for the approved indications, 34,947 adult patients were exposed to rivaroxaban. Hemorrhage The most common adverse reactions with rivaroxaban were bleeding complications [see Warnings and Precautions (5.2) ] . Nonvalvular Atrial Fibrillation In the ROCKET AF trial, the most frequent adverse reactions associated with permanent drug discontinuation were bleeding events, with incidence rates of 4.3% for rivaroxaban vs. 3.1% for warfarin. The incidence of discontinuations for non-bleeding adverse events was similar in both treatment groups. Table 5 shows the number of patients experiencing various types of bleeding events in the ROCKET AF trial. Table 5: Bleeding Events in ROCKET AF Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories. These events occurred during treatment or within 2 days of stopping treatment. - On Treatment Plus 2 Days Parameter Rivaroxaban N=7111 n (%/year) Warfarin N=7125 n (%/year) Rivaroxaban vs. Warfarin HR (95% CI) Abbreviations: HR = Hazard Ratio, CI = Confidence interval, CRNM = Clinically Relevant Non-Major. Major Bleeding Defined as clinically overt bleeding associated with a decrease in hemoglobin of ≥2 g/dL, a transfusion of ≥2 units of packed red bl...
adverse reactions table
Table 5: Bleeding Events in ROCKET AF Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories. These events occurred during treatment or within 2 days of stopping treatment.- On Treatment Plus 2 Days ParameterRivaroxaban N=7111 n (%/year)Warfarin N=7125 n (%/year)Rivaroxaban vs. Warfarin HR (95% CI)Abbreviations: HR = Hazard Ratio, CI = Confidence interval, CRNM = Clinically Relevant Non-Major.Major Bleeding Defined as clinically overt bleeding associated with a decrease in hemoglobin of ≥2 g/dL, a transfusion of ≥2 units of packed red blood cells or whole blood, bleeding at a critical site, or with a fatal outcome.395 (3.6)386 (3.5)1.04 (0.90, 1.20) Intracranial Hemorrhage (ICH) Intracranial bleeding events included intraparenchymal, intraventricular, subdural, subarachnoid and/or epidural hematoma.55 (0.5)84 (0.7)0.67 (0.47, 0.93) Hemorrhagic Stroke Hemorrhagic stroke in this table specifically refers to non-traumatic intraparenchymal and/or intraventricular hematoma in patients on treatment plus 2 days.36 (0.3)58 (0.5)0.63 (0.42, 0.96) Other ICH19 (0.2)26 (0.2)0.74 (0.41, 1.34) Gastrointestinal (GI) Gastrointestinal bleeding events included upper GI, lower GI, and rectal bleeding.221 (2.0)140 (1.2)1.61 (1.30, 1.99) Fatal Bleeding Fatal bleeding is adjudicated death with the primary cause of death from bleeding.27 (0.2)55 (0.5)0.50 (0.31, 0.79) ICH24 (0.2)42 (0.4)0.58 (0.35, 0.96) Non-intracranial3 (0.0)13 (0.1)0.23 (0.07, 0.82)