rivaroxaban
Tablet, Film Coated · Oral
Uses
Rivaroxaban tablets are a factor Xa inhibitor indicated: to reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD) ( 1.7 ) to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including patients after recent lower extremity revascularization due to symptomatic PAD ( 1.8 ) 1.7 Reduction of Risk of Major Cardiovascular Events in Patients with Coronary Artery Disease (CAD) Rivaroxaban tablets, in combination with aspirin, is indicated to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in adult patients with coronary artery disease. 1.8 Reduction of Risk of Major Thrombotic Vascular Events in Patients with Peripheral Artery Disease (PAD), Including Patients after Lower Extremity Revascularization due to Symptomatic PAD Rivaroxaban tablets, in combination with aspirin, is indicated to reduce the risk of major thrombotic vascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology) in adult patients with PAD, including patients who have recently undergone a lower extremity revascularization procedure due to symptomatic PAD.
Dosage and administration
2 DOSAGE AND ADMINISTRATION CAD or PAD: 2.5 mg orally twice daily with or without food, in combination with aspirin (75 to 100 mg) once daily ( 2.1 ) 2.1 Recommended Dosage in Adults Table 1: Recommended Dosage in Adults Indication Renal Considerations * Dosage Food/Timing † Reduction of Risk of Major Cardiovascular Events (CV Death, MI, and Stroke) in CAD No dose adjustment needed based on CrCl 2.5 mg twice daily , plus aspirin (75 to 100 mg) once daily Take with or without food Reduction of Risk of Major Thrombotic Vascular Events in PAD, Including Patients after Lower Extremity Revascularization due to Symptomatic PAD No dose adjustment needed based on CrCl 2.5 mg twice daily , plus aspirin (75 to 100 mg) once daily. When starting therapy after a successful lower extremity revascularization procedure, initiate once hemostasis has been established. Take with or without food * Calculate CrCl based on actual weight. [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.6 )] † [See Clinical Pharmacology ( 12.3 )] 2.2 Recommended Dosage in Pediatric Patients Rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients [see Use in Specific Populations (8.4)] . 2.3 Switching to and from Rivaroxaban Switching from Warfarin to R ivaroxaban - When switching patients from warfarin to rivaroxaban, discontinue warfarin and start rivaroxaban as soon as the International Normalized Ratio (INR) is below 3.0 in adults patients to avoid periods of inadequate anticoagulation. Switching from Rivaroxaban to Warfarin – Adults: No clinical trial data are available to guide converting patients from rivaroxaban to warfarin. Rivaroxaban affects INR, so INR measurements made during co-administration with warfarin may not be useful for determining the appropriate dose of warfarin. One approach is to discontinue rivaroxaban and begin both a parenteral anticoagulant and warfarin at the time the next dose of rivaroxaban would have been taken. Once rivaroxaban is discontinued, INR testing may be done reliably 24 hours after the last dose. Switching from Rivaroxaban to Anticoagulants other than Warfarin - For adult and pediatric patients currently taking rivaroxaban and transitioning to an anticoagulant with rapid onset, discontinue rivaroxaban and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next rivaroxaban dose would have been taken [see Drug Interactions ( 7.4 )] . Switching from Anticoagulants other than Warfarin to Rivaroxaban - For adult patients currently receiving an anticoagulant other than warfarin, start rivaroxaban 0 to 2 hours prior to the next scheduled administration of the drug (e.g., low molecular weight heparin or non-warfarin oral anticoagulant) and omit administration of the other anticoagulant. For unfractionated heparin being administered by continuous infusion, stop the infusion and start rivaroxaban at the same time. 2.4 Discontinuation for Surgery and other Interventions If anticoagulation must be discontinued to reduce the risk of bleeding with surgical or other procedures, rivaroxaban should be stopped at least 24 hours before the procedure to reduce the risk of bleeding [see Warnings and Precautions ( 5.2 )] . In deciding whether a procedure should be delayed until 24 hours after the last dose of rivaroxaban, the increased risk of bleeding should be weighed against the urgency of intervention. Rivaroxaban should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established, noting that the time to onset of therapeutic effect is short [see Warnings and Precautions ( 5.1 )] . If oral medication cannot be taken during or after surgical intervention, consider administering a parenteral anticoagulant. 2.5 Missed Dose Adults For patients receiving 2.5 mg twice daily: if a dose is missed, the patient should take a single 2.5 mg rivaroxaban dose as recommended at the next scheduled time. On the following day, the patient should continue with their regular regimen. 2.6 Administration Options For adult patients who are unable to swallow whole tablets, rivaroxaban tablets may be crushed and mixed with applesauce immediately prior to use and administered orally. Administration with food is not required for the 2.5 mg tablets [see Clinical Pharmacology ( 12.3 )] . Administration of rivaroxaban tablets via nasogastric (NG) tube or gastric feeding tube: After confirming gastric placement of the tube, rivaroxaban tablets (all strengths) may be crushed and suspended in 50 mL of water and administered via an NG tube or gastric feeding tube. Since rivaroxaban absorption is dependent on the site of drug release, avoid administration of rivaroxaban tablets distal to the stomach which can result in reduced absorption and thereby, reduced drug exposure. After the administration of a crushed rivaroxaban 15 mg or 20 mg tablet, the dose should then be immediately followed by enteral feeding. Enteral feeding is not required following administration of the 2.5 mg or 10 mg tablets [see Clinical Pharmacology ( 12.3 )]. Crushed rivaroxaban tablets are stable in water and in applesauce for up to 4 hours. An in vitro compatibility study indicated that there is no adsorption of rivaroxaban from a water suspension of a crushed rivaroxaban tablet to PVC or silicone nasogastric (NG) tubing.
Dosage forms and strengths
2.5 mg tablets: Round, light yellow, biconvex, film-coated tablets with engraving 2.5 on one side and plain other side. Tablets: 2.5 mg ( 3 )
Contraindications
Rivaroxaban is contraindicated in patients with: active pathological bleeding [see Warnings and Precautions ( 5.2 )] severe hypersensitivity reaction to rivaroxaban (e.g., anaphylactic reactions) [see Adverse Reactions ( 6.2 )] Active pathological bleeding ( 4 ) Severe hypersensitivity reaction to rivaroxaban ( 4 )
Warnings and precautions
Risk of bleeding: Rivaroxaban can cause serious and fatal bleeding. ( 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 )] . 5.2 Risk of Bleeding Rivaroxabanincreases the risk of bleeding, including in any organ, and can cause serious or fatal bleeding. In deciding whether to prescribe rivaroxabanto 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 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 )]. Reversal of Anticoagulant Effect A specific agent to reverse the anti-factor Xa activity of rivaroxaban is not available. Because of high plasma protein binding, rivaroxaban is not dialyzable [see Clinical Pharmacology ( 12.3 )]. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. Use of procoagulant reversal agents, such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate or recombinant factor VIIa, may be considered but has not been evaluated in clinical efficacy and safety studies. Monitoring for the anticoagulation effect of rivaroxaban using a clotting test (PT, INR or aPTT) or anti-factor Xa (FXa) activity is not recommended. 5.3 Spinal/Epidural Anesthesia or Puncture When neuraxial anesthesia (spinal/epidural anesthesia) or spinal puncture is employed, patients treated with anticoagulant agents for prevention of thromboembolic complications are at risk of developing an epidural or spinal hematoma which can result in long-term or permanent paralysis [see Boxed Warning]. To reduce the potential risk of bleeding associated with the concurrent use of rivaroxaban and epidural or spinal anesthesia/analgesia or spinal puncture, consider the pharmacokinetic profile of rivaroxaban [see Clinical Pharmacology ( 12.3 )]. Placement or removal of an epidural catheter or lumbar puncture is best performed when the anticoagulant effect of rivaroxaban is low; however, the exact timing to reach a sufficiently low anticoagulant effect in each patient is not known. An indwelling epidural or intrathecal catheter should not be removed before at least 2 half-lives have elapsed (i.e., 18 hours in young patients aged 20 to 45 years and 26 hours in elderly patients aged 60 to 76 years), after the last administration of rivaroxaban [see Clinical Pharmacology ( 12.3 )]. The next rivaroxaban dose should not be administered earlier than 6 hours after the removal of the catheter. If traumatic puncture occurs, delay the administration of rivaroxaban for 24 hours. Should the physician decide to administer anticoagulation in the context of epidural or spinal anesthesia/analgesia or lumbar puncture, monitor frequently to detect any signs or symptoms of neurological impairment, such as midline back pain, sensory and motor deficits (numbness, tingling, or weakness in lower limbs), bowel and/or bladder dysfunction. Instruct patients to immediately report if they experience any of the above signs or symptoms. If signs or symptoms of spinal hematoma are suspected, initiate urgent diagnosis and treatment including consideration for spinal cord decompression even though such treatment may not prevent or reverse neurological sequelae. 5.4 Use in Patients with Renal Impairment Discontinue rivaroxaban in patients who develop acute renal failure while on treatment [see Use in Specific Populations ( 8.6 )]. 5.5 Use in Patients with Hepatic Impairment No clinical data are available for adult patients with severe hepatic impairment. Avoid use of rivaroxaban in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy since drug exposure and bleeding risk may be increased [see Use in Specific Populations ( 8.7 )]. 5.6 Use with P-gp and Strong CYP3A Inhibitors or Inducers Avoid concomitant use of rivaroxaban with known combined P-gp and strong CYP3A inhibitors [see Drug Interactions ( 7.2 )]. Avoid concomitant use of rivaroxaban with drugs that are known combined P-gp and strong CYP3A inducers [see Drug Interactions ( 7.3 )]. 5.7 Risk of Pregnancy-Related Hemorrhage In pregnant women, rivaroxaban should be used only if the potential benefit justifies the potential risk to the mother and fetus.
Side effects
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 ) To report SUSPECTED ADVERSE REACTIONS, contact Micro Labs USA Inc. at 1-855-839-8195 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. Hemorrhage The most common adverse reactions with rivaroxaban were bleeding complications [see Warnings and Precautions ( 5.2 )] . Reduction of Risk of Major Cardiovascular Events in Patients with CAD In the COMPASS trial overall, the most frequent adverse reactions associated with permanent drug discontinuation were bleeding events, with incidence rates of 2.7% for rivaroxaban 2.5 mg twice daily vs. 1.2% for placebo on background therapy for all patients with aspirin 100 mg once daily. The incidences of important bleeding events in the CAD and PAD populations in COMPASS were similar. Table 10 shows the number of patients experiencing various types of major bleeding events in the COMPASS trial. Table 10: Major Bleeding Events in COMPASS - On Treatment Plus 2 Days* Parameter Rivaroxaban † N=9134 n (%/year) Placebo † N=9107 n (%/year) Rivaroxaban vs. Placebo HR (95 % CI) Modified ISTH Major Bleeding ‡ 263 (1.6) 144 (0.9) 1.8 (1.5, 2.3) - Fatal bleeding event Intracranial hemorrhage (ICH) Non-intracranial 12 (<0.1) 6 (<0.1) 6 (<0.1) 8 (<0.1) 3 (<0.1) 5 (<0.1) 1.5 (0.6, 3.7) 2.0 (0.5, 8.0) 1.2 (0.4, 4.0) - Symptomatic bleeding in critical organ (non-fatal) - ICH (fatal and non-fatal) Hemorrhagic Stroke Other ICH 58 (0.3) 23 (0.1) 18 (0.1) 6 (<0.1) 43 (0.3) 21 (0.1) 13 (<0.1) 9 (<0.1) 1.4 (0.9, 2.0) 1.1 (0.6, 2.0) 1.4 (0.7, 2.8) 0.7 (0.2, 1.9) - Bleeding into the surgical site requiring reoperation (non-fatal, not in critical organ) 7 (<0.1) 6 (<0.1) 1.2 (0.4, 3.5) - Bleeding leading to hospitalization (non-fatal, not in critical organ, not requiring reoperation) 188 (1.1) 91 (0.5) 2.1 (1.6, 2.7) Major GI bleeding 117 (0.7) 49 (0.3) 2.4 (1.7, 3.4) * 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 in the safety analysis set in COMPASS patients. † Treatment schedule: Rivaroxaban 2.5 mg twice daily or placebo. All patients received background therapy with aspirin 100 mg once daily. ‡ Defined as i) fatal bleeding, or ii) symptomatic bleeding in a critical area or organ, such as intraarticular, intramuscular with compartment syndrome, intraspinal, intracranial, intraocular, respiratory, pericardial, liver, pancreas, retroperitoneal, adrenal gland or kidney; or iii) bleeding into the surgical site requiring reoperation, or iv) bleeding leading to hospitalization. CI: confidence interval; HR: hazard ratio; ISTH: International Society on Thrombosis and Hemostasis Reduction of Risk of Major Thrombotic Vascular Events in Patients with Peripheral Artery Disease (PAD), Including Patients after Lower Extremity Revascularization due to Symptomatic PAD The incidence of premature permanent discontinuation due to bleeding events for rivaroxaban 2.5 mg twice daily vs. placebo on background therapy with aspirin 100 mg once daily in VOYAGER was 4.1% vs. 1.6% and in COMPASS PAD was 2.7% vs. 1.3%, respectively. Table 11 shows the number of patients experiencing various types of TIMI (Thrombolysis in Myocardial Infarction) major bleeding events in the VOYAGER trial. The most common site of bleeding was gastrointestinal. Table 11: Major Bleeding Events * in VOYAGER- On Treatment Plus 2 Days Rivaroxaban † N=3256 Placebo † N=3248 Rivaroxaban vs. Placebo HR (95% CI) Parameter n (%) Event rate %/year n (%) Event rate %/year TIMI Major Bleeding (CABG/non-CABG) 62 (1.9) 0.96 44 (1.4) 0.67 1.4 (1.0, 2.1) Fatal bleeding 6 (0.2) 0.09 6 (0.2) 0.09 1.0 (0.3, 3.2) Intracranial bleeding 13 (0.4) 0.20 17 (0.5) 0.26 0.8 (0.4, 1.6) Clinically overt signs of hemorrhage associated with a drop in hemoglobin of > 5g/dL or drop in hematocrit of > 15% 46 (1.4) 0.71 24 (0.7) 0.36 1.9 (1.2, 3.2) * Major bleeding events within each subcategory were counted once per patient, but patients may have contributed events to multiple subcategories. † Treatments schedule: Rivaroxaban 2.5 mg twice daily or placebo. All patients received background therapy with aspirin 100 mg once daily. CABG: Coronary artery bypass graft; CI: confidence interval; HR: hazard ratio; TIMI: Thrombolysis in Myocardial Infarction Bleeding Criteria Non-bleeding adverse reactions reported in ≥5% of rivaroxaban-treated patients are shown in Table 17. Table 17: Other Adverse Reactions * Reported by ≥5% of Rivaroxaban-Treated Patients in UNIVERSE Study (Part B) Adverse Reaction Rivaroxaban N=64 n (%) Aspirin N=34 n (%) Cough 10 (15.6) 3 (8.8) Vomiting 9 (14.1) 3 (8.8) Gastroenteritis † 8 (12.5) 1 (2.9) Rash † 6 (9.4) 2 (5.9) * Adverse reaction with Relative Risk >1.5 for rivaroxaban versus aspirin. † The following terms were combined: Gastroenteritis: gastroenteritis, gastroenteritis viral Rash: rash, rash maculo-papular, viral rash 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of rivaroxaban.
Drug interactions
Avoid combined P-gp and strong CYP3A inhibitors and inducers ( 7.2 , 7.3 ) Anticoagulants: Avoid concomitant use ( 7.4 ) 7.1 General Inhibition and Induction Properties Rivaroxaban is a substrate of CYP3A4/5, CYP2J2, and the P-gp and ATP-binding cassette G2 (ABCG2) transporters, the latter also known as breast cancer resistance protein (BCRP). Combined P-gp and strong CYP3A inhibitors increase exposure to rivaroxaban and may increase the risk of bleeding. Combined P-gp and strong CYP3A inducers decrease exposure to rivaroxaban and may increase the risk of thromboembolic events. 7.2 Drugs that Inhibit Cytochrome P450 3A Enzymes and Drug Transport Systems Interaction with Combined P-gp and Strong CYP3A Inhibitors Avoid concomitant administration of rivaroxaban with known combined P-gp and strong CYP3A inhibitors (e.g., ketoconazole and ritonavir) [see Warnings and Precautions ( 5.6 ) and Clinical Pharmacology ( 12.3 )] . Although clarithromycin is a combined P-gp and strong CYP3A inhibitor, pharmacokinetic data suggests that no precautions are necessary with concomitant administration with rivaroxaban as the change in exposure is unlikely to affect the bleeding risk [see Clinical Pharmacology ( 12.3 )] . Interaction with Combined P-gp and Moderate CYP3A Inhibitors in Patients with Renal Impairment Rivaroxaban should not be used in patients with CrCl 15 to <80 mL/min who are receiving concomitant combined P-gp and moderate CYP3A inhibitors (e.g., erythromycin) unless the potential benefit justifies the potential risk [see Warnings and Precautions ( 5.4 ) and Clinical Pharmacology ( 12.3 )] . 7.3 Drugs that Induce Cytochrome P450 3A Enzymes and Drug Transport Systems Avoid concomitant use of rivaroxaban with drugs that are combined P-gp and strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s wort) [see Warnings and Precautions ( 5.6 ) and Clinical Pharmacology ( 12.3 )] . 7.4 Anticoagulants and NSAIDs/Aspirin Co-administration of enoxaparin, warfarin, aspirin, clopidogrel and chronic NSAID use may increase the risk of bleeding [see Clinical Pharmacology ( 12.3 )]. Avoid concurrent use of rivaroxaban with other anticoagulants due to increased bleeding risk unless benefit outweighs risk. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with aspirin, other platelet aggregation inhibitors, or NSAIDs [see Warnings and Precautions ( 5.2 )].
Use in specific populations
Renal impairment: Avoid or adjust dose ( 8.6 ) Hepatic impairment: Avoid use in Child-Pugh B and C hepatic impairment or hepatic disease associated with coagulopathy ( 8.7 ) 8.1 Pregnancy Risk Summary The limited available data on rivaroxaban in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Use rivaroxaban with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. The anticoagulant effect of rivaroxaban cannot be reliably monitored with standard laboratory testing. Consider the benefits and risks of rivaroxaban for the mother and possible risks to the fetus when prescribing rivaroxaban to a pregnant woman [see Warnings and Precautions ( 5.2 , 5.7 )] . Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnancy is a risk factor for venous thromboembolism and that risk is increased in women with inherited or acquired thrombophilias. Pregnant women with thromboembolic disease have an increased risk of maternal complications including pre-eclampsia. Maternal thromboembolic disease increases the risk for intrauterine growth restriction, placental abruption and early and late pregnancy loss. Fetal/Neonatal Adverse Reactions Based on the pharmacologic activity of Factor Xa inhibitors and the potential to cross the placenta, bleeding may occur at any site in the fetus and/or neonate. Labor or Delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding and this risk may be increased during labor or delivery [see Warnings and Precautions ( 5.7 )]. The risk of bleeding should be balanced with the risk of thrombotic events when considering the use of rivaroxaban in this setting. Data Human Data There are no adequate or well-controlled studies of rivaroxaban in pregnant women, and dosing for pregnant women has not been established. Post-marketing experience is currently insufficient to determine a rivaroxaban-associated risk for major birth defects or miscarriage. In an in vitro placenta perfusion model, unbound rivaroxaban was rapidly transferred across the human placenta. Animal Data Rivaroxaban crosses the placenta in animals. Rivaroxaban increased fetal toxicity (increased resorptions, decreased number of live fetuses, and decreased fetal body weight) when pregnant rabbits were given oral doses of ≥10 mg/kg rivaroxaban during the period of organogenesis. This dose corresponds to about 4 times the human exposure of unbound drug, based on AUC comparisons at the highest recommended human dose of 20 mg/day. Fetal body weights decreased when pregnant rats were given oral doses of 120 mg/kg during the period of organogenesis. This dose corresponds to about 14 times the human exposure of unbound drug. In rats, peripartal maternal bleeding and maternal and fetal death occurred at the rivaroxaban dose of 40 mg/kg (about 6 times maximum human exposure of the unbound drug at the human dose of 20 mg/day). 8.2 Lactation Risk Summary Rivaroxaban has been detected in human milk. There are insufficient data to determine the effects of rivaroxaban on the breastfed child or on milk production. Rivaroxaban and/or its metabolites were present in the milk of rats. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for rivaroxaban and any potential adverse effects on the breastfed infant from rivaroxaban or from the underlying maternal condition (see Data) . Data Animal Data Following a single oral administration of 3 mg/kg of radioactive [ 14 C]-rivaroxaban to lactating rats between Day 8 to 10 postpartum, the concentration of total radioactivity was determined in milk samples collected up to 32 hours post-dose. The estimated amount of radioactivity excreted with milk within 32 hours after administration was 2.1% of the maternal dose. 8.3 Females and Males of Reproductive Potential Females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. The risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including rivaroxaban should be assessed in females of reproductive potential and those with abnormal uterine bleeding. 8.4 Pediatric Use For the rivaroxaban 2.5 mg tablets, there are no safety, efficacy, pharmacokinetic and pharmacodynamic data to support the use in pediatric patients. Therefore, rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients. 8.5 Geriatric Use Of the total number of adult patients in clinical trials for the approved indications of rivaroxaban (N=64,943 patients), 64 percent were 65 years and over, with 27 percent 75 years and over. In clinical trials the efficacy of rivaroxaban in the elderly (65 years or older) was similar to that seen in patients younger than 65 years. Both thrombotic and bleeding event rates were higher in these older patients [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )]. 8.6 Renal Impairment In pharmacokinetic studies, compared to healthy adult subjects with normal creatinine clearance, rivaroxaban exposure increased by approximately 44 to 64% in adult subjects with renal impairment. Increases in pharmacodynamic effects were also observed [see Clinical Pharmacology ( 12.3 )] .
Pregnancy
8.1 Pregnancy Risk Summary The limited available data on rivaroxaban in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. Use rivaroxaban with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. The anticoagulant effect of rivaroxaban cannot be reliably monitored with standard laboratory testing. Consider the benefits and risks of rivaroxaban for the mother and possible risks to the fetus when prescribing rivaroxaban to a pregnant woman [see Warnings and Precautions ( 5.2 , 5.7 )] . Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Pregnancy is a risk factor for venous thromboembolism and that risk is increased in women with inherited or acquired thrombophilias. Pregnant women with thromboembolic disease have an increased risk of maternal complications including pre-eclampsia. Maternal thromboembolic disease increases the risk for intrauterine growth restriction, placental abruption and early and late pregnancy loss. Fetal/Neonatal Adverse Reactions Based on the pharmacologic activity of Factor Xa inhibitors and the potential to cross the placenta, bleeding may occur at any site in the fetus and/or neonate. Labor or Delivery All patients receiving anticoagulants, including pregnant women, are at risk for bleeding and this risk may be increased during labor or delivery [see Warnings and Precautions ( 5.7 )]. The risk of bleeding should be balanced with the risk of thrombotic events when considering the use of rivaroxaban in this setting. Data Human Data There are no adequate or well-controlled studies of rivaroxaban in pregnant women, and dosing for pregnant women has not been established. Post-marketing experience is currently insufficient to determine a rivaroxaban-associated risk for major birth defects or miscarriage. In an in vitro placenta perfusion model, unbound rivaroxaban was rapidly transferred across the human placenta. Animal Data Rivaroxaban crosses the placenta in animals. Rivaroxaban increased fetal toxicity (increased resorptions, decreased number of live fetuses, and decreased fetal body weight) when pregnant rabbits were given oral doses of ≥10 mg/kg rivaroxaban during the period of organogenesis. This dose corresponds to about 4 times the human exposure of unbound drug, based on AUC comparisons at the highest recommended human dose of 20 mg/day. Fetal body weights decreased when pregnant rats were given oral doses of 120 mg/kg during the period of organogenesis. This dose corresponds to about 14 times the human exposure of unbound drug. In rats, peripartal maternal bleeding and maternal and fetal death occurred at the rivaroxaban dose of 40 mg/kg (about 6 times maximum human exposure of the unbound drug at the human dose of 20 mg/day).
Pediatric use
8.4 Pediatric Use For the rivaroxaban 2.5 mg tablets, there are no safety, efficacy, pharmacokinetic and pharmacodynamic data to support the use in pediatric patients. Therefore, rivaroxaban 2.5 mg tablets are not recommended for use in pediatric patients.
Geriatric use
8.5 Geriatric Use Of the total number of adult patients in clinical trials for the approved indications of rivaroxaban (N=64,943 patients), 64 percent were 65 years and over, with 27 percent 75 years and over. In clinical trials the efficacy of rivaroxaban in the elderly (65 years or older) was similar to that seen in patients younger than 65 years. Both thrombotic and bleeding event rates were higher in these older patients [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )].
Overdosage
Overdose of rivaroxaban may lead to hemorrhage. Discontinue rivaroxaban and initiate appropriate therapy if bleeding complications associated with overdosage occur. Rivaroxaban systemic exposure is not further increased at single doses >50 mg due to limited absorption. The use of activated charcoal to reduce absorption in case of rivaroxaban overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not dialyzable [see Warnings and Precautions ( 5.2 ) and Clinical Pharmacology ( 12.3 )] . Partial reversal of laboratory anticoagulation parameters may be achieved with use of plasma products. A specific agent to reverse the anti-factor Xa activity of rivaroxaban is not available.
Description
Rivaroxaban, a factor Xa (FXa) inhibitor, is the active ingredient in rivaroxaban tablets, USP with the chemical name 5-Chloro-N-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide. The molecular formula of rivaroxaban, USP is C 19 H 18 ClN 3 O 5 S and the molecular weight is 435.89. The structural formula is: Rivaroxaban,USP is a pure ( S )-enantiomer. It is an odorless, non-hygroscopic, white to yellowish crystalline powder. Rivaroxaban, USP is only slightly soluble in organic solvents (e.g., acetone, polyethylene glycol 400) and is practically insoluble in water and aqueous media. Each rivaroxaban tablet, USP contains 2.5 mg rivaroxaban. The inactive ingredients of rivaroxaban tablet, USP are: croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. Additionally, the film coating mixture for rivaroxaban tablets USP, 2.5 mg is Opadry ® Yellow and contains: ferric oxide yellow, hypromellose, polyethylene glycol 3350, and titanium dioxide. FDA approved dissolution test specifications differ from USP rivaroxaban-str-1.jpg
Mechanism of action
12.1 Mechanism of Action Rivaroxaban is a selective inhibitor of FXa. It does not require a cofactor (such as Anti-thrombin III) for activity. Rivaroxaban inhibits free FXa and prothrombinase activity. Rivaroxaban has no direct effect on platelet aggregation, but indirectly inhibits platelet aggregation induced by thrombin. By inhibiting FXa, rivaroxaban decreases thrombin generation.
How supplied
Rivaroxaban Tablets, USP are available in the strength and packages listed below:
• 2.5 mg tablets are round, light yellow, biconvex, film-coated tablets with engraving 2.5 on one face and plain on other face. The tablets are supplied in the packages listed: Bottles of 30: NDC 42571-345-30 Bottles of 60: NDC 42571-345-60 Bottles of 500: NDC 42571-345-05 Store at room temperature between 20 o to 25 o C (68 o to 77 o F); excursions permitted between 15 o to 30 o C (59 o to 86 o F) [see USP Controlled Room Temperature]. Keep out of the reach of children.
Patient information
For the tablets, advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide). Instructions for Patient Use
• Advise patients to take rivaroxaban tablets only as directed.
• Remind patients to not discontinue rivaroxaban tablets without first talking to their healthcare professional. Adults
• Advise patients who cannot swallow the tablet whole to crush rivaroxaban tablets and combine with a small amount of applesauce followed by food [see Dosage and Administration ( 2.6 )] .
• For patients requiring an NG tube or gastric feeding tube, instruct the patient or caregiver to crush the rivaroxaban tablet and mix it with a small amount of water before administering via the tube [see Dosage and Administration ( 2.6 )] .
• If a dose is missed, advise the patient according to the instructions in the Full Prescribing Information based on their dosing schedule [see Dosage and Administration ( 2.5 )] . Bleeding Risks
• Advise patients to report any unusual bleeding or bruising to their physician. Inform patients that it might take them longer than usual to stop bleeding, and that they may bruise and/or bleed more easily when they are treated with rivaroxaban [see Warnings and Precautions ( 5.2 )] .
• If patients have had neuraxial anesthesia or spinal puncture, and particularly, if they are taking concomitant NSAIDs or platelet inhibitors, advise patients to watch for signs and symptoms of spinal or epidural hematoma, such as back pain, tingling, numbness (especially in the lower limbs), muscle weakness, and stool or urine incontinence. If any of these symptoms occur, advise the patient to contact his or her physician immediately [see Boxed Warning ] . Invasive or Surgical Procedures Instruct patients to inform their healthcare professional that they are taking rivaroxaban before any invasive procedure (including dental procedures) is scheduled. Concomitant Medication and Herbals Advise patients to inform their physicians and dentists if they are taking, or plan to take, any prescription or over-the-counter drugs or herbals, so their healthcare professionals can evaluate potential interactions [see Drug Interactions ( 7 )] . Pregnancy and Pregnancy-Related Hemorrhage
• Advise patients to inform their physician immediately if they become pregnant or intend to become pregnant during treatment with rivaroxaban [see Use in Specific Populations ( 8.1 )] .
• Advise pregnant women receiving rivaroxaban to immediately report to their physician any bleeding or symptoms of blood loss [see Warnings and Precautions ( 5.7 )] . Lactation Advise patients to discuss with their physician the benefits and risks of rivaroxaban for the mother and for the child if they are nursing or intend to nurse during anticoagulant treatment [see Use in Specific Populations ( 8.2 )] . Females and Males of Reproductive Potential Advise patients who can become pregnant to discuss pregnancy planning with their physician [see Use in Specific Populations ( 8.3 )] . Trademarks listed are property of their respective owners. Manufactured by: Micro Labs Limited Goa-403 722, INDIA. Manufactured for: Micro Labs USA, Inc. Somerset, NJ 08873 Revised: 07/2026
Label text from the FDA structured product label by Micro Labs Limited (revised Sep 4, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Rivaroxaban in 30 products
rivaroxaban NDC products (32)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 62332-683 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-348 | Rivaroxaban 20 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-240 | Kit | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-347 | Rivaroxaban 15 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 62332-346 | Rivaroxaban 10 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Inc. | ANDA |
| 46708-683 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Limited | ANDA |
| 46708-240 | Kit | Alembic Pharmaceuticals Limited | ANDA |
| 46708-346 | Rivaroxaban 10 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Limited | ANDA |
| 46708-347 | Rivaroxaban 15 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Limited | ANDA |
| 46708-348 | Rivaroxaban 20 mg/1 Tablet, Film Coated | Alembic Pharmaceuticals Limited | ANDA |
| 60505-6256 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Apotex Corp. | ANDA |
| 67877-882 | Rivaroxaban 155 mg/1 Granule, For Suspension | Ascend Laboratories, LLC | ANDA |
| 59651-849 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 31722-496 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Camber Pharmaceuticals, Inc. | ANDA |
| 55488-0540 | Rivaroxaban 10 mg/1 Tablet, Film Coated | Changzhou Pharmaceutical Factory | ANDA |
| 55488-0541 | Rivaroxaban 15 mg/1 Tablet, Film Coated | Changzhou Pharmaceutical Factory | ANDA |
| 55488-0542 | Rivaroxaban 20 mg/1 Tablet, Film Coated | Changzhou Pharmaceutical Factory | ANDA |
| 43598-981 | Rivaroxaban 2.5 mg/1 Tablet | Dr.Reddy's Laboratories, Inc. | ANDA |
| 76282-774 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Exelan pharmaceuticals,Inc | ANDA |
| 71921-405 | Rivaroxaban 2.5 mg/1 Tablet | Florida Pharmaceutical Products, LLC | ANDA |
| 14445-184 | Rivaroxaban 20 mg/1 Tablet, Film Coated | Indoco Remedies Limited | ANDA |
| 14445-183 | Rivaroxaban 15 mg/1 Tablet, Film Coated | Indoco Remedies Limited | ANDA |
| 14445-148 | Rivaroxaban 10 mg/1 Tablet, Film Coated | Indoco Remedies Limited | ANDA |
| 14445-147 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Indoco Remedies Limited | ANDA |
| 68180-709 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Lupin Pharmaceuticals, Inc. | ANDA |
| 33342-488 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Macleods Pharmaceuticals Limited | ANDA |
| 42571-345 | Rivaroxaban 2.5 mg/1 Tablet | Micro Labs Limited | ANDA |
| 72603-890 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | NorthStar RxLLC | ANDA |
| 72205-416 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | Novadoz Pharmaceuticals LLC | ANDA |
| 50228-513 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | ScieGen pharmaceuticals,Inc | ANDA |
| 51672-4228 | Rivaroxaban 2.5 mg/1 Tablet, Coated | Sun Pharmaceutical Industries, Inc. | ANDA |
| 72865-321 | Rivaroxaban 2.5 mg/1 Tablet, Film Coated | XLCare Pharmaceuticals, Inc. | ANDA |
Frequently asked questions
What is rivaroxaban used for?
Rivaroxaban tablets are a factor Xa inhibitor indicated: to reduce the risk of major cardiovascular events in patients with coronary artery disease (CAD) ( 1.7 ) to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including patients after recent lower extremity revascularization due to symptomatic PAD ( 1.8 ) 1.7 Reduction of Risk of Major…
What are the side effects of rivaroxaban?
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 (… See the full label for the complete list.
Who makes rivaroxaban?
rivaroxaban is listed by 19 labelers in the FDA NDC directory, including Alembic Pharmaceuticals Inc., Alembic Pharmaceuticals Limited, Apotex Corp., Ascend Laboratories, LLC.