Xarelto Rivaroxaban Tablets Label Food And Drug
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HIGHLIGHTS OF PRESCRIBING INFORMATION -----------------------DOSAGE AND ADMINISTRATION---------------------- These highlights do not include all the information needed to use ! Nonvalvular Atrial Fibrillation: XARELTO® (rivaroxaban) safely and effectively. See full prescribing o For patients with CrCl >50 mL/min: 20 mg orally, once daily with information for XARELTO. the evening meal (2.1) o For patients with CrCl 15 - 50 mL/min: 15 mg orally, once daily XARELTO (rivaroxaban) tablets, for oral use with the evening meal (2.1) Initial U.S. Approval: 2011 o Avoid use in patients with CrCl <15 mL/min (2.3) ! Prophylaxis of DVT: 10 mg orally, once daily with or without food (2.2) WARNINGS: (A) DISCONTINUING XARELTO IN PATIENTS WITH ! Hepatic impairment (for nonvalvular AF and prophylaxis of DVT NONVALVULAR ATRIAL FIBRILLATION INCREASES RISK OF indications): STROKE, (B) SPINAL/EPIDURAL HEMATOMA o Avoid use in patients with moderate (Child-Pugh B) and severe See full prescribing information for complete boxed warning (Child-Pugh C) hepatic impairment or with any degree of hepatic disease associated with coagulopathy (2.3, 8.8)
A. DISCONTINUING XARELTO IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION --------------------DOSAGE FORMS AND STRENGTHS--------------------- Tablets: 10 mg, 15 mg, and 20 mg (3) Discontinuing XARELTO places patients at an increased risk of thrombotic events. If anticoagulation with XARELTO must be -------------------------------CONTRAINDICATIONS----------------------------- discontinued for a reason other than pathological bleeding, consider ! Active pathological bleeding (4) administering another anticoagulant (2.1, 5.1, 14.1). ! Severe hypersensitivity reaction to XARELTO (4) ---------------------------WARNINGS AND PRECAUTIONS------------------- B. SPINAL/EPIDURAL HEMATOMA ! Risk of bleeding: XARELTO can cause serious and fatal bleeding
Epidural or spinal hematomas have occurred in patients treated with Promptly evaluate signs and symptoms of blood loss. (5.2) XARELTO who are receiving neuraxial anesthesia or undergoing spinal ! Pregnancy related hemorrhage: Use XARELTO with caution in pregnant puncture. These hematomas may result in long-term or permanent women due to the potential for obstetric hemorrhage and/or emergent paralysis (5.2, 5.3, 6.2). delivery. Promptly evaluate signs and symptoms of blood loss. (5.4) ------------------------------ADVERSE REACTIONS----------------------------- Monitor patients frequently for signs and symptoms of neurological The most common adverse reaction (>5%) was bleeding. (6.1) impairment. If neurological compromise is noted, urgent treatment is necessary (5.3). To report SUSPECTED ADVERSE REACTIONS, contact Janssen Pharmaceuticals, Inc. at 1-800-526-7736 or FDA at 1-800-FDA-1088 or Consider the benefits and risks before neuraxial intervention in patients www.fda.gov/medwatch
anticoagulated or to be anticoagulated for thromboprophylaxis (5.3)
---------------------------------DRUG INTERACTIONS--------------------------- ----------------------------RECENT MAJOR CHANGES------------------------- ! Combined P-gp and strong CYP3A4 inhibitors and inducers: Avoid Boxed Warning 11/2011 concomitant use (7.1, 7.2) Indications and Usage (1.1) 11/2011 ! Prophylaxis of DVT: Dosage and Administration (2.1, 2.3) 11/2011 o Anticoagulants: Avoid concomitant use (7.3) Contraindications (4) 11/2011 -----------------------USE IN SPECIFIC POPULATIONS---------------------- Warnings and Precautions (5.1, 5.2, 5.5) 11/2011 ! Nursing mothers: discontinue drug or discontinue nursing (8.3) ----------------------------INDICATIONS AND USAGE-------------------------- ! Renal impairment: XARELTO is a factor Xa inhibitor indicated: o Prophylaxis of DVT: Avoid use in patients with severe impairment ! to reduce the risk of stroke and systemic embolism in patients with (CrCl <30 mL/min). Use with caution in moderate impairment nonvalvular atrial fibrillation (1.1) (CrCl 30 to <50 mL/min) (8.7) ! for the prophylaxis of deep vein thrombosis (DVT), which may lead to See 17 for PATIENT COUNSELING INFORMATION and Medication pulmonary embolism (PE) in patients undergoing knee or hip replacement Guide
surgery (1.2) Revised: 12/2011 7.1 Drugs that Inhibit Cytochrome P450 3A4 FULL PRESCRIBING INFORMATION: CONTENTS* Enzymes and Drug Transport Systems 7.2 Drugs that Induce Cytochrome P450 3A4 WARNINGS: (A) DISCONTINUING XARELTO IN Enzymes and Drug Transport Systems PATIENTS WITH NONVALVULAR ATRIAL 7.3 Anticoagulants FIBRILLATION INCREASES RISK OF STROKE, 7.4 NSAIDs/Aspirin (B) SPINAL/EPIDURAL HEMATOMA 7.5 Clopidogrel 1 INDICATIONS AND USAGE 7.6 Drug-Disease Interactions with Drugs that Inhibit 1.1 Reduction of Risk of Stroke and Systemic Cytochrome P450 3A4 Enzymes and Drug Embolism in Nonvalvular Atrial Fibrillation Transport Systems 1.2 Prophylaxis of Deep Vein Thrombosis 8 USE IN SPECIFIC POPULATIONS 2 DOSAGE AND ADMINISTRATION 8.1 Pregnancy 2.1 Nonvalvular Atrial Fibrillation 8.2 Labor and Delivery 2.2 Prophylaxis of Deep Vein Thrombosis 8.3 Nursing Mothers 2.3 General Dosing Instructions 8.4 Pediatric Use 3 DOSAGE FORMS AND STRENGTHS 8.5 Geriatric Use 4 CONTRAINDICATIONS 8.6 Females of Reproductive Potential 5 WARNINGS AND PRECAUTIONS 8.7 Renal Impairment 5.1 Increased Risk of Stroke after Discontinuation in 8.8 Hepatic Impairment Nonvalvular Atrial Fibrillation 10 OVERDOSAGE 5.2 Risk of Bleeding 11 DESCRIPTION 5.3 Spinal/Epidural Anesthesia or Puncture 12 CLINICAL PHARMACOLOGY 5.4 Risk of Pregnancy Related Hemorrhage 12.1 Mechanism of Action 5.5 Severe Hypersensitivity Reactions 12.2 Pharmacodynamics 6 ADVERSE REACTIONS 12.3 Pharmacokinetics 6.1 Clinical Trials Experience 12.6 QT/QTc Prolongation 6.2 Postmarketing Experience 13 NON-CLINICAL TOXICOLOGY 7 DRUG INTERACTIONS 1Reference ID: 3053960 13.1 Carcinogenesis, Mutagenesis, and Impairment of 17.1 Instructions for Patient Use Fertility 17.2 Bleeding Risks 14 CLINICAL STUDIES 17.3 Invasive or Surgical Procedures 14.1 Stroke Prevention in Nonvalvular Atrial Fibrillation 17.4 Concomitant Medication and Herbals 14.2 Prophylaxis of Deep Vein Thrombosis 17.5 Pregnancy and Pregnancy-Related Hemorrhage 16 HOW SUPPLIED/STORAGE AND HANDLING 17.6 Nursing 17 PATIENT COUNSELING INFORMATION 17.7 Females of Reproductive Potential *Sections or subsections omitted from the full prescribing information are not listed
2Reference ID: 3053960 FULL PRESCRIBING INFORMATION WARNINGS: (A) DISCONTINUING XARELTO IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION INCREASES RISK OF STROKE, (B) SPINAL/EPIDURAL HEMATOMA A. DISCONTINUING XARELTO IN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION Discontinuing XARELTO places patients at an increased risk of thrombotic events. An increased rate of stroke was observed following XARELTO discontinuation in clinical trials in atrial fibrillation patients. If anticoagulation with XARELTO must be discontinued for a reason other than pathological bleeding, consider administering another anticoagulant [see Dosage and Administration (2.1), Warnings and Precautions (5.1), and Clinical Studies (14.1)]
B. SPINAL/EPIDURAL HEMATOMA Epidural or spinal hematomas have occurred in patients treated with XARELTO 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 spinal deformity or spinal surgery [see Warnings and Precautions (5.2, 5.3) and Adverse Reactions (6.2)]
Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary [see Warnings and Precautions (5.3)]
Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis [see Warnings and Precautions (5.3)]
1 INDICATIONS AND USAGE 1.1 Reduction of Risk of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation XARELTO (rivaroxaban) is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation
3Reference ID: 3053960 There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled [see Clinical Studies (14.1)]
1.2 Prophylaxis of Deep Vein Thrombosis XARELTO (rivaroxaban) is indicated for the prophylaxis of deep vein thrombosis (DVT), which may lead to pulmonary embolism (PE) in patients undergoing knee or hip replacement surgery
2 DOSAGE AND ADMINISTRATION 2.1 Nonvalvular Atrial Fibrillation For patients with creatinine clearance (CrCl) >50 mL/min, the recommended dose of XARELTO is 20 mg taken orally once daily with the evening meal. For patients with CrCl 15 to 50 mL/min, the recommended dose is 15 mg once daily with the evening meal [see Use in Specific Populations (8.7)]
Switching from or to Warfarin - When switching patients from warfarin to XARELTO, discontinue warfarin and start XARELTO as soon as the International Normalized Ratio (INR) is below 3.0 to avoid periods of inadequate anticoagulation
No clinical trial data are available to guide converting patients from XARELTO to warfarin
XARELTO 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 XARELTO and begin both a parenteral anticoagulant and warfarin at the time the next dose of XARELTO would have been taken
Switching from or to Anticoagulants other than Warfarin - For patients currently receiving an anticoagulant other than warfarin, start XARELTO 0 to 2 hours prior to the next scheduled evening 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 XARELTO at the same time
For patients currently taking XARELTO and transitioning to an anticoagulant with rapid onset, discontinue XARELTO and give the first dose of the other anticoagulant (oral or parenteral) at the time that the next XARELTO dose would have been taken [see Drug Interactions (7.3)]
2.2 Prophylaxis of Deep Vein Thrombosis The recommended dose of XARELTO is 10 mg taken orally once daily with or without food
The initial dose should be taken at least 6 to 10 hours after surgery once hemostasis has been established
4Reference ID: 3053960 ! For patients undergoing hip replacement surgery, treatment duration of 35 days is recommended
! For patients undergoing knee replacement surgery, treatment duration of 12 days is recommended
2.3 General Dosing Instructions Hepatic Impairment No clinical data are available for patients with severe hepatic impairment. Avoid use of XARELTO in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment or with any hepatic disease associated with coagulopathy [see Use in Specific Populations (8.8)]
Renal Impairment Nonvalvular Atrial Fibrillation Avoid the use of XARELTO in patients with CrCl <15 mL/min. Periodically assess renal function as clinically indicated (i.e., more frequently in situations in which renal function may decline) and adjust therapy accordingly. Discontinue XARELTO in patients who develop acute renal failure while on XARELTO [see Use in Specific Populations (8.7)]
Prophylaxis of Deep Vein Thrombosis Avoid the use of XARELTO in patients with severe renal impairment (CrCl <30 mL/min) due to an expected increase in rivaroxaban exposure and pharmacodynamic effects in this patient population. Observe closely and promptly evaluate any signs or symptoms of blood loss in patients with moderate renal impairment (CrCl 30 to 50 mL/min). Patients who develop acute renal failure while on XARELTO should discontinue the treatment [see Use in Specific Populations (8.7)]
Surgery and Intervention If anticoagulation must be discontinued to reduce the risk of bleeding with surgical or other procedures, XARELTO should be stopped at least 24 hours before the procedure. In deciding whether a procedure should be delayed until 24 hours after the last dose of XARELTO, the increased risk of bleeding should be weighed against the urgency of intervention. XARELTO should be restarted after the surgical or other procedures as soon as adequate hemostasis has been established. If oral medication cannot be taken after surgical intervention, consider administering a parenteral anticoagulant
Missed Dose If a dose of XARELTO is not taken at the scheduled time, administer the dose as soon as possible on the same day
5Reference ID: 3053960 Use with P-gp and Strong CYP3A4 Inhibitors or Inducers Avoid concomitant use of XARELTO with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan) [see Drug Interactions (7.1)]
Avoid concomitant use of XARELTO with drugs that are combined P-gp and strong CYP3A4 inducers (e.g., carbamazepine, phenytoin, rifampin, St. John’s wort) [see Drug Interactions (7.2)]
3 DOSAGE FORMS AND STRENGTHS ! 10 mg tablets: Round, light red, biconvex and film-coated with a triangle pointing down above a “10” marked on one side and “Xa” on the other side ! 15 mg tablets: Round, red, biconvex, and film-coated with a triangle pointing down above a “15” marked on one side and “Xa” on the other side ! 20 mg tablets: Triangle-shaped, dark red, and film-coated with a triangle pointing down above a “20” marked on one side and “Xa” on the other side 4 CONTRAINDICATIONS XARELTO is contraindicated in patients with: ! active pathological bleeding [see Warnings and Precautions (5.2)] ! severe hypersensitivity reaction to XARELTO [see Warnings and Precautions (5.5)] 5 WARNINGS AND PRECAUTIONS 5.1 Increased Risk of Stroke after Discontinuation in Nonvalvular Atrial Fibrillation Discontinuing XARELTO in the absence of adequate alternative anticoagulation increases the risk of thrombotic events. An increased rate of stroke was observed during the transition from XARELTO to warfarin in clinical trials in atrial fibrillation patients. If XARELTO must be discontinued for a reason other than pathological bleeding, consider administering another anticoagulant [see Dosage and Administration (2.1) and Clinical Studies (14.1)]
5.2 Risk of Bleeding XARELTO increases the risk of bleeding and can cause serious or fatal bleeding. In deciding whether to prescribe XARELTO 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. Discontinue XARELTO in patients with active pathological hemorrhage
6Reference ID: 3053960 A specific antidote for rivaroxaban is not available. Because of high plasma protein binding, rivaroxaban is not expected to be dialyzable [see Clinical Pharmacology (12.3)]. Protamine sulfate and vitamin K are not expected to affect the anticoagulant activity of rivaroxaban. There is no experience with antifibrinolytic agents (tranexamic acid, aminocaproic acid) in individuals receiving rivaroxaban. There is neither scientific rationale for benefit nor experience with systemic hemostatics (desmopressin and aprotinin) in individuals receiving rivaroxaban. Use of procoagulant reversal agents such as prothrombin complex concentrate (PCC), activated prothrombin complex concentrate (APCC), or recombinant factor VIIa (rFVIIa) may be considered, but has not been evaluated in clinical trials
Concomitant use of drugs affecting hemostasis increases the risk of bleeding. These include aspirin, P2Y12 platelet inhibitors, other antithrombotic agents, fibrinolytic therapy, and non steroidal anti-inflammatory drugs (NSAIDs) [see Drug Interactions (7.3), (7.4), (7.5)]
Concomitant use of drugs that are combined P-gp and CYP3A4 inhibitors (e.g. ketoconazole and ritonavir) increases rivaroxaban exposure and may increase bleeding risk [see Drug Interactions (7.1)]
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]
An epidural catheter should not be removed earlier than 18 hours after the last administration of XARELTO. The next XARELTO dose is not to be administered earlier than 6 hours after the removal of the catheter. If traumatic puncture occurs, the administration of XARELTO is to be delayed for 24 hours
5.4 Risk of Pregnancy Related Hemorrhage XARELTO should be used with caution in pregnant women and only if the potential benefit justifies the potential risk to the mother and fetus. XARELTO dosing in pregnancy has not been studied. The anticoagulant effect of XARELTO cannot be monitored with standard laboratory testing nor readily reversed. Promptly evaluate any signs or symptoms suggesting blood loss (e.g., a drop in hemoglobin and/or hematocrit, hypotension, or fetal distress)
7Reference ID: 3053960 5.5 Severe Hypersensitivity Reactions There were postmarketing cases of anaphylaxis in patients treated with XARELTO to reduce the risk of DVT. Patients who have a history of a severe hypersensitivity reaction to XARELTO should not receive XARELTO [see Adverse Reactions (6.2)]
6 ADVERSE REACTIONS 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, 11598 patients were exposed to XARELTO. These included 7111 patients who received XARELTO 15 mg or 20 mg orally once daily for a mean of 19 months (5558 for 12 months and 2512 for 24 months) to reduce the risk of stroke and systemic embolism in nonvalvular atrial fibrillation (ROCKET AF) and 4487 patients who received XARELTO 10 mg orally once daily for prophylaxis of DVT following hip or knee replacement surgery (RECORD 1-3)
Hemorrhage The most common adverse reactions with XARELTO 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 XARELTO vs. 3.1% for warfarin. The incidence of discontinuations for non-bleeding adverse events was similar in both treatment groups
Table 1 shows the number of patients experiencing various types of bleeding events in the ROCKET AF study
8Reference ID: 3053960 Table 1: Bleeding Events in ROCKET AF* Parameter XARELTO Event Rate Warfarin Event Rate N = 7111 (per 100 Pt-yrs) N = 7125 (per 100 Pt-yrs) n (%) n (%) Major bleeding† 395 (5.6) 3.6 386 (5.4) 3.5 ‡ Bleeding into a critical organ 91 (1.3) 0.8 133 (1.9) 1.2 Fatal bleeding 27 (0.4) 0.2 55 (0.8) 0.5 Bleeding resulting in transfusion 183 (2.6) 1.7 149 (2.1) 1.3 of ≥ 2 units of whole blood or packed red blood cells Gastrointestinal bleeding 221 (3.1) 2.0 140 (2.0) 1.2 * For all sub-types of major bleeding, single events may be represented in more than one row, and individual patients may have more than one event
† Defined as clinically overt bleeding associated with a decrease in hemoglobin of ≥ 2 g/dL, transfusion of ≥ 2 units of packed red blood cells or whole blood, bleeding at a critical site, or with a fatal outcome. Hemorrhagic strokes are counted as both bleeding and efficacy events. Major bleeding rates excluding strokes are 3.3 per 100 Pt-yrs for XARELTO vs. 2.9 per 100 Pt-yrs for warfarin
‡ The majority of the events were intracranial, and also included intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal
Prophylaxis of Deep Vein Thrombosis In the RECORD clinical trials, the overall incidence rate of adverse reactions leading to permanent treatment discontinuation was 3.7% with XARELTO
The mean duration of XARELTO treatment was 11.9 days in the total knee replacement study and 33.4 days in the total hip replacement studies. Overall, in the RECORD program, the mean age of the patients studied in the XARELTO group was 64 years, 59% were female and 82% were Caucasian. Twenty-seven percent (1206) of patients underwent knee replacement surgery and 73% (3281) underwent hip replacement surgery
The rates of major bleeding events and any bleeding events observed in patients in the RECORD clinical trials are shown in Table 2
9Reference ID: 3053960 Table 2: Bleeding Events* in Patients Undergoing Hip or Knee Replacement Surgeries (RECORD 1-3) XARELTO 10 mg Enoxaparin† Total treated patients N = 4487 N = 4524 n (%) n (%) Major bleeding event 14 (0.3) 9 (0.2) Fatal bleeding 1 (<0.1) 0 Bleeding into a critical organ 2 (<0.1) 3 (0.1) Bleeding that required re-operation 7 (0.2) 5 (0.1) Extra-surgical site bleeding 4 (0.1) 1 (<0.1) requiring transfusion of >2 units of whole blood or packed cells Any bleeding event‡ 261 (5.8) 251 (5.6) Hip Surgery Studies N = 3281 N = 3298 n (%) n (%) Major bleeding event 7 (0.2) 3 (0.1) Fatal bleeding 1 (<0.1) 0 Bleeding into a critical organ 1 (<0.1) 1 (<0.1) Bleeding that required re-operation 2 (0.1) 1 (<0.1) Extra-surgical site bleeding 3 (0.1) 1 (<0.1) requiring transfusion of >2 units of whole blood or packed cells Any bleeding event‡ 201 (6.1) 191 (5.8) Knee Surgery Study N = 1206 N = 1226 n (%) n (%) Major bleeding event 7 (0.6) 6 (0.5) Fatal bleeding 0 0 Bleeding into a critical organ 1 (0.1) 2 (0.2) Bleeding that required re-operation 5 (0.4) 4 (0.3) Extra-surgical site bleeding 1 (0.1) 0 requiring transfusion of >2 units of whole blood or packed cells Any bleeding event‡ 60 (5.0) 60 (4.9) * Bleeding events occurring any time following the first dose of double-blind study medication (which may have been prior to administration of active drug) until two days after the last dose of double-blind study medication. Patients may have more than one event
† Includes the placebo-controlled period for RECORD 2, enoxaparin dosing was 40 mg once daily (RECORD 1-3) ‡ Includes major bleeding events Following XARELTO treatment, the majority of major bleeding complications (≥60%) occurred during the first week after surgery
Other Adverse Reactions Non-hemorrhagic adverse drug reactions (ADRs) reported in ≥1% of XARELTO-treated patients are shown in Table 3
10Reference ID: 3053960 Table 3: Other Adverse Drug Reactions* Reported by ≥1% of XARELTO-Treated Patients in RECORD 1-3 Studies System/Organ Class XARELTO Enoxaparin† Adverse Reaction 10 mg (N = 4487) (N = 4524) n (%) n (%) Injury, poisoning and procedural complications Wound secretion 125 (2.8) 89 (2.0) Musculoskeletal and connective tissue disorders Pain in extremity 74 (1.7) 55 (1.2) Muscle spasm 52 (1.2) 32 (0.7) Nervous system disorders Syncope 55 (1.2) 32 (0.7) Skin and subcutaneous tissue disorders Pruritus 96 (2.1) 79 (1.8) Blister 63 (1.4) 40 (0.9) * ADR occurring any time following the first dose of double-blind medication, which may have been prior to administration of active drug, until two days after the last dose of double-blind study medication
† Includes the placebo-controlled period of RECORD 2, enoxaparin dosing was 40 mg once daily (RECORD 1-3) Other clinical trial experience: In an investigational study of acute medically ill patients being treated with XARELTO 10 mg tablets, cases of pulmonary hemorrhage and pulmonary hemorrhage with bronchiectasis were observed
6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of rivaroxaban
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure
Blood and lymphatic system disorders: agranulocytosis Gastrointestinal disorders: retroperitoneal hemorrhage Hepatobiliary disorders: jaundice, cholestasis, cytolytic hepatitis Immune system disorders: hypersensitivity, anaphylactic reaction, anaphylactic shock Nervous system disorders: cerebral hemorrhage, subdural hematoma, epidural hematoma, hemiparesis Skin and subcutaneous tissue disorders: Stevens-Johnson syndrome 11Reference ID: 3053960 7 DRUG INTERACTIONS Rivaroxaban is a substrate of CYP3A4/5, CYP2J2, and the P-gp and ATP-binding cassette G2 (ABCG2) transporters. Inhibitors and inducers of these CYP450 enzymes or transporters (e.g., P-gp) may result in changes in rivaroxaban exposure
7.1 Drugs that Inhibit Cytochrome P450 3A4 Enzymes and Drug Transport Systems In drug interaction studies evaluating the concomitant use with drugs that are combined P-gp and CYP3A4 inhibitors, increases in rivaroxaban exposure and pharmacodynamic effects (i.e., factor Xa inhibition and PT prolongation) were observed. Significant increases in rivaroxaban exposure may increase bleeding risk
! Ketoconazole (combined P-gp and strong CYP3A4 inhibitor): Steady-state rivaroxaban AUC and Cmax increased by 160% and 70%, respectively. Similar increases in pharmacodynamic effects were also observed
! Ritonavir (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 150% and 60%, respectively. Similar increases in pharmacodynamic effects were also observed
! Clarithromycin (combined P-gp and strong CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 50% and 40%, respectively. The smaller increases in exposure observed for clarithromycin compared to ketoconazole or ritonavir may be due to the relative difference in P-gp inhibition
! Erythromycin (combined P-gp and moderate CYP3A4 inhibitor): Both the single-dose rivaroxaban AUC and Cmax increased by 30%
! Fluconazole (moderate CYP3A4 inhibitor): Single-dose rivaroxaban AUC and Cmax increased by 40% and 30%, respectively
Avoid concomitant administration of XARELTO with combined P-gp and strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, lopinavir/ritonavir, ritonavir, indinavir/ritonavir, and conivaptan), which cause significant increases in rivaroxaban exposure that may increase bleeding risk
12Reference ID: 3053960
: 10 mg orally, once daily with or without food (2.2) ! Hepatic impairment (for nonvalvular AF and prophylaxis of DVT indications): o Avoid use in patients with moderate (Child-Pugh B) and …
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Frequently Asked Questions
What are the strengths and packages of xarelto rivaroxaban?
XARELTO 2.5 mg and 10 mg tablets can be taken with or without food. For the 20 mg dose in the fasted state, the absolute bioavailability is approximately 66%. Coadministration of XARELTO with food increases the bioavailability of the 20 mg dose (mean AUC and Cmax increasing by 39% and 76% respectively with food).
Can you take xarelto with food?
If you have CAD or PAD, Xarelto (rivaroxaban) should be taken together with low-dose aspirin (75 mg to 100 mg) to lower your risk of serious heart-related problems. Discuss with your provider if you're unsure if you should be taking aspirin. Prices for Xarelto (rivaroxaban) start at just $ 520.72 with a GoodRx coupon.
Can i take aspirin with xarelto rivaroxaban?
Xarelto belongs to a class of drugs called Anticoagulants, Cardiovascular; Anticoagulants, Hematologic; Factor Xa Inhibitors. It is not known if Xarelto is safe and effective in children. What are the possible side effects of Xarelto? easy bruising or bleeding (nosebleeds, bleeding gums, heavy menstrual bleeding),