Xarelto

Description

Rivaroxaban, a factor Xa (FXa) inhibitor, is the active ingredient in XARELTO Tablets and XARELTO for oral suspension. The chemical name of rivaroxaban is 5-Chloro-N-({(5S)-2-oxo-3-4-(3-oxo-4-morpholinyl)phenyl-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide. Its molecular formula is C19H18ClN3O5S, and it has a molecular weight of 435.89. Rivaroxaban is a pure (S)-enantiomer and is characterized as an odorless, non-hygroscopic, white to yellowish powder. It is only slightly soluble in organic solvents, such as acetone and polyethylene glycol 400, and is practically insoluble in water and aqueous media.

Each XARELTO tablet contains 2.5 mg, 10 mg, 15 mg, or 20 mg of rivaroxaban. The inactive ingredients in XARELTO tablets include croscarmellose sodium, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and sodium lauryl sulfate. XARELTO for oral suspension is supplied as granules in bottles containing 155 mg of rivaroxaban, which provides 1 mg of rivaroxaban per mL after reconstitution. The inactive ingredients in XARELTO for oral suspension consist of anhydrous citric acid, hypromellose, mannitol, microcrystalline cellulose and carboxymethylcellulose sodium, sodium benzoate, sucralose, sweet and creamy flavor, and xanthan gum.

Uses and Indications

XARELTO is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is also indicated for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). Additionally, XARELTO is indicated for the reduction in the risk of recurrence of DVT or PE.

For patients undergoing knee or hip replacement surgery, XARELTO is indicated for the prophylaxis of DVT, which may lead to PE. It is further indicated for the prophylaxis of venous thromboembolism (VTE) in acutely ill medical patients.

In patients with coronary artery disease (CAD), XARELTO is indicated to reduce the risk of major cardiovascular events. It is also indicated to reduce the risk of major thrombotic vascular events in patients with peripheral artery disease (PAD), including those who have recently undergone lower extremity revascularization due to symptomatic PAD.

XARELTO is indicated for the treatment of VTE and the reduction in the risk of recurrent VTE in pediatric patients from birth to less than 18 years of age. Furthermore, it is indicated for thromboprophylaxis in pediatric patients aged 2 years and older with congenital heart disease following the Fontan procedure.

Dosage and Administration

For the management of nonvalvular atrial fibrillation, the recommended dosage is 15 mg or 20 mg administered once daily with food.

In the treatment of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), the initial dosage is 15 mg orally twice daily with food for the first 21 days. Following this period, the dosage should be adjusted to 20 mg orally once daily with food for the remainder of the treatment.

To reduce the risk of recurrence of DVT and/or PE in patients who remain at risk, a dosage of 10 mg once daily is recommended, which can be taken with or without food, after a minimum of 6 months of standard anticoagulant therapy.

For the prophylaxis of DVT following hip or knee replacement surgery, the recommended dosage is 10 mg orally once daily, which may be taken with or without food.

In acutely ill medical patients at risk for thromboembolic complications but not at high risk of bleeding, a dosage of 10 mg once daily is advised, with or without food, during hospitalization and after discharge, for a total duration of 31 to 39 days.

For patients with coronary artery disease (CAD) or peripheral artery disease (PAD), the recommended dosage is 2.5 mg orally twice daily with or without food, in conjunction with aspirin at a dosage of 75–100 mg once daily.

For pediatric patients, healthcare professionals should refer to the dosing recommendations provided in the Full Prescribing Information.

Contraindications

Use of this product is contraindicated in patients with active pathological bleeding due to the risk of exacerbating the condition. Additionally, it is contraindicated in individuals with a severe hypersensitivity reaction to XARELTO, as this may lead to serious adverse effects.

Warnings and Precautions

XARELTO (rivaroxaban) carries significant warnings that healthcare professionals must consider to ensure patient safety.

Risk of Bleeding XARELTO is associated with a risk of serious and potentially fatal bleeding. It is essential to be aware that an agent to reverse the activity of rivaroxaban is available for emergency situations.

Pregnancy-Related Hemorrhage Caution is advised when prescribing XARELTO to pregnant women due to the potential for obstetric hemorrhage and the risk of complications during emergent delivery.

Prosthetic Heart Valves The use of XARELTO is not recommended in patients with prosthetic heart valves, as the safety and efficacy in this population have not been established.

Increased Risk of Thrombosis Patients with triple positive antiphospholipid syndrome are at an increased risk of thrombosis, and the use of XARELTO in this group is not recommended.

Premature Discontinuation Premature discontinuation of XARELTO significantly increases the risk of thrombotic events. It is critical to consider transitioning to another anticoagulant if XARELTO is discontinued for reasons other than pathological bleeding or the completion of a prescribed therapy course.

Epidural or Spinal Hematomas There is a risk of epidural or spinal hematomas in patients receiving XARELTO who are undergoing neuraxial anesthesia or spinal puncture. Such hematomas can lead to long-term or permanent paralysis. Healthcare providers should monitor patients closely for signs and symptoms of neurological impairment and respond urgently if any are observed. A careful assessment of the benefits and risks is necessary before proceeding with neuraxial interventions in patients who are or may need to be anticoagulated.

In summary, healthcare professionals must remain vigilant regarding the potential risks associated with XARELTO, particularly concerning bleeding, thrombosis, and the implications of neuraxial procedures.

Side Effects

The most common adverse reactions observed in adult patients receiving XARELTO include bleeding, which occurs in more than 5% of patients. In pediatric patients, bleeding is reported in over 10% of cases, along with other reactions such as cough, vomiting, and gastroenteritis.

Serious warnings associated with XARELTO include the risk of thrombotic events upon premature discontinuation of the medication. Additionally, there is a significant risk of spinal or epidural hematomas in patients undergoing neuraxial anesthesia or spinal puncture, which may lead to long-term or permanent paralysis. It is crucial to monitor patients closely for any signs or symptoms of neurological impairment and to provide urgent treatment if such symptoms arise.

Clinical trial data indicate that hemorrhage is the most frequently reported adverse reaction associated with XARELTO. In the context of nonvalvular atrial fibrillation, bleeding events were the leading cause of permanent drug discontinuation, occurring in 4.3% of patients on XARELTO compared to 3.1% in those treated with warfarin.

In the ROCKET AF trial, major bleeding events were reported in 3.6% of patients receiving XARELTO, compared to 3.5% for warfarin. Specific types of bleeding included intracranial hemorrhage (0.5% for XARELTO vs. 0.7% for warfarin), hemorrhagic stroke (0.3% for XARELTO vs. 0.5% for warfarin), and gastrointestinal bleeding (2.0% for XARELTO vs. 1.2% for warfarin). Fatal bleeding occurred in 0.2% of patients on XARELTO, compared to 0.5% for warfarin.

Additional studies, including the EINSTEIN DVT and PE studies, reported that bleeding events were the most common adverse reactions leading to permanent drug discontinuation, with rates of 1.7% for XARELTO versus 1.5% for enoxaparin/VKA. The MAGELLAN study also noted bleeding events as the primary reason for discontinuation, occurring in 2.5% of patients on XARELTO compared to 1.4% for enoxaparin/placebo. In the COMPASS trial, the rate was 2.7% for XARELTO 2.5 mg twice daily versus 1.2% for placebo.

Other adverse reactions reported in the EINSTEIN DVT study included abdominal pain (2.7% for XARELTO vs. 1.5% for enoxaparin/VKA), fatigue (1.4% for XARELTO vs. 0.9% for enoxaparin/VKA), back pain (2.9% for XARELTO vs. 1.8% for enoxaparin/VKA), dizziness (2.2% for XARELTO vs. 1.3% for enoxaparin/VKA), anxiety (1.4% for XARELTO vs. 0.6% for enoxaparin/VKA), depression (1.2% for XARELTO vs. 0.6% for enoxaparin/VKA), and insomnia (1.6% for XARELTO vs. 1.1% for enoxaparin/VKA).

Drug Interactions

Concomitant use of strong P-glycoprotein (P-gp) inhibitors and inducers with this medication should be avoided due to the potential for significant drug interactions. These interactions may alter the pharmacokinetics of the medication, leading to either increased toxicity or reduced efficacy.

Additionally, the use of anticoagulants alongside this medication is not recommended. The combination may increase the risk of bleeding or other adverse effects, necessitating careful consideration and monitoring if such combinations are deemed necessary.

Healthcare professionals should assess the need for dosage adjustments or enhanced monitoring protocols when managing patients on this medication who are also receiving drugs from these categories.

Packaging & NDC

The table below lists all NDC Code configurations of Xarelto (rivaroxaban), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of XARELTO have been established in pediatric patients from birth to less than 18 years for the treatment of venous thromboembolism (VTE) and the reduction in the risk of recurrent VTE. This use is supported by evidence from adequate and well-controlled studies in adults, along with additional pharmacokinetic, safety, and efficacy data from a multicenter, prospective, open-label, active-controlled randomized study involving 500 pediatric patients in the specified age range.

XARELTO has been shown to be safe and effective for pediatric patients aged 2 years and older with congenital heart disease who have undergone the Fontan procedure. This indication is further supported by data from a multicenter, prospective, open-label, active-controlled study involving 112 pediatric patients, which evaluated the pharmacokinetic properties and the safety and efficacy of XARELTO for thromboprophylaxis over 12 months in children with single ventricle physiology post-Fontan procedure.

Dosing for XARELTO in pediatric patients is available for 10 mg, 15 mg, and 20 mg tablets, with clinical studies supporting their use. However, there are no safety, efficacy, pharmacokinetic, or pharmacodynamic data to support the use of XARELTO 2.5 mg tablets in pediatric patients; therefore, these tablets are not recommended for this population.

It is important to note that XARELTO has not been studied in children less than 6 months who were born at less than 37 weeks of gestation, had less than 10 days of oral feeding, or had a body weight of less than 2.6 kg, and thus dosing cannot be reliably determined or recommended for these patients. Although not all adverse reactions identified in the adult population have been observed in clinical trials involving children and adolescents, the same warnings and precautions applicable to adults should be considered for pediatric patients.

Geriatric Use

Elderly patients, defined as those aged 65 years and older, comprised 64 percent of the total adult population (N=64,943 patients) in clinical trials for the approved indications of XARELTO, with 27 percent of these patients being 75 years and older. The efficacy of XARELTO in geriatric patients was found to be comparable to that observed in patients younger than 65 years.

However, it is important to note that both thrombotic and bleeding event rates were higher in elderly patients. Therefore, healthcare providers should exercise caution when prescribing XARELTO to this population. Close monitoring for adverse events is recommended, and consideration should be given to potential dose adjustments based on individual patient factors, including renal function and the presence of concomitant medications that may increase the risk of bleeding.

Pregnancy

The available data on XARELTO (rivaroxaban) in pregnant women are limited and insufficient to establish a drug-associated risk of adverse developmental outcomes. Caution is advised when prescribing XARELTO to pregnant patients due to the potential for pregnancy-related hemorrhage and/or emergent delivery. The anticoagulant effect of XARELTO cannot be reliably monitored with standard laboratory testing, necessitating careful consideration of the benefits and risks for both the mother and the fetus.

Adverse outcomes in pregnancy can occur regardless of maternal health or medication use. The estimated background risk of major birth defects and miscarriage in the U.S. general population is approximately 2–4% and 15–20%, respectively. Pregnancy itself is a known risk factor for venous thromboembolism, with an increased risk in women with inherited or acquired thrombophilias. Pregnant women with thromboembolic disease face heightened risks of maternal complications, including pre-eclampsia, as well as increased risks for intrauterine growth restriction, placental abruption, and early and late pregnancy loss.

Given the pharmacologic activity of Factor Xa inhibitors and the potential for placental transfer, there is a risk of bleeding occurring at any site in the fetus and/or neonate. All patients receiving anticoagulants, including pregnant women, are at risk for bleeding, which may be exacerbated during labor or delivery. The risk of bleeding must be carefully balanced against the risk of thrombotic events when considering the use of XARELTO in this population.

There are no adequate or well-controlled studies of XARELTO in pregnant women, and dosing for this population has not been established. Post-marketing experience has not provided sufficient data to determine a rivaroxaban-associated risk for major birth defects or miscarriage. Animal studies indicate that rivaroxaban crosses the placenta, with evidence of increased fetal toxicity, including increased resorptions, decreased numbers of live fetuses, and reduced fetal body weight in rabbits at doses corresponding to approximately four times the human exposure based on AUC comparisons. In rats, significant fetal body weight reductions and maternal and fetal deaths were observed at doses corresponding to about 14 times and six times the maximum human exposure, respectively.

Lactation

Rivaroxaban has been detected in human milk. However, there are insufficient data to determine the effects of rivaroxaban on breastfed infants or on milk production. In animal studies, rivaroxaban and/or its metabolites were present in the milk of lactating rats. Following a single oral administration of 3 mg/kg of radioactive ^14C-rivaroxaban to lactating rats between Day 8 to 10 postpartum, the concentration of total radioactivity was measured in milk samples collected up to 32 hours post-dose. The estimated amount of radioactivity excreted in milk within 32 hours after administration was 2.1% of the maternal dose.

The developmental and health benefits of breastfeeding should be considered alongside the mother's clinical need for rivaroxaban and any potential adverse effects on the breastfed infant from rivaroxaban or from the underlying maternal condition.

Renal Impairment

In pharmacokinetic studies, patients with renal impairment exhibited an increase in rivaroxaban exposure by approximately 44 to 64% compared to healthy adult subjects with normal creatinine clearance. This increase was accompanied by heightened pharmacodynamic effects. In the ROCKET AF trial, patients with creatinine clearance (CrCl) between 30 to 50 mL/min received XARELTO 15 mg once daily, resulting in serum concentrations and clinical outcomes comparable to those of patients with better renal function receiving XARELTO 20 mg once daily. Although patients with CrCl <30 mL/min were not studied, it is anticipated that administering XARELTO 15 mg once daily in this population will yield similar serum concentrations to those seen in patients with moderate renal impairment.

Clinical efficacy and safety studies did not include patients with end-stage renal disease (ESRD) on dialysis. However, in patients with ESRD maintained on intermittent hemodialysis, a dose of XARELTO 15 mg once daily is expected to produce rivaroxaban concentrations and pharmacodynamic activity akin to those observed in the ROCKET AF study. The implications for stroke reduction and bleeding risk in this population remain uncertain.

In the EINSTEIN trials, patients with CrCl <30 mL/min were excluded, but it is expected that administering XARELTO in this group will result in serum concentrations similar to those in patients with moderate renal impairment (CrCl 30 to <50 mL/min). Close monitoring for signs or symptoms of blood loss is advised for patients with CrCl 15 to <30 mL/min, and XARELTO should be avoided in those with CrCl <15 mL/min.

The combined analysis of the RECORD 1–3 clinical efficacy studies indicated no increased bleeding risk for patients with CrCl 30 to 50 mL/min, although a potential increase in total venous thromboemboli was noted. Patients with CrCl <30 mL/min were excluded from these trials, but a dose of XARELTO 10 mg once daily is expected to yield serum concentrations similar to those in patients with moderate renal impairment. Similar precautions regarding blood loss monitoring apply to this group.

In the MAGELLAN study, patients with CrCl <30 mL/min were also excluded. For those in this category, a dose of XARELTO 10 mg once daily is anticipated to produce serum concentrations akin to those in patients with moderate renal impairment. Monitoring for blood loss is essential for patients with CrCl 15 to <30 mL/min, and XARELTO should not be used in patients with CrCl <15 mL/min.

Limited data exist for patients with CrCl <30 mL/min in the COMPASS and VOYAGER studies, where patients with CrCl <15 mL/min were excluded. In patients with CrCl <30 mL/min, a dose of 2.5 mg XARELTO twice daily is expected to provide exposure similar to that in patients with moderate renal impairment, whose efficacy and safety outcomes were comparable to those with preserved renal function. No clinical outcome data are available for the use of XARELTO with aspirin in patients with ESRD on dialysis, as these patients were not enrolled in the COMPASS or VOYAGER studies. In patients with ESRD on intermittent hemodialysis, a dose of XARELTO 2.5 mg twice daily is expected to yield concentrations and pharmacodynamic activity similar to those observed in moderate renal impairment patients in the COMPASS study, though the effects on cardiovascular risk reduction and bleeding risk remain unknown.

No dosage adjustment is necessary for patients aged 1 year or older with mild renal impairment (eGFR 50 to ≤ 80 mL/min/1.73 m²). Due to limited clinical data, the use of XARELTO is not recommended in pediatric patients aged 1 year or older with moderate or severe renal impairment (eGFR <50 mL/min/1.73 m²) or in those younger than 1 year with serum creatinine levels above the 97.5th percentile.

Hepatic Impairment

Patients with hepatic impairment may experience significant alterations in the pharmacokinetics of XARELTO. In a pharmacokinetic study, adult subjects with moderate hepatic impairment (Child-Pugh B) exhibited an increase in the area under the curve (AUC) by 127% compared to healthy adult subjects with normal liver function. Due to these findings, the use of XARELTO is contraindicated in patients with moderate (Child-Pugh B) and severe (Child-Pugh C) hepatic impairment, as well as in those with any hepatic disease associated with coagulopathy.

Furthermore, the safety and pharmacokinetics of XARELTO have not been evaluated in patients with severe hepatic impairment (Child-Pugh C). It is important to note that no clinical data are available regarding the use of XARELTO in pediatric patients with hepatic impairment. Therefore, careful consideration and monitoring are advised when assessing treatment options for patients with compromised liver function.

Overdosage

In the event of an overdose of XARELTO, healthcare professionals should be aware that the primary concern is the potential for hemorrhage. If bleeding complications arise, it is imperative to discontinue XARELTO and initiate appropriate therapeutic measures to manage the situation effectively.

Rivaroxaban, the active ingredient in XARELTO, exhibits limited absorption at single doses exceeding 50 mg, which means that systemic exposure does not increase significantly beyond this threshold. In cases of overdose, the administration of activated charcoal may be considered to reduce further absorption of the drug.

It is important to note that due to rivaroxaban's high plasma protein binding, the drug is not amenable to dialysis. Therefore, alternative management strategies must be employed. Partial reversal of laboratory anticoagulation parameters can be achieved through the use of plasma products, which may assist in mitigating the effects of the overdose.

Additionally, there is an available agent specifically designed to reverse the anti-factor Xa activity of rivaroxaban. This agent can be utilized as part of the management protocol for patients experiencing an overdose, providing an important tool in the clinical setting.

Nonclinical Toxicology

Rivaroxaban was evaluated for its carcinogenic potential in long-term studies involving oral gavage administration to mice and rats for a duration of up to 2 years. The results indicated that rivaroxaban did not exhibit carcinogenic properties in either species. At the highest tested dose of 60 mg/kg/day, systemic exposures (AUCs) of unbound rivaroxaban in male and female mice were found to be 1- and 2-fold, respectively, compared to the human exposure at a dose of 20 mg/day. In male and female rats, systemic exposures at the same highest dose were 2- and 4-fold, respectively, greater than the human exposure.

In terms of mutagenicity, rivaroxaban demonstrated no mutagenic effects in bacterial assays (Ames test) and was not found to be clastogenic in V79 Chinese hamster lung cells in vitro. Additionally, results from the mouse micronucleus test in vivo confirmed the absence of mutagenic activity.

Assessment of reproductive toxicity revealed no impairment of fertility in male or female rats administered rivaroxaban at doses up to 200 mg/kg/day. This dosage resulted in exposure levels, based on the unbound AUC, that were at least 13 times higher than those observed in humans receiving a daily dose of 20 mg rivaroxaban.

Postmarketing Experience

During post-approval use of XARELTO, the following adverse reactions have been identified. These reactions were reported voluntarily from a population of uncertain size, making it challenging to reliably estimate their frequency or establish a causal relationship to drug exposure.

Blood and lymphatic system disorders include agranulocytosis and thrombocytopenia.

Hepatobiliary disorders reported are jaundice, cholestasis, and hepatitis, which encompasses hepatocellular injury.

Immune system disorders consist of hypersensitivity, anaphylactic reaction, anaphylactic shock, and angioedema.

Nervous system disorders include hemiparesis.

Renal disorders reported include anticoagulant-related nephropathy.

Respiratory, thoracic, and mediastinal disorders feature eosinophilic pneumonia.

Skin and subcutaneous tissue disorders include Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS).

Injury, poisoning, and procedural complications include atraumatic splenic rupture.

Patient Counseling

Healthcare providers should advise patients and/or caregivers to read the FDA-approved patient labeling (Medication Guide) thoroughly. It is essential to instruct patients to take XARELTO only as directed and to emphasize that they should not discontinue the medication without first consulting their healthcare professional.

For patients with atrial fibrillation, it is important to recommend taking XARELTO once daily with the evening meal. Patients undergoing initial treatment for deep vein thrombosis (DVT) and/or pulmonary embolism (PE) should be advised to take XARELTO 15 mg or 20 mg tablets with food at approximately the same time every day. For those at continued risk of recurrent DVT and/or PE after at least six months of initial treatment, a dosage of 10 mg once daily with or without food is recommended.

Patients who have difficulty swallowing the tablet whole should be instructed to crush XARELTO and mix it with a small amount of applesauce, followed by food. For patients requiring an NG tube or gastric feeding tube, caregivers should crush the XARELTO tablet and mix it with a small amount of water before administering it via the tube.

In the event of a missed dose, healthcare providers should advise patients to follow the instructions in the Full Prescribing Information based on their specific dosing schedule. For pediatric patients, the adult caregiver should administer the dose using the syringes provided in the original carton and should be informed whether the dose needs to be taken with food. It is crucial to advise caregivers that the tablet must not be split to provide a fraction of a tablet dose. If a child vomits or spits up the dose within 30 minutes after administration, a new dose should be given. However, if vomiting occurs more than 30 minutes after the dose, the caregiver should not re-administer the dose and should continue with the next scheduled dose. Caregivers should be instructed to contact the child's doctor if vomiting or spitting up occurs repeatedly. For children unable to swallow whole tablets, XARELTO oral suspension may be utilized.

Patients should be advised to report any unusual bleeding or bruising to their physician, as it may take longer than usual to stop bleeding, and they may experience increased bruising and bleeding while on XARELTO. If patients have undergone neuraxial anesthesia or spinal puncture, particularly if they are taking concomitant NSAIDs or platelet inhibitors, they should be vigilant 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. Patients experiencing any of these symptoms should contact their physician immediately.

Patients must inform their healthcare professional that they are taking XARELTO before any invasive procedures, including dental work. They should also disclose to their physicians and dentists any prescription or over-the-counter medications or herbal supplements they are taking or plan to take, allowing for an evaluation of potential interactions.

Women who become pregnant or intend to become pregnant during treatment with XARELTO should inform their physician immediately. Pregnant women receiving XARELTO should report any bleeding or symptoms of blood loss to their physician without delay. Patients should discuss the benefits and risks of XARELTO for both the mother and child if they are nursing or plan to nurse during anticoagulant treatment. Additionally, patients who can become pregnant should engage in discussions about pregnancy planning with their physician.

Storage and Handling

The product is supplied in a configuration that includes a reconstituted suspension. It is essential to discard the reconstituted suspension after the "Discard after" date indicated on the bottle.

Storage conditions require the product to be maintained at room temperature, specifically between 20 °C to 25 °C (68 °F to 77 °F). Temporary excursions are permissible within the range of 15 °C to 30 °C (59 °F to 86 °F), in accordance with USP Controlled Room Temperature guidelines. It is critical to avoid freezing both the granules and the reconstituted suspension.

Additionally, the product should be kept out of the reach of children to ensure safety.

Additional Clinical Information

Postmarketing experience has identified several adverse events associated with the use of the medication. Clinicians should be aware of potential blood and lymphatic system disorders, including agranulocytosis and thrombocytopenia. Hepatobiliary disorders such as jaundice, cholestasis, and hepatitis (including hepatocellular injury) have also been reported.

Additionally, immune system disorders may manifest as hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, and angioedema. Neurological effects such as hemiparesis, renal complications like anticoagulant-related nephropathy, and respiratory issues including eosinophilic pneumonia have been noted. Skin reactions can include Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS). Lastly, there have been reports of atraumatic splenic rupture as an injury-related complication.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Xarelto as submitted by Janssen Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)