Rivaroxaban

435.88

435.88

1308068-626-2

9NDF7JZ4M3

DTXSID3057723

C77995

White to yellowish powder

B01AF01|B - Blood and blood forming organs

116

2.5

1

1.5±0.1 g/cm3

230 °C

732.6°C at 760 mmHg

396.9±32.9 °C

1.633

Slightly soluble in organic solvents (e.g. acetone, polyethylene glycol 400) and is pratically insoluble in water and aqueous media

Refrigerator

6.66X10-16 mm Hg at 25 deg C (est)

Odorless

Henry's Law constant = 9,46X10-85 atm-cu m/mol at 25 °C (est)

Stable if stored as directed; avoid strong oxidizing agents

P260, P264, P270, P273, P280, P301+P312, P302+P352, P305+P351+P338, P314, P321, P330, P332+P313, P337+P313, P362, P391, P501

H302

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.|SRP: At the time of review, regulatory criteria for small quantity disposal are subject to significant revision, however, household quantities of waste pharmaceuticals may be managed as follows: Mix with wet cat litter or coffee grounds, double bag in plastic, discard in trash.

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including rivaroxaban, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.

|H411 (92.5%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]|P273, P391, and P501|Aggregated GHS information provided by 81 companies from 13 notifications to the ECHA C&L Inventory.

Personal protective equipment as follows: Breathing equipment: NIOSH/MSHA-approved respirator. Protection of hands: chemical-resistant rubber gloves. Eye protection: chemical safety goggles.

Suitable extinguishing agents: water spray, carbon dioxide, dry chemical powder or foam. Protective equipment: wear self-contained breathing apparatus and protective clothing to prevent contact with skin and eyes.

Accidental release measures. After Inhalation: cordon off area of spill; wear self-contained breathing apparatus, protective clothing and heavy rubber gloves. Measures for cleaning/collecting: absorb solutions with finely- powdered liquid-binding material (diatomite, universal binders); decontaminate surfaces and equipment by scrubbing with alcohol; dispose of contaminated material.

Information for safe handling: avoid inhalation and contact with skin, eyes and clothing; material may be an irritant.

Excessive bleeding. Overdosages should be treated using activated charcoal and supportive measures such as mechanical compression and hemodynamic support. If bleeding is not controlled, the following procoagulants can be administered: activated prothrombin complex concentrate, prothrombin complex concentrate and recombinant factor VIIa. There is also a higher chance of post procedural hemorrhage compared to enoxaparin (1.55% vs. 1.39% respectively).

Edoxaban is associated with serum aminotransferase elevations ≥3 times the upper limit of normal in 2% to 5% of treated patients. This rate is similar or lower than rates with warfarin or comparator arms. The elevations are generally transient and not associated with symptoms or jaundice. In premarketing studies, no instances of clinically apparent liver injury were reported, but experience in large numbers of patients treated for extend periods of time is limited.|Chronic therapy with rivaroxaban is associated with moderate ALT elevations (greater than 3 times the upper limit of normal) in 1.5% to 3% of patients, an overall rate which is slightly lower than with low molecular weight heparins and similar to the rates with warfarin. During the large, prelicensure clinical trials of rivaroxaban, several instances of ALT elevations with jaundice occurred, but few details were provided and it was not clear whether the liver injury was clinically apparent. The cases were evidently mild and self-limited, resolving completely once therapy was stopped. Since its licensure and more wide scale use, rivaroxaban has been linked to many instances of acute liver injury with jaundice. The clinical features of these cases varied widely. Most cases had an onset within 1 to 8 weeks of starting rivaroxaban and presented with jaundice, fatigue and a hepatocellular pattern of serum enzyme elevations. In some individuals, a cholestatic or mixed pattern was found. Immunoallergic features and autoimmune markers were atypical but at least one case occurred with skin rash and fever suggestive of DRESS syndrome. One case of acute hepatic necrosis and death attributed to rivaroxaban has been reported, but ischemic hepatitis due to severe heart failure was a more likely cause of the acute liver failure. All other reported cases of rivaroxaban induced liver injury recovered upon stopping rivaroxaban, usually quite promptly, within 2 to 4 weeks.

Patients with renal impairment receiving full dose Xarelto in combination with drugs classified as combined P-gp and weak or moderate CYP3A4 inhibitors (e.g., amiodarone, diltiazem, verapamil, quinidine, ranolazine, dronedarone, felodipine, erythromycin, and azithromycin) may have increases in exposure compared with patients with normal renal function and no inhibitor use, since both pathways of rivaroxaban elimination are affected. Xarelto should be used in patients with CrCl 15 to 50 mL/min who are receiving concomitant combined P-gp and weak or moderate CYP3A4 inhibitors only if the potential benefit justifies the potential risk.|Single doses of enoxaparin and Xarelto given concomitantly resulted in an additive effect on anti-factor Xa activity. Single doses of warfarin and Xarelto resulted in an additive effect on factor Xa inhibition and PT. Concomitant aspirin use has been identified as an independent risk factor for major bleeding in efficacy trials. NSAIDs are known to increase bleeding, and bleeding risk may be increased when NSAIDs are used concomitantly with Xarelto. Coadministration of the platelet aggregation inhibitor clopidogrel and Xarelto resulted in an increase in bleeding time for some subjects. Avoid concurrent use of Xarelto 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.|Results from drug interaction studies and population PK analyses from clinical studies indicate coadministration of Xarelto with a combined P-gp and strong CYP3A4 inducer (e.g., rifampicin, phenytoin) decreased rivaroxaban exposure by up to 50%. Similar decreases in pharmacodynamic effects were also observed. These decreases in exposure to rivaroxaban may decrease efficacy. 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).|When data suggest a change in exposure is unlikely to affect bleeding risk (e.g., clarithromycin, erythromycin), no precautions are necessary during coadministration with drugs that are combined P-gp and CYP3A4 inhibitors. Avoid concomitant administration of Xarelto with combined P-gp and strong CYP3A4 inhibitors.|For more Interactions (Complete) data for Rivaroxaban (10 total), please visit the HSDB record page.

The drug should not be used in patients with a creatinine clearance of less than 15 mL/minute.1 Renal function should be periodically assessed as clinically indicated (i.e., more frequently in situations where renal function may decline) and therapy adjusted accordingly. Rivaroxaban should be discontinued if acute renal failure develops.|Use of rivaroxaban should be avoided in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment or with any hepatic disease associated with coagulopathy; systemic exposure and risk of bleeding may be increased in such patients.

Plasma protein binding is about 92% to 95%

Rivaroxaban is indicated for the prevention of venous thromboembolic events (VTE) in patients who have undergone total hips replacements and total knee replacement surgery; prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation; treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE); to reduce risk of recurrent DVT and/or PE. Rivaroxaban is also indicated, in combination with aspirin, for reducing the risk of major cardiovascular events in patients with chronic coronary artery disease or peripheral artery disease. Due to a lack of safety studies, it is not recommended for use in those under 18 years old. Its use is also not recommended in those with severe renal impairment (<30mL/min).|FDA Label|Xarelto, co-administered with acetylsalicylic acid (ASA) alone or with ASA plus clopidogrel or ticlopidine, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers.Xarelto, co-administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events.Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery.Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults.AdultsPrevention of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack.Paediatric population Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing from 30 kg to 50 kg after at least 5 days of initial parenteral anticoagulation treatment.Paediatric population Treatment of venous thromboembolism (VTE) and prevention of VTE recurrence in children and adolescents aged less than 18 years and weighing more than 50 kg after at least 5 days of initial parenteral anticoagulation treatment.|Prevention of thromboembolic events, Treatment of thromboembolic events|Co administered with acetylsalicylic acid (ASA) alone or with ASA plus ticlopidine, is indicated for the prevention of atherothrombotic events in adult patients after an acute coronary syndrome (ACS) with elevated cardiac biomarkers., , Co administered with acetylsalicylic acid (ASA), is indicated for the prevention of atherothrombotic events in adult patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischaemic events., , Prevention of venous thromboembolism (VTE) in adult patients undergoing elective hip or knee replacement surgery., , Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), and prevention of recurrent DVT and PE in adults., , Prevention of stroke and systemic embolism in adult patients with non‑valvular atrial fibrillation with one or more risk factors, such as congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischaemic attack.,

Edoxaban is an oral, small molecule inhibitor of factor Xa which is used as an anticoagulant to decrease the risk of venous thromboses, systemic embolization and stroke in patients with atrial fibrillation, and as treatment of deep vein thrombosis and pulmonary embolism to prevent thrombotic complications. Edoxaban has been linked to a low rate of serum aminotransferase elevations during therapy, but has not been implicated in cases of clinically apparent acute liver injury.|Rivaroxaban is a recently developed oral anticoagulant and direct factor Xa inhibitor which is used in the prevention of stroke and venous embolism in patients with chronic atrial fibrillation, as well as treatment and prevention of deep venous thromboses and pulmonary embolism. Rivaroxaban has been associated with a low rate of serum enzyme elevations during treatment and with rare instances of clinically apparent liver injury with jaundice.

Anticoagulants|Antithrombotic Agents

Anticoagulant|Xarelto is indicated for the treatment of deep vein thrombosis (DVT). /Included in US product label/|Xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. 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. /Included in US product label/|Xarelto is indicated for the prophylaxis of deep vein thrombosis, which may lead to pulmonary embolism in patients undergoing knee or hip replacement surgery. /Included in US product label/|For more Therapeutic Uses (Complete) data for Rivaroxaban (7 total), please visit the HSDB record page.

/BOXED WARNING/ WARNING: PREMATURE DISCONTINUATION OF XARELTO INCREASES THE RISK OF THROMBOTIC EVENTS. Premature discontinuation of any oral anticoagulant, including Xarelto, increases the risk of thrombotic events. If anticoagulation with Xarelto is discontinued for a reason other than pathological bleeding or completion of a course of therapy, consider coverage with another anticoagulant|/BOXED WARNING/ WARNING: 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. Monitor patients frequently for signs and symptoms of neurological impairment. If neurological compromise is noted, urgent treatment is necessary. Consider the benefits and risks before neuraxial intervention in patients anticoagulated or to be anticoagulated for thromboprophylaxis|Rivaroxaban increases the risk of hemorrhage and can cause serious or fatal bleeding. Bleeding complications were the most common adverse effects of rivaroxaban reported in clinical trials.|Use of rivaroxaban should be avoided in patients with moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment or with any hepatic disease associated with coagulopathy; systemic exposure and risk of bleeding may be increased in such patients.|For more Drug Warnings (Complete) data for Rivaroxaban (13 total), please visit the HSDB record page.

Rivaroxaban is an anticoagulant which binds directly to factor Xa. Thereafter, it effectively blocks the amplification of the coagulation cascade, preventing the formation of thrombus. Rivaroxaban is a unqiue anticoagulant for two reasons. First of all, it is does not involve antithrombin III (ATIII) to exert its anticoagulant effects. Secondly, it is an oral agent whereas the widely used unfractionated heparin and low molecular weight heparins are for parenteral use only. Although the activated partial thromboplastin time (aPTT) and HepTest (a test developed to assay low molecular weight heparins) are prolonged in a dose-dependant manner, neither test is recommended for the assessment of the pharmacodynamic effects of rivaroxaban. Anti-Xa activity and inhibition of anti-Xa activity monitoring is also not recommended despite being influenced by rivaroxaban.

Endogenous factors and drugs that inhibit or block the activity of FACTOR XA. (See all compounds classified as Factor Xa Inhibitors.)

Following oral administration, rivaroxaban is rapidly absorbed and reaches peak plasma concentration in 2-4 hours. Bioavailability of the 10 mg dose is >80%. However, the 15-20 mg dose have a lower bioavailability if taken in the fasted state and consequently should be taken with food.|Approximately two-thirds of rivaroxaban is excreted into urine (via active tubular secretion in which approximately 36% as unchanged drug and 30% as inactive metabolism). The remaining third of the administered dose is excreted via feces in which 7% is in the form of unchanged drug and 21% as inactive metabolites.|The steady state Vd is 50 L|Systemic clearance is approximately 10 L/h, so rivaroxaban is considered a drug with low clearance. Renal clearance is ~3-4 L/h.|Following oral administration, approximately one-third of the absorbed dose is excreted unchanged in the urine, with the remaining two-thirds excreted as inactive metabolites in both the urine and feces. In a Phase 1 study, following the administration of a (14)C-rivaroxaban dose, 66% of the radioactive dose was recovered in urine (36% as unchanged drug) and 28% was recovered in feces (7% as unchanged drug). Unchanged drug is excreted into urine, mainly via active tubular secretion and to a lesser extent via glomerular filtration (approximate 5:1 ratio). Rivaroxaban is a substrate of the efflux transporter proteins P-gp and ABCG2 (also abbreviated Bcrp). Rivaroxaban's affinity for influx transporter proteins is unknown.|Plasma protein binding of rivaroxaban in human plasma is approximately 92% to 95%, with albumin being the main binding component. The steady-state volume of distribution in healthy subjects is approximately 50 L.|Absorption of rivaroxaban is dependent on the site of drug release in the GI tract. A 29% and 56% decrease in AUC and Cmax compared to tablet was reported when rivaroxaban granulate is released in the proximal small intestine. Exposure is further reduced when drug is released in the distal small intestine, or ascending colon. Avoid administration of rivaroxaban distal to the stomach which can result in reduced absorption and related drug exposure.|The absolute bioavailability of rivaroxaban is dose-dependent. For the 10 mg dose, it is estimated to be 80% to 100% and is not affected by food. Xarelto 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). Xarelto 15 mg and 20 mg tablets should be taken with food.|For more Absorption, Distribution and Excretion (Complete) data for Rivaroxaban (8 total), please visit the HSDB record page.

Approximately two-thirds of the dose is metabolized. It is metabolized by CYP3A4, CYP3A5, CYP2J2 and CYP-independant mechanisms|Rivaroxaban undergoes oxidative degradation by cytochrome P-450 (CYP) isoenzymes 3A4/5 and 2J2 and hydrolysis; metabolites are subsequently eliminated through renal and fecal/biliary routes. No major circulating metabolites have been identified in plasma.

The terminal half life is 5-9 hours in adults and 11-13 hours in the elderly.|The terminal elimination half-life is 11 to 13 hours in the elderly.|The terminal elimination half-life of rivaroxaban is 5 to 9 hours in healthy subjects aged 20 to 45 years.

Rivaroxaban competitively inhibits free and clot bound factor Xa. Factor Xa is needed to activate prothrombin (factor II) to thrombin (factor IIa). Thrombin is a serine protease that is required to activate fibrinogen to fibrin, which is the loose meshwork that completes the clotting process. Since one molecule of factor Xa can generate more than 1000 molecules of thrombin, selective inhibitors of factor Xa are profoundly useful in terminating the amplification of thrombin generation. The action of rivaroxaban is irreversible.|Rivaroxaban, an oral, direct activated factor X (Xa) inhibitor, is an anticoagulant. Factor Xa plays a central role in the blood coagulation cascade by serving as the convergence point for the intrinsic and extrinsic pathways; inhibition of coagulation factor Xa by rivaroxaban prevents conversion of prothrombin to thrombin and subsequent thrombus formation. Rivaroxaban inhibits both free and prothrombinase-bound factor Xa. Unlike fondaparinux, heparin, and the low molecular weight heparins, rivaroxaban binds directly to the active site of factor Xa without the need for a cofactor (e.g., antithrombin III). Rivaroxaban inhibits factor Xa with more than 100,000-fold greater selectivity than other biologically important serine proteases (e.g., thrombin, trypsin, plasmin, factor VIIa, factor IXa, urokinase, activated protein C).|Xarelto is an orally bioavailable factor Xa inhibitor that selectively blocks the active site of factor Xa and does not require a cofactor (such as Anti-thrombin III) for activity. Activation of factor X to factor Xa (FXa) via the intrinsic and extrinsic pathways plays a central role in the cascade of blood coagulation.

EXPERIMENTAL: Rivaroxaban is an oral, direct factor Xa inhibitor for the management of thromboembolic disorders. Despite its short half-life, the ability to reverse rivaroxaban anticoagulation could be beneficial in life-threatening emergencies. The potential of prothrombin complex concentrate (PCC; Beriplex), activated PCC (aPCC; FEIBA) or recombinant activated factor VII (rFVIIa; NovoSeven) to reverse rivaroxaban in rats and baboons was investigated. Anaesthetised rats pre-treated with intravenous rivaroxaban (2 mg/kg) received intravenous rFVIIa (100/400 ug/kg), PCC (25/50 U/kg) or aPCC (50/100 U/kg) after initiation of bleeding. Clotting times and bleeding times (BTs) were recorded. Rivaroxaban was administered as an intravenous 0.6 mg/kg bolus followed by continuous 0.6 mg/kg/hour infusion in baboons. Animals received intravenous aPCC 50 U/kg (2 U/kg/minute) or rFVIIa 210 ug/kg. BT and clotting parameters were measured. In rats pretreated with high-dose rivaroxaban, PCC 50 U/kg, aPCC 100 U/kg and rFVIIa 400 ug/kg significantly reduced BT vs rivaroxaban alone (5.4 + or- 1.4-fold to 1.5 + or- 0.4-fold [p<0.05]; 3.0+ or- 0.4-fold to 1.4 + or- 0.1-fold [p<0.001]; and 3.5 + or- 0.7-fold to 1.7 + or- 0.2-fold [p<0.01] vs baseline, respectively). In baboons pre-infused with rivaroxaban and then given aPCC, BT increased by 2.0 + or- 0.2-fold and aPCC returned BT to baseline for the duration of its infusion. rFVIIa reduced BT from 2.5 + or- 0.3-fold over baseline to 1.7 + or- 0.3-fold over baseline. Prolongation of prothrombin time was reduced by PCC, aPCC and rFVIIa in both species. Rivaroxaban reduced thrombin-antithrombin levels; application of PCC and aPCC, but not rFVIIa, increased these levels. In conclusion, PCC, aPCC or rFVIIa have the potential to reverse the anticoagulant and anti-haemostatic effects of rivaroxaban.|Overdose of Xarelto may lead to hemorrhage. Discontinue Xarelto and initiate appropriate therapy if bleeding complications associated with overdosage occur. A specific antidote for rivaroxaban is not available. 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 Xarelto overdose may be considered. Due to the high plasma protein binding, rivaroxaban is not expected to be dialyzable.|/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/CASE REPORTS/ A 61-year-old female patient who developed a spontaneous spinal epidural hematoma (SSEH) after being treated by rivaroxaban, a new agent for the prevention of venous thromboembolic events in orthopedic surgery /is reported/. Although the pathogenesis of SSEH is unclear, anticoagulant therapy is a known risk factor. The patient sustained a sudden onset of severe back pain in the thoracic spine, followed by paraplegia below T8, 2 days after proximal tibial osteotomy and rivaroxaban therapy. Magnetic resonance imaging (MRI) of the whole spine demonstrated a ventral SSEH from C2 to T8. Whilst preparing for the emergency evacuation of the SSEH, the neurological symptoms recovered spontaneously 4 hr after onset without surgery. After monitored bed rest for 48 hr the MRI was repeated and the SSEH was no longer present. This rare condition of spinal cord compression and unusually rapid spontaneous recovery has not previously been reported following rivaroxaban therapy.|/CASE REPORTS/ Managing patients with new oral anticoagulants in perioperative period is not yet well protocolized. ... A clinical case of a critical hematuria after prostate biopsies to a patient treated with RIivaroxaban /is reported/. Monitoring and treatment of the hematuria have been difficult due to the lack of biological control and antidote for this treatment.|/ALTERNATIVE and IN VITRO TESTS/ Blood from patients with known coronary artery disease who were treated with aspirin but no other antithrombotic agent was spiked in vitro with rivaroxaban alone or in combination with a direct acting P2Y12 antagonist (cangrelor). To limit cofounding effects of anticoagulants and to enable interaction between coagulation factors, blood was anticoagulated only with a specific inhibitor of Factor XIIa, corn trypsin inhibitor. Polymerization of fibrin was prevented with the peptide GPRP. Activation of platelets was determined with the use of flow cytometry in response to lipidated tissue factor, thrombin, the collagen mimetic convulxin, and adenosine diphosphate (ADP). Rivaroxaban inhibited the activation of platelets induced by tissue factor and to a lesser extent activation induced by thrombin, effects that were accentuated when combined with cangrelor. Rivaroxaban did not attenuate convulxin-induced activation of platelets; however, a limited but consistent attenuation of ADP-induced platelet activation was seen with blood anticoagulated with rivaroxaban. Effects of rivaroxaban on ADP-induced platelet activation were not mediated by thrombin, tissue factor, or platelet-leukocyte aggregation. In conclusion, rivaroxaban attenuated in vitro the activation of platelets mediated by thrombin. In light of the pivotal role of thrombin in platelet activation after rupture of an atherosclerotic plaque, rivaroxaban should attenuate platelet activation in vivo, an effect that is accentuated by combination with a P2Y12 antagonist.|/ALTERNATIVE and IN VITRO TESTS/ ... This study investigated the direct effects of rivaroxaban on bone biology using an in vitro cell culture model from the human female osteoblastic cell line SaOS2. Cells at subconfluence were treated for 24 hr with different concentrations of rivaroxaban and analyzed for DNA synthesis and creatine kinase- and alkaline phosphatase-specific activities, and were treated 21 days for analyzing mineralization. Rivaroxaban (0.01-50 ug/mL) dose-dependently inhibited up to 60% DNA synthesis of the cells. Creatine kinase-specific activity was also inhibited dose-dependently to a similar extent by the same concentrations. Alkaline phosphatase-specific activity was dose-dependently inhibited but only up to 30%. Cell mineralization was unaffected by 10 ug/mL rivaroxaban. This model demonstrated a significant rivaroxaban-induced reduction in osteoblastic cell growth and energy metabolism, and slight inhibition of the osteoblastic marker, alkaline phosphatase, while osteoblastic mineralization was unaffected. These findings might indicate that rivaroxaban inhibits the first stage of bone formation but does not affect later stages (i.e., bone mineralization).

5-chloro-N-(((5S)-2-oxo-3-(4-(3-oxomorpholin-4-yl)phenyl)-1,3-oxazolidin-5-yl)methyl)thiophene-2-carboxamide

Table: Rivaroxaban Preparations [Table#8124]

HPLC-MS/MS determination in plasma.

Human drugs -> Xarelto -> EMA Drug Category|Antithrombotic agents -> Human pharmacotherapeutic group|Human Drugs -> EU pediatric investigation plans|Human drugs -> Rivaroxaban Accord -> EMA Drug Category|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients