AF is frequently treated with pharmacological therapies that mainly consist of direct oral anticoagulants. Within this drug group, rivaroxaban (a factor Xa inhibitor) has emerged demonstrating efficacy in stroke prevention and providing a further benefit of convenient dosing regimens.(S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl (Rivaroxaban） is used to treat or prevent blood clots. Blood clots can occur in the legs or the lungs. Rivaroxaban is sometimes used to lower your risk of a blood clot coming back after you have received treatment for blood clots for at least 6 months in adults, and at least 5 days in children from birth to less than 18 years of age.Rivaroxaban is also given together with aspirin to lower the risk of stroke, heart attack, or other serious heart and blood circulation problems in adults with coronary artery disease (clogged arteries) or peripheral artery disease, including adults who recently had a procedure to improve blood flow to the legs. (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl can also be used to prevent blood clots in adults that are not able to move as normal during and after a hospital stay or after a hip or knee replacement surgery. Rivaroxaban can cause you to bleed more easily. Call your doctor at once if you have signs of bleeding such as: pain, swelling, new drainage, or excessive bleeding from a wound.

Clinical and Research Information on Drug-Induced Liver Injury

(S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl is an 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. Rivaroxaban was approved for use in the United States in 2011, the first oral factor Xa inhibitor to become available. Current indications are for prevention of stroke and embolism in patients with chronic atrial fibrillation not related to valvular heart disease, as well as prevention and treatment of deep vein thrombosis and pulmonary embolism in patients at high risk. Long term therapy in low doses given twice daily in combination with aspirin has been shown to decrease major cardiovascular events and death in patients with coronary or peripheral artery disease.  Side effects not directly attributable to the anticoagulant activity of (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl are not common, but can include nausea, abdominal discomfort, back pain, anorexia, fever, and skin rash. Severe adverse events include major bleeding episodes, epidural or spinal hematoma, and increase in risk of thrombotic events with premature discontinuation.[1]

The cause of liver injury during (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl therapy is unknown, but is likely to be idiosyncratic and perhaps immunologic. Rivaroxaban is metabolized in the liver largely by CYP 3A4 and is susceptible to drug-drug interactions; inhibitors of CYP 3A4 (such as clarithromycin and itraconazole) can lead to increased levels, while inducers of CYP 3A4 (such as rifampin and phenytoin) can cause decreased and potential subtherapeutic drug levels. During the large, prelicensure clinical trials of (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl, 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. Liver injury attributed to (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl varies from mild serum ALT elevations to liver injury with jaundice, but is usually mild to moderate in severity and self-limited, resolving within a few weeks of stopping. Convincing examples of acute liver failure, chronic hepatitis or vanishing bile duct syndrome due to rivaroxaban have not been reported in the published literature.

Rivaroxaban in Healthy Human Subjects

(S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl  is a direct Factor Xa inhibitor and has been approved for the prevention of venous thromboembolism in adults undergoing hip or knee replacement surgery, the prevention of stroke and systemic embolism in adults with non-valvular atrial fibrillation and for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE), as well as the prevention of recurrent DVT and PE in adult patients. In human plasma, rivaroxaban has been shown to inhibit thrombin production and, thus, the amplification processes of coagulation, through the inhibition of endogenous Factor Xa (IC50 of 21 nM). Therapeutically relevant concentrations of (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl (80-100 nM) are sufficient to cause almost complete inhibition of thrombin generation.[2]

Overall, in healthy subjects, (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl  was shown to exhibit predictable and dose-proportional pharmacokinetics in the fed state without dose accumulation beyond a steady state. Demographic variations had little influence on rivaroxaban’s pharmacokinetics, except for age, but its effect was found to be insignificant after adjusting for renal function. To summarise, the high oral bioavailability, the low-to-moderate potential for peripheral tissue penetration, combined with the absence of major or active metabolites in human plasma and its relatively short half-life, highlight rivaroxaban’s favorable pharmacokinetics and justify its central role in current anticoagulation management across several thromboembolic conditions.

Rivaroxaban for Stroke Prevention

Atrial fibrillation is frequently treated with pharmacological therapies that mainly consist of direct oral anticoagulants. Within this drug group, (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl (a factor Xa inhibitor) has emerged demonstrating efficacy in stroke prevention and providing a further benefit of convenient dosing regimens. Recent trials demonstrate the comparative risks and benefits of (S)-4-(4-(5-(Aminomethyl)-2-oxooxazolidin-3-yl)phenyl)morpholin-3-one.HCl in comparison with conventional forms of pharmacological therapies. The clinical implications drawn from this analysis advocate for a thoughtful and patient-centered approach to anticoagulation therapy in AF. There is little impact of difference in the dosing of rivaroxaban with slightly reduced risk of stroke risk with standard dosing but with raised bleeding events.[3]

References

[1]LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Rivaroxaban.

[2]Bratsos S. Pharmacokinetic Properties of Rivaroxaban in Healthy Human Subjects. Cureus. 2019 Aug 25;11(8):e5484. doi: 10.7759/cureus.5484. PMID: 31489274; PMCID: PMC6713240.

[3]Virk GS, Javed S, Chaudhry R, Moazam MM, Mahmood A, Mahmood F, Zaheer M, Khan SM, Rajasekaran V. Assessing the Safety and Efficacy of Rivaroxaban for Stroke Prevention in Patients With Atrial Fibrillation: A Systemic Review and Meta-Analysis. Cureus. 2024 Feb 15;16(2):e54252. doi: 10.7759/cureus.54252. PMID: 38496142; PMCID: PMC10944328.