Rixoban

Approved Indications:

• Prevention of Stroke and Systemic Embolism in Nonvalvular Atrial Fibrillation: In adults with nonvalvular atrial fibrillation and one or more risk factors (e.g., previous stroke, hypertension, diabetes, heart failure).
• Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE): Initial and continued treatment to prevent recurrence.
• Reduction in the Risk of Recurrence of DVT and/or PE: After completing initial 6 months of treatment.
• Prophylaxis of DVT Following Hip or Knee Replacement Surgery: To reduce risk of postoperative venous thromboembolism.
• Prevention of Atherothrombotic Events in Patients with Coronary Artery Disease (CAD) or Peripheral Artery Disease (PAD): In combination with low-dose aspirin.
• Thromboprophylaxis in Hospitalized Acutely Ill Medical Patients: Who are at risk of thromboembolism and not at high bleeding risk (in some regions).

Off-label/Clinically Accepted Uses:

• Prevention of venous thromboembolism in cancer-associated thrombosis (as alternative to LMWH).
• Use in antiphospholipid syndrome (with caution; not universally recommended).

Route: Oral administration.
Form: Film-coated tablets (10 mg, 15 mg, 20 mg).
Administration: With food for doses ≥15 mg; 10 mg may be taken with or without food.

Adults:

• Nonvalvular Atrial Fibrillation: 20 mg once daily with evening meal; reduce to 15 mg once daily if CrCl 15–50 mL/min.
• DVT/PE Treatment: 15 mg twice daily for 21 days, then 20 mg once daily thereafter.
• DVT/PE Secondary Prevention: 10 mg once daily (if long-term therapy needed, especially beyond 6 months).
• Hip/Knee Replacement Prophylaxis: 10 mg once daily. Duration:
• Hip: 35 days
• Knee: 12 days
• CAD/PAD (with aspirin): 2.5 mg twice daily + aspirin 75–100 mg once daily.

Pediatric:

• Approved in some regions for pediatric VTE treatment and prophylaxis; dose based on body weight and age.

Renal Impairment:

• Avoid use in CrCl <15 mL/min.
• Use with caution in moderate impairment; dose adjustment required.

Hepatic Impairment:

• Contraindicated in moderate to severe hepatic disease associated with coagulopathy.

Rivaroxaban is a highly selective, direct Factor Xa inhibitor. It inhibits free Factor Xa, as well as prothrombinase-bound and clot-associated Factor Xa. By inhibiting this key enzyme in the coagulation cascade, it interrupts the conversion of prothrombin to thrombin, thereby reducing thrombin generation, thrombus development, and clot formation. Its action is independent of antithrombin III, unlike traditional anticoagulants such as heparin. This targeted inhibition leads to predictable anticoagulation with fixed dosing and without the need for routine monitoring.

• Absorption: Rapid, with peak plasma concentrations in 2–4 hours. Bioavailability ~80–100% for 10 mg dose; reduced if ≥15 mg taken without food.
• Distribution: Volume of distribution ~50 L; 92–95% protein-bound (mainly albumin).
• Metabolism: Primarily metabolized by CYP3A4, CYP2J2, and CYP-independent mechanisms. Involves hydrolysis and oxidation.
• Excretion: One-third excreted unchanged in urine; the remainder eliminated as metabolites via urine and feces.
• Half-life: 5–9 hours (young adults), 11–13 hours (elderly).
• Steady-state: Achieved within 2–3 days.

• Pregnancy: Not assigned an FDA category under new labeling rules. Use is not recommended during pregnancy due to potential risk of bleeding and lack of data on fetal safety.
• Lactation: Excreted in breast milk (animal studies); not recommended in breastfeeding women. Alternative anticoagulants preferred.
• Caution: Women of childbearing potential should use effective contraception during treatment.

• Primary Class: Oral Anticoagulant
• Subclass: Direct Factor Xa Inhibitor (DOAC/NOAC – Non-Vitamin K Oral Anticoagulant)

• Known hypersensitivity to rivaroxaban or any component of the formulation
• Active major bleeding
• Severe hepatic impairment with associated coagulopathy
• Creatinine clearance <15 mL/min
• Pregnancy and lactation (relative contraindication)
• Concomitant use with other anticoagulants unless switching therapy or during catheter procedures

• Bleeding Risk: May cause serious or fatal bleeding. Monitor for signs of bleeding, especially in elderly or those with renal/hepatic impairment.
• Spinal/Epidural Hematoma: Risk increased in patients receiving neuraxial anesthesia or spinal puncture; may lead to long-term or permanent paralysis.
• Renal Function Monitoring: Required before and during treatment.
• Hepatic Impairment: Increased exposure; avoid use in moderate/severe dysfunction.
• Thrombocytopenia/Coagulation Disorders: Use with caution.
• Discontinuation Risk: Abrupt discontinuation increases risk of thrombotic events.

Common:

• Gastrointestinal: Nausea, dyspepsia, constipation
• Bleeding: Epistaxis, gingival bleeding, menorrhagia, hematuria
• General: Fatigue, dizziness, headache

Serious:

• Intracranial hemorrhage
• Gastrointestinal hemorrhage
• Hematuria, retroperitoneal bleeding
• Hepatic dysfunction (rarely)
• Anaphylaxis (very rare)

Onset: Bleeding complications may occur early in therapy, especially in high-risk patients.

• Major Enzyme Pathways: CYP3A4 and P-gp
• Strong CYP3A4 and P-gp Inhibitors: (e.g., ketoconazole, ritonavir) ↑ bleeding risk — avoid.
• Strong CYP3A4 and P-gp Inducers: (e.g., rifampicin, phenytoin) ↓ efficacy — avoid.
• NSAIDs/Antiplatelets: Additive bleeding risk.
• Other Anticoagulants: Concurrent use not advised unless transitioning.
• St. John’s Wort: Induces CYP3A4 — avoid due to reduced anticoagulant effect.
• Alcohol: Increased bleeding risk with excessive intake.

• FDA/EMA Updates: New indication approved for expanded use in CAD/PAD with low-dose aspirin.
• Guidelines: ACC, ESC, and CHEST continue to recommend rivaroxaban as a first-line DOAC for stroke prevention in AF and for DVT/PE management.
• COVID-19 Era: DOACs including rivaroxaban explored for thromboprophylaxis in post-hospitalized COVID patients (clinical judgment advised).

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Humidity: Protect from moisture. Keep tablets in original packaging until use.
• Light Protection: Not required.
• Handling: No special handling precautions required. Do not break or crush tablets unless necessary for specific formulations.
• Shelf-life: As per manufacturer’s label (typically 3 years).