Rivaroxaban

Usage

Rivaroxaban is an anticoagulant, specifically a direct factor Xa inhibitor, prescribed for various conditions related to blood clot prevention and treatment. These include:

• Stroke prevention in nonvalvular atrial fibrillation: Reduces the risk of stroke and systemic embolism in patients with this heart rhythm abnormality.
• Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE): Used to treat existing blood clots in the deep veins of the legs (DVT) and lungs (PE).
• Prevention of recurrent DVT and PE: After initial treatment, rivaroxaban helps prevent these clots from forming again.
• Prevention of VTE following hip or knee replacement surgery: Reduces the risk of blood clot formation after these major orthopedic procedures.
• Reduction of risk of major cardiovascular events in patients with coronary artery disease (CAD) or peripheral artery disease (PAD): Used in combination with aspirin to lower the risk of heart attack, stroke, and other cardiovascular complications.
• Treatment of VTE and reduction in the risk of recurrent VTE in pediatric patients: For children who have already received at least 5 days of initial anticoagulation therapy.
• Prophylaxis of VTE in children with congenital heart disease after the Fontan procedure.

Alternate Names

• International Nonproprietary Name (INN): Rivaroxaban
• Brand Name: Xarelto

How It Works

Pharmacodynamics: Rivaroxaban selectively and reversibly inhibits factor Xa, a key enzyme in the coagulation cascade. By blocking factor Xa, rivaroxaban reduces thrombin generation, thereby preventing the formation of fibrin and inhibiting clot formation. It does not require routine coagulation monitoring.

Pharmacokinetics:

• Absorption: Rivaroxaban is rapidly absorbed after oral administration, with peak plasma concentrations occurring within 2 to 4 hours. Bioavailability is high (80-100%) for the 10 mg and 20 mg tablets, while the 2.5 mg tablet has lower bioavailability influenced by food intake.
• Metabolism: Rivaroxaban is metabolized primarily via CYP3A4, CYP2J2, and other pathways, including hydrolysis. About two-thirds of the administered dose is metabolized.
• Elimination: Approximately one-third of the dose is excreted unchanged in the urine and two-thirds as metabolites in the feces and urine. The elimination half-life is 5 to 9 hours in adults (may be longer in the elderly) and 3 to 5.5 hours in pediatric patients.

Mode of Action: Rivaroxaban directly binds to the active site of factor Xa, inhibiting its activity. This prevents the conversion of prothrombin to thrombin, a critical step in clot formation. Rivaroxaban’s action is independent of antithrombin III.

Elimination Pathways: Renal and hepatic excretion, metabolism by CYP enzymes (CYP3A4, CYP2J2).

Dosage

Standard Dosage

Adults:

• Atrial fibrillation: 20 mg once daily with the evening meal (patients with CrCl >50 mL/min); 15 mg once daily (patients with CrCl 15-49 mL/min).
• DVT/PE treatment: 15 mg twice daily with food for 3 weeks, then 20 mg once daily with food.
• Recurrent DVT/PE prevention: 10 mg once daily, with or without food (after at least 6 months of initial treatment).
• Post-operative VTE prophylaxis (hip/knee replacement): 10 mg once daily, starting 6-10 hours after surgery, duration depends on the type of surgery (12 days for knee replacement; 35 days for hip replacement; up to 5 weeks for hip fracture surgery).
• CAD/PAD: 2.5 mg twice daily in combination with aspirin (75-100 mg once daily).

Children (Treatment and Reduction in Risk of Recurrent VTE):

• Dosage is weight-based and administered as an oral suspension or tablets (see source [26] and [28]).
• For detailed weight based dosing please refer to [26] and [28].
• XARELTO 2.5 mg tablets are not recommended for use in pediatric patients.
• Monitor weight regularly to ensure a therapeutic dose, especially for children below 12 kg.

Special Cases:

• Elderly Patients: No dose adjustment is necessary based solely on age, but consider age-related decline in renal and hepatic function. Use with caution in patients ≥75 years old with CAD/PAD receiving rivaroxaban with aspirin.
• Patients with Renal Impairment: Contraindicated if CrCl <15 mL/min or on dialysis. Dose reduction may be required for moderate renal impairment (CrCl 15-49 mL/min) depending on the indication. For specific dosing recommendations based on CrCl for various indications, please consult individual sources.
• Patients with Hepatic Dysfunction: Contraindicated in moderate to severe hepatic impairment (Child-Pugh B and C) or with coagulopathy related to liver disease.
• Patients with Comorbid Conditions: Use with caution in patients with conditions that increase bleeding risk, such as active peptic ulcer disease, recent intracranial hemorrhage, or vascular retinopathy.

Clinical Use Cases Rivaroxaban dosing in clinical settings such as intubation, surgical procedures (other than hip/knee replacement), mechanical ventilation, ICU use, and emergency situations is determined by the specific indication for anticoagulation (e.g., VTE prophylaxis or treatment) and patient-specific factors. Consult specific sources for detailed guidance.

Dosage Adjustments Dose adjustments are based on renal function, potential drug interactions, and bleeding risk. Consult dedicated drug information resources for detailed instructions.

Side Effects

Common Side Effects:

• Bleeding (e.g., bruising, nosebleeds, gum bleeding)
• Anemia
• Dizziness
• Headache
• Back pain
• Gastrointestinal symptoms (nausea, vomiting, diarrhea, abdominal pain)
• Rash
• Peripheral edema

Rare but Serious Side Effects:

• Major bleeding (e.g., gastrointestinal, intracranial)
• Thrombocytopenia
• Allergic reactions (including angioedema)
• Spinal or epidural hematoma (when used with spinal/epidural anesthesia or spinal puncture)

Long-Term Effects: Long-term use can increase the risk of bleeding-related complications.

Adverse Drug Reactions (ADR): Serious bleeding events require urgent medical attention.

Contraindications

• Active pathological bleeding
• Hypersensitivity to rivaroxaban
• CrCl <15 mL/min or on dialysis
• Moderate to severe hepatic impairment (Child-Pugh B and C) or coagulopathy related to liver disease
• Pregnancy (unless the potential benefit outweighs the risk to the fetus). Concurrent use with strong dual inhibitors of CYP3A4 and P-gp (e.g., ketoconazole, itraconazole, posaconazole, ritonavir).

Drug Interactions

Rivaroxaban interacts with numerous medications. Consult a comprehensive drug interaction resource before co-prescribing. Some clinically significant interactions include:

• Anticoagulants and Antiplatelets: Increased bleeding risk.
• CYP3A4 and P-gp Inhibitors: Increased rivaroxaban levels and bleeding risk (e.g., azole antifungals, some HIV protease inhibitors).
• CYP3A4 Inducers: Decreased rivaroxaban levels and efficacy (e.g., rifampin, phenytoin).
• NSAIDs: Increased bleeding risk.

Pregnancy and Breastfeeding

• Pregnancy: Rivaroxaban should be avoided during pregnancy unless the potential benefit justifies the potential risk to the fetus. Data are limited, and potential fetal risks include bleeding.
• Breastfeeding: Rivaroxaban is present in breast milk at low levels. Limited data suggest minimal infant exposure. While breastfeeding may be possible, consult shared decision-making principles and consider individual risk factors.

Drug Profile Summary (See above sections for detailed information)

Popular Combinations

Rivaroxaban is often used in combination with aspirin for CAD/PAD. Combination with other anticoagulants or antiplatelets is generally avoided due to increased bleeding risk.

Precautions (See above sections for detailed information)

FAQs (Frequently Asked Questions)

(See information above to answer the FAQs)