rivaroxaban
Direct factor Xa inhibitor· Brands: Xarelto, RivaroxPO
Mechanism of action
Rivaroxaban is a direct factor Xa inhibitor. It selectively inhibits factor Xa, preventing the conversion of prothrombin to thrombin, thereby reducing thrombin generation and inhibiting thrombus formation. It does not require antithrombin III for its activity.
Pharmacokinetics
Rivaroxaban is well absorbed orally with high bioavailability (approximately 80-100% for the 10 mg dose, but lower for higher doses due to saturable absorption). Peak plasma concentrations occur 2-4 hours after administration. It is highly bound to plasma proteins (approximately 92-95%). It has a half-life of about 5-9 hours in young subjects, and longer in the elderly. It is metabolized by CYP3A4, CYP2J2, and other enzymes, and eliminated via both renal and biliary pathways. Dose adjustments may be needed in renal impairment.
Indications & dosing
Prophylaxis of venous thromboembolism (VTE) after elective hip or knee replacement surgery
For 35 days after hip surgery, 12 days after knee surgery; give with food.
- adult · PO: 10 mg OD · For 35 days after hip surgery, 12 days after knee surgery; give with food.
Treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE) - initial phase
For first 21 days; give with food.
- adult · PO: 15 mg BD · For first 21 days; give with food.
Treatment of DVT and PE - continued phase
After initial 21 days; give with food.
- adult · PO: 20 mg OD · After initial 21 days; give with food.
Prevention of stroke and systemic embolism in nonvalvular atrial fibrillation
Give with food; reduce to 15 mg if CrCl 15-50 mL/min.
- adult · PO: 20 mg OD · Give with food; reduce to 15 mg if CrCl 15-50 mL/min.
Contraindications & precautions
- Active clinically significant bleeding · Rivaroxaban increases bleeding risk; active bleeding is a contraindication.
- Severe renal impairment (CrCl < 15 mL/min) · Not recommended in patients on dialysis or with CrCl below 15 mL/min.
- Hepatic disease with coagulopathy (Child-Pugh B or C) · Avoid in patients with hepatic impairment that is associated with coagulopathy.
- Hypersensitivity to rivaroxaban or any excipient
- Mechanical heart valve or moderate to severe mitral stenosis · Rivaroxaban is contraindicated in these patients; use with warfarin instead.
- Pregnancy · Rivaroxaban is contraindicated in pregnancy; there are no adequate data.
- Assess renal function before and during treatment; reduce dose to 15 mg once daily if CrCl is 15-50 mL/min, and avoid if CrCl is <15 mL/min.
- Monitor for signs of bleeding and advise patients to report unusual bleeding or bruising.
- Avoid concomitant use of strong CYP3A4 and P-glycoprotein inhibitors (e.g. azole antifungals, ritonavir) or inducers (e.g. rifampicin, phenytoin) as they alter rivaroxaban levels.
- Use caution with neuraxial anaesthesia or spinal puncture due to risk of epidural haematoma; observe for neurological symptoms.
- Caution in patients with hepatic impairment; avoid in Child-Pugh B or C unless benefit outweighs risk.
- Do not stop rivaroxaban abruptly without specialist advice, as it may increase risk of thromboembolism.
Adverse effects
- Bruising
- Major bleeding (including gastrointestinal, intracranial)serious
- Anaemia
- Nausea
- Headache
- Peripheral oedema
- Intracranial haemorrhageserious
- Elevated liver enzymes
Interactions
- clarithromycinmajorAvoid co-prescription of rivaroxaban and clarithromycin. If alternative antibiotics are not suitable, monitor patients closely for signs of bleeding, and consider a temporary reduction in rivaroxaban dose or switching to a less interacting antibiotic such as azithromycin or doxycycline. Assess renal function and reassess anticoagulant requirements during therapy.
- ibuprofenmajorAvoid concurrent use when possible. If combination is necessary, use the lowest effective dose of ibuprofen for the shortest duration. Consider alternative analgesics like paracetamol. Prescribe a proton pump inhibitor for gastroprotection. Monitor patient for signs of bleeding, including haemoglobin, melaena, or unexplained bruising. Advise patient to seek immediate medical attention if bleeding occurs.
- clopidogrelmajorAvoid concomitant use unless the clinical benefit outweighs the bleeding risk. If the combination is necessary, use the lowest effective doses of both agents, monitor the patient closely for signs of bleeding, and consider using a proton pump inhibitor for gastroprotection. Regularly review the ongoing need for dual therapy.
- carbamazepinemajorAvoid co-administration if possible. If combined therapy is necessary, monitor patients closely for signs of thrombosis and consider alternative anticoagulants that are not affected by CYP3A4/P-gp induction. If rivaroxaban is continued, consider dose adjustment and regular assessment of thromboembolic risk. Consult local guidelines and specialist advice.
- diclofenacmajorAvoid concurrent use where possible, especially in patients with high bleeding risk. Consider alternative analgesic or anti-inflammatory therapy, such as paracetamol or a selective cyclo-oxygenase-2 inhibitor, after assessing cardiovascular risk. If co-administration is unavoidable, prescribe the lowest effective dose and shortest duration of diclofenac, and monitor closely for signs of bleeding (e.g., melaena, haematemesis, fall in haemoglobin). Consider gastroprotective therapy with a proton pump inhibitor.
- aspirinmajorUse with caution and only if the expected benefit outweighs the bleeding risk. If combined, prescribe the lowest effective doses, add gastroprotection with a proton pump inhibitor if appropriate, and monitor for signs of bleeding (e.g., haemoglobin, stool colour, mental status). Consider alternative antithrombotic strategies or shorter duration of combination therapy where possible.
Renal & hepatic adjustment
- eGFR 15–50: For non-valvular AF: reduce dose to 15 mg once daily. For VTE treatment: 15 mg twice daily for first 21 days, then 20 mg once daily.
- eGFR 51–300: No dosage adjustment required.
- eGFR 0–14: Avoid use in CrCl <15 mL/min. (avoid)
- Hepatic impairment (mild): No dosage adjustment required (Child-Pugh A).
- Hepatic impairment (moderate): Use with caution (Child-Pugh B); risk of bleeding, consider alternative.
- Hepatic impairment (severe): Contraindicated (Child-Pugh C). (avoid)
Monitoring, pregnancy & toxicity
- Renal function · Baseline and periodically
- Hepatic function · Baseline and periodically in those with hepatic disease
- Signs of bleeding · Throughout treatment
- Haemoglobin · Baseline and if bleeding suspected
- Pregnancy: Contraindicated: teratogenic risk and increased bleeding risk. Use alternative anticoagulant if needed.
- Toxicity: Bleeding complications (e.g., haemorrhage, ecchymosis, GI bleed) · Stop therapy, supportive care, consider activated charcoal if recent ingestion, use prothrombin complex concentrate or factor Xa antidote (andexanet alfa) if severe.
- Toxicity: Overdose may lead to serious bleeding · Andexanet alfa is the specific reversal agent for rivaroxaban. Use activated charcoal within 2-4 hours, monitor for bleeding, and consider four-factor prothrombin complex concentrate if andexanet alfa is unavailable.
Antidotes & reversal
- Andexanet alfa · Specific factor Xa reversal; 4-factor PCC is the usual alternative where andexanet is unavailable.
Clinical notes
Rivaroxaban is indicated for prevention and treatment of venous thromboembolism, prevention of stroke in non-valvular atrial fibrillation, and prevention of venous thromboembolism after orthopaedic surgery. It is taken once or twice daily depending on indication. Caution with renal impairment, hepatic disease, and concurrent use of other anticoagulants or antiplatelets. No routine monitoring of INR required, but bleeding risk must be assessed. It should be taken with food for doses of 15 mg and above to improve absorption.
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BNF; local formulary