Schedule H

Oral

• Tablets: 2.5 mg, 10 mg, 15 mg, 20 mg

Note: Oral suspension/granules NOT AVAILABLE in India

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Prevention of Stroke and Systemic Embolism in Non-Valvular Atrial Fibrillation (NVAF)

Adults with CrCl ≥50 mL/min:

Parameter Recommendation

Starting dose 20 mg once daily with food (evening meal preferred)

Titration Not applicable

Usual maintenance dose 20 mg once daily

Maximum dose 20 mg/day

Adults with CrCl 15–49 mL/min:

Parameter Recommendation

Starting dose 15 mg once daily with food

Titration Not applicable

Usual maintenance dose 15 mg once daily

Maximum dose 15 mg/day

Clinical Notes:

• Avoid if CrCl <15 mL/min

• Must be taken with food to ensure adequate bioavailability (15 mg and 20 mg doses)

• Contraindicated in valvular AF (mechanical prosthetic valves, moderate-to-severe mitral stenosis)

1. Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE)

Adults — Acute Treatment Phase (Days 1–21):

Parameter Recommendation

Starting dose 15 mg twice daily with food

Titration Not applicable during loading phase

Duration 21 days

Maximum dose 30 mg/day (during loading phase)

Adults — Maintenance Phase (Day 22 onwards):

Parameter Recommendation

Starting dose 20 mg once daily with food (from Day 22)

Titration Not applicable

Usual maintenance dose 20 mg once daily

Maximum dose 20 mg/day

Clinical Notes:

• Minimum treatment duration: 3 months

• Provoked VTE (reversible risk factor): 3 months usually sufficient

• Unprovoked or recurrent VTE: consider extended therapy beyond 3 months

• Assess bleeding risk periodically during long-term therapy

1. Prevention of Recurrent DVT and PE (Extended Secondary Prevention)

Adults — After Completion of Initial Treatment:

Parameter Recommendation

Starting dose 10 mg once daily (with or without food)

Titration Not applicable

Usual maintenance dose 10 mg once daily

Maximum dose 20 mg once daily (may be used if high recurrence risk)

Clinical Notes:

• Initiate after at least 6 months of standard anticoagulation

• 20 mg dose may be preferred if VTE recurred during anticoagulation or very high risk

• Periodically reassess need for continued therapy versus bleeding risk

1. Prophylaxis of VTE after Elective Hip or Knee Replacement Surgery

Adults:

Parameter Recommendation

Starting dose 10 mg once daily

Timing of first dose 6–10 hours post-surgery, after haemostasis established

Titration Not applicable

Usual maintenance dose 10 mg once daily

Maximum dose 10 mg/day

Duration:

• Knee replacement: 14 days

• Hip replacement: 35 days

Clinical Notes:

• May be taken with or without food (10 mg dose)

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Regulatory Status: NOT approved for routine paediatric use in India. Paediatric oral suspension formulation NOT AVAILABLE in India.

Age Restriction: Not recommended below 18 years except under specialist haematology/cardiology supervision.

Secondary Indications – Paediatric (Off-label)

Treatment of Acute VTE in Children — OFF-LABEL

Use only when LMWH or warfarin unsuitable and under specialist supervision

Minimum Age/Weight: ≥6 months of age, ≥2.6 kg body weight

Body Weight Approximate Daily Dose Administration

2.6–<12 kg Weight-band based — requires specialist calculation Crushed tablets in water/apple puree (not ideal; suspension not available)

12–<30 kg 10–15 mg/day in 1–2 divided doses With food

≥30 kg 15–20 mg once daily With food

Clinical Notes:

• Dosing extrapolated from international paediatric trials (EINSTEIN-Jr)

• Lack of appropriate paediatric formulation in India limits practical use

• LMWH remains preferred anticoagulant in paediatric VTE in India

• Requires close specialist supervision (paediatric haematology/cardiology)

Safety Monitoring:

• CBC, renal function, liver function at baseline and periodically

• Clinical monitoring for bleeding

• Anti-Xa levels generally not required but may be considered in complex cases

Indication CrCl ≥50 mL/min CrCl 30–49 mL/min CrCl 15–29 mL/min CrCl <15 mL/min

NVAF (stroke prevention) 20 mg OD 15 mg OD 15 mg OD (use with caution) Avoid

VTE treatment (acute) 15 mg BD → 20 mg OD 15 mg BD → 20 mg OD Use with caution; limited data Avoid

VTE prevention (orthopaedic) 10 mg OD 10 mg OD 10 mg OD (use with caution) Avoid

Extended VTE prevention 10 mg OD 10 mg OD Use with caution Avoid

CAD/PAD + Aspirin 2.5 mg BD 2.5 mg BD Use with caution Avoid

Dialysis:

• Haemodialysis: Not recommended — rivaroxaban is highly protein-bound and not effectively dialysed

• Peritoneal dialysis: Avoid — insufficient data

Monitoring: Reassess renal function every 6 months in stable patients; more frequently if acute illness, dehydration, or nephrotoxic drugs used.

Hepatic disease with coagulopathy Contraindicated regardless of Child-Pugh class

• Active clinically significant bleeding (including GI, intracranial, or any site)

• Hepatic disease associated with coagulopathy and clinically relevant bleeding risk

• Severe renal impairment (CrCl <15 mL/min)

• Known hypersensitivity to rivaroxaban or excipients

• Pregnancy (particularly second and third trimesters)

• Lesions at high risk of clinically significant bleeding (e.g., active peptic ulcer, recent brain/spinal surgery, intracranial neoplasm)

• Concomitant treatment with any other anticoagulant (except during transition periods)

• Concomitant use with strong CYP3A4 and P-glycoprotein inhibitors (e.g., ketoconazole, itraconazole, ritonavir, lopinavir)

• Mechanical prosthetic heart valves

• Moderate-to-severe mitral stenosis of rheumatic origin

• Moderate renal impairment (CrCl 15–49 mL/min) — dose reduction may be needed; monitor closely

• Elderly patients (≥75 years) — increased bleeding risk

• Low body weight (<50 kg) — potential for increased drug exposure

• Concomitant use of antiplatelet agents (aspirin, clopidogrel, prasugrel, ticagrelor) — additive bleeding risk

• Chronic NSAID use — increased GI bleeding risk

• Recent major surgery or trauma

• History of GI bleeding or peptic ulcer disease

• Uncontrolled severe hypertension

• Bronchiectasis or history of pulmonary bleeding

• Neuraxial anaesthesia or spinal puncture — risk of epidural/spinal haematoma

• Delay rivaroxaban for at least 18 hours after catheter removal

• Remove catheter at least 18 hours after last rivaroxaban dose

• Moderate hepatic impairment (Child-Pugh B) — increased exposure

• Patients with antiphospholipid syndrome (especially triple-positive) — warfarin preferred

Parameter Details

Risk category Contraindicated — crosses placenta; potential for fetal bleeding, teratogenicity (animal data)

Preferred alternatives Low Molecular Weight Heparin (LMWH) — enoxaparin is anticoagulant of choice in pregnancy in India

When may be used Only in exceptional circumstances if LMWH absolutely contraindicated and no alternative exists; requires specialist decision

Monitoring If inadvertent exposure: fetal ultrasound for anomalies, monitor for bleeding; plan delivery with haematology input

Parameter Details

Compatibility Not recommended during breastfeeding

Drug levels in milk Excreted in breast milk; infant exposure uncertain

Preferred alternatives LMWH (enoxaparin) — not excreted in breast milk; warfarin — compatible with breastfeeding

Infant monitoring If exposure occurs: monitor for bleeding signs, bruising, feeding difficulties

Parameter Recommendation

Starting dose Same as younger adults, but assess renal function before prescribing

Titration Not applicable — fixed dosing regimen

Special risks Increased bleeding risk (particularly GI and intracranial); higher prevalence of renal impairment; falls risk; polypharmacy with interacting drugs

Monitoring Renal function at baseline and every 6 months; more frequently if acute illness; regular clinical assessment for bleeding

Drug/Class Mechanism/Effect Recommendation

Strong CYP3A4 + P-gp inhibitors (ketoconazole, itraconazole, voriconazole, posaconazole, ritonavir, lopinavir) Marked increase in rivaroxaban exposure → high bleeding risk Contraindicated — avoid concomitant use

Strong CYP3A4 inducers (rifampicin, rifabutin, carbamazepine, phenytoin, phenobarbital, St. John's Wort) Significant reduction in rivaroxaban levels → loss of efficacy Avoid — therapeutic failure likely

Other anticoagulants (warfarin, LMWH, UFH, fondaparinux, other DOACs) Additive anticoagulant effect → major bleeding risk Avoid — exception: brief overlap during transition (specialist supervision)

Thrombolytics (alteplase, tenecteplase, streptokinase) Markedly increased bleeding risk Avoid concomitant use; hold rivaroxaban during thrombolysis

Dual antiplatelet therapy (DAPT — aspirin + P2Y12 inhibitor) Significantly increased bleeding risk Use with extreme caution; triple therapy duration should be minimised; specialist decision

Drug/Class Effect Recommendation

Single antiplatelet (aspirin, clopidogrel) Increased bleeding risk Use only when indicated (CAD/PAD); monitor for bleeding

NSAIDs (diclofenac, ibuprofen, naproxen) Increased GI bleeding risk Avoid chronic use; if short-term use required, consider gastroprotection

Moderate CYP3A4 inhibitors (erythromycin, clarithromycin, fluconazole, diltiazem, verapamil) Modest increase in rivaroxaban levels Use with caution; monitor for bleeding

Dronedarone Increases rivaroxaban exposure Avoid if possible; if used, monitor closely

Amiodarone Mild increase in rivaroxaban levels Generally acceptable; monitor for bleeding

SSRIs/SNRIs (fluoxetine, sertraline, venlafaxine) Increased bleeding tendency (platelet effect) Monitor for bleeding; counsel patient

Proton pump inhibitors No significant interaction Can be used together; useful for gastroprotection

• Bleeding — minor (epistaxis, gingival bleeding, bruising, menorrhagia)

• Anaemia (may be occult GI blood loss)

• Nausea, dyspepsia

• Diarrhoea or constipation

• Dizziness

• Headache

• Peripheral oedema

• Mild transaminase elevation

• Fatigue

Adverse Effect Clinical Action

Major bleeding (GI haemorrhage, intracranial haemorrhage, retroperitoneal bleeding) Immediate discontinuation; supportive care; consider reversal agent (andexanet alfa if available) or prothrombin complex concentrate; hospitalisation

Spinal/Epidural haematoma (with neuraxial procedures) Emergency — can cause permanent paralysis; urgent neurosurgical consultation

Severe hypersensitivity/Anaphylaxis Discontinue immediately; emergency management

Hepatotoxicity (rare) Discontinue if significant transaminase elevation (>3× ULN with symptoms)

Thrombocytopenia (rare) Monitor; may need to discontinue

Compartment syndrome (in setting of bleeding) Surgical emergency

Reversal in Major Bleeding:

• Andexanet alfa — specific reversal agent (limited availability in India)

• Prothrombin Complex Concentrate (PCC) — 4-factor PCC 25–50 units/kg

• Tranexamic acid — adjunctive

• Activated charcoal — if ingestion within 2 hours

• No role for FFP, vitamin K, or protamine

Baseline:

• Complete blood count (haemoglobin, platelet count)

• Renal function (serum creatinine, calculated CrCl)

• Liver function tests (transaminases, bilirubin)

• Coagulation screen (PT/INR) — for baseline documentation only, not for monitoring

• Bleeding risk assessment (HAS-BLED score for AF patients)

After Initiation / Dose Change:

• Clinical assessment for bleeding at 1 month

• Renal function at 1–3 months (especially in elderly, CKD, acute illness)

• Haemoglobin if bleeding suspected

Long-term Monitoring:

• Renal function: Every 6–12 months in stable patients; more frequently if CrCl <60 or at-risk (elderly, diabetes, heart failure, dehydration)

• Haemoglobin and haematocrit: Annually or if bleeding symptoms

• Liver function: Annually or if symptoms suggestive of hepatotoxicity

• Clinical bleeding assessment at every visit

• Reassess indication and bleeding risk annually

Note: Routine coagulation monitoring (PT/INR, aPTT) not required and not reliable for assessing rivaroxaban effect. Anti-Xa chromogenic assay (rivaroxaban-calibrated) may be used in special situations (overdose, emergency surgery, extremes of body weight).

Originator:

• Xarelto (Bayer/Zydus)

Generic/Licensed Brands:

• Rivasmart (Cipla)

• Xaban (Dr. Reddy's)

• Rivaxo (Sun Pharma)

• Rivaxa (Torrent)

• Rivonex (Mankind)

• Xeralto (Macleods)

• Rixova (Intas)

• Rivaz (Alkem)

Fixed-Dose Combinations:

• Not currently under NPPA price control

• Not included in NLEM 2022

• Significant price variation between originator and generic brands

• Generic options substantially more affordable

1. Food is essential for higher doses — 15 mg and 20 mg doses must be taken with food to ensure adequate bioavailability (~66% fasting vs ~100% with food); 2.5 mg and 10 mg can be taken with or without food

1. Not for valvular AF — rivaroxaban is contraindicated in mechanical prosthetic valves and moderate-to-severe rheumatic mitral stenosis; use warfarin for these patients

1. Renal function determines dose in AF — always calculate CrCl (Cockcroft-Gault); if CrCl 15–49 mL/min, use 15 mg OD; avoid if <15 mL/min

1. No bridging required — unlike warfarin, rivaroxaban has rapid onset (2–4 hours) and offset; avoid overlapping with LMWH except in specific transition scenarios

1. Beware triple therapy — combination with DAPT (aspirin + P2Y12 inhibitor) markedly increases bleeding; minimise duration and consider 15 mg OD or 2.5 mg BD rivaroxaban in this setting (specialist decision)

1. Specific reversal agent availability is limited — andexanet alfa not widely available in India; PCC is the practical option for major bleeding

1. Prior stroke/TIA contraindicates vascular dose — do NOT use rivaroxaban 2.5 mg + aspirin combination in patients with prior stroke or TIA (intracranial bleeding risk)

anticoagulant; DOAC; factor-Xa-inhibitor; rivaroxaban; atrial-fibrillation; DVT; PE; VTE-prophylaxis; CAD; PAD; renal-adjustment; pregnancy-contraindicated; Schedule H

RxIndia v1.0 — 05 Jun 2025

• CDSCO approved product inserts

• Indian Pharmacopoeia

• API Textbook of Medicine

• AIIMS Anticoagulation Protocols

• Cardiological Society of India — AF and VTE management recommendations

• Bayer India Xarelto Prescribing Information

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (supportive)

• EINSTEIN-DVT, EINSTEIN-PE, ROCKET-AF, COMPASS trials (for indication context)

• EINSTEIN-Jr trial (for paediatric off-label context)