Schedule H

Oral

• Tablets: 40 mg, 80 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Chronic Hyperuricaemia in Gout (Urate Crystal Deposition Disease)

Step Dose Clinical Notes

Starting dose 40 mg once daily Administer without regard to food

Titration Increase to 80 mg once daily if serum uric acid >6 mg/dL after 2–4 weeks Target serum uric acid <6 mg/dL

Usual maintenance dose 40–80 mg once daily Based on uric acid response

Maximum dose 80 mg once daily Higher doses not approved in India

Key points:

• Co-prescribe colchicine (0.5 mg once or twice daily) or NSAID prophylaxis for at least 6 months to prevent mobilisation flares

• Do NOT initiate during acute gout flare — wait until attack resolves

• Not indicated for asymptomatic hyperuricaemia without clinical manifestations of gout

Secondary Indications — Adults (Off-label)

Indication Dose Duration Notes

Tumour Lysis Syndrome prophylaxis 120 mg once daily Start 2 days before cytotoxic therapy; continue up to 7 days OFF-LABEL; Specialist only; Evidence: FLORENCE trial (RCT); used when rasburicase unavailable or contraindicated

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

Not applicable.

Febuxostat is not approved for use in children and adolescents below 18 years of age in India. Safety and efficacy data in paediatric population are insufficient.

Secondary Indications — Paediatrics (Off-label)

Not applicable.

No established paediatric dosing guidelines exist. Use only under paediatric rheumatology or oncology specialist supervision if absolutely necessary and no alternatives are available.

Note: Febuxostat offers advantage over allopurinol in moderate renal impairment as significant dose reduction is not required

• Known hypersensitivity to febuxostat or any excipients

• Concurrent use with azathioprine or 6-mercaptopurine (risk of fatal myelosuppression)

• Acute gout attack (do not initiate during flare; defer until resolution)

• Established ischaemic heart disease or congestive heart failure (US FDA boxed warning; exercise caution in Indian practice — evaluate cardiovascular status before initiation)

• History of cardiovascular disease or multiple CV risk factors — increased risk of cardiovascular death reported in CARES trial; use only after careful risk-benefit evaluation

• Acute gout flare during treatment — do NOT discontinue febuxostat; continue drug and manage flare with colchicine/NSAIDs

• Hepatic transaminase elevation — monitor LFTs periodically

• Thyroid disorders — may affect thyroid function tests

• Asymptomatic hyperuricaemia — avoid treatment unless clinically indicated

• Renal transplant recipients — limited data; use with caution

Parameter Recommendation

Safety category Limited human data; animal studies show fetal harm — avoid use

Preferred alternatives Allopurinol (only if essential and under specialist guidance); dietary modification preferred

When it may be used Only when no alternatives exist and benefit clearly outweighs risk; requires specialist obstetric input

Monitoring Maternal uric acid levels, renal function; fetal growth surveillance if used

Parameter Recommendation

Compatibility Not recommended — excretion in human milk unknown

Drug levels in milk Unknown (animal studies suggest excretion)

Preferred alternatives Allopurinol with caution; preferably avoid urate-lowering therapy during lactation if possible

Infant monitoring If unavoidable, observe infant for gastrointestinal disturbances, rash, poor weight gain

• Recommended starting dose: 40 mg once daily

• Titration: Slower titration recommended; reassess at 4 weeks before dose escalation

• Additional risks:

• Higher prevalence of cardiovascular comorbidities — evaluate CV risk before initiation

• Age-related decline in renal function — assess eGFR; may require conservative dosing

• Polypharmacy concerns — review for drug interactions

• Monitoring: Regular cardiovascular assessment, renal function, and LFTs

Drug Interaction Management

Azathioprine / 6-Mercaptopurine Febuxostat inhibits xanthine oxidase, causing marked increase in thiopurine levels → severe or fatal myelosuppression CONTRAINDICATED — do not use together

Theophylline Increased theophylline plasma concentration due to xanthine oxidase inhibition Avoid combination; if unavoidable, monitor theophylline levels closely

Didanosine Enhanced didanosine toxicity Avoid combination

Drug Interaction Management

Warfarin Possible minor effect on INR Monitor INR when initiating or stopping febuxostat

NSAIDs Commonly co-administered for flare prophylaxis; additive renal effects possible Monitor renal function; ensure adequate hydration

Hydrochlorothiazide May elevate uric acid levels, potentially reducing febuxostat efficacy Monitor serum uric acid; may need dose adjustment

Rosiglitazone Febuxostat inhibits CYP2C8, potentially increasing rosiglitazone exposure Monitor for hypoglycaemia; adjust dose if needed

Colchicine Commonly co-prescribed; additive GI side effects Monitor for diarrhoea; adjust colchicine dose if significant GI upset

• Gout flares (particularly during first few months of treatment)

• Liver enzyme elevations (transaminases)

• Nausea

• Diarrhoea

• Headache

• Arthralgia

• Rash

Reaction Action Required

Cardiovascular events (myocardial infarction, stroke, cardiovascular death) Discontinue if event occurs; do not initiate in patients with established CVD

Stevens-Johnson Syndrome / Toxic Epidermal Necrolysis Discontinue immediately; hospitalise

Severe hepatotoxicity Discontinue; monitor LFTs; hepatology referral if severe

DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms) Discontinue immediately; hospitalise

Anaphylaxis / severe hypersensitivity Discontinue permanently; emergency management

Note: Patients should be counselled to report any skin rash, chest pain, or unexplained symptoms promptly

At 2–4 weeks Serum uric acid (to guide dose titration)

During first 6 months Clinical monitoring for gout flares; ensure prophylaxis continued

Long-term LFTs every 3–6 months; serum uric acid every 6–12 months; periodic cardiovascular evaluation

Clinical note: Discontinue and evaluate if transaminases exceed 3× upper limit of normal or if any rash develops

• Feburic (Sun Pharma)

• Febuxostat (generic — multiple manufacturers)

• Zurig (Zydus Cadila)

• Febutaz (Lupin)

• Fabulas (Intas)

• Goutnil-F (Alkem)

• Febuget (Mankind)

NLEM status: Not included in NLEM 2022 — not under NPPA price ceiling

Jan Aushadhi: Available as Febuxostat 40 mg at subsidised rates

• Cardiovascular caution: CARES trial showed increased cardiovascular mortality vs allopurinol; avoid in patients with established CVD; prefer allopurinol as first-line unless contraindicated or not tolerated

• Renal advantage: Febuxostat does not require significant dose reduction in mild-moderate CKD, unlike allopurinol — may be preferred in renal impairment

• Never stop during flare: Continue febuxostat if acute gout develops during treatment; manage flare with colchicine or NSAIDs

• Flare prophylaxis is essential: Co-prescribe low-dose colchicine or NSAID for at least 6 months to prevent mobilisation flares

• Azathioprine interaction is life-threatening: Absolutely contraindicated with azathioprine or 6-mercaptopurine — severe bone marrow suppression

• Start low: Begin at 40 mg; escalate only if target uric acid (<6 mg/dL) not achieved after 2–4 weeks

gout; hyperuricaemia; xanthine oxidase inhibitor; uric acid lowering; cardiovascular risk; renal-safe (moderate CKD); azathioprine interaction; rheumatology; TLS prophylaxis

RxIndia v1.1 — 14 Jun 2025

• CDSCO Approved Product Information

• Indian Pharmacopoeia 2022

• API Textbook of Medicine (11th Edition)

• AIIMS Standard Treatment Guidelines

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)

• Harrison's Principles of Internal Medicine (21st Edition)

• CARES Trial (N Engl J Med 2018) — for cardiovascular risk data (off-label safety reference)

• FLORENCE Trial — for TLS prophylaxis evidence (off-label indication)