Drug reference

Febuxostat

Xanthine Oxidase Inhibitor · Antigout

Also known as Uloric, Adenuric, Feburic

START

Confirm gout diagnosis and document inadequate response/intolerance to allopurinol. Baseline sUA, creatinine, eGFR, LFTs. Screen for cardiovascular disease history. Start colchicine 0.6 mg daily or NSAID for flare prophylaxis x 6 months. Start 40 mg daily.

TYPICAL MAX

80 mg/day (FDA); 120 mg/day (some guidelines). Reassess if sUA not <6 mg/dL at 80 mg.

STOP IF

Signs of hepatotoxicity (jaundice, dark urine, RUQ pain, ALT >3x ULN), severe hypersensitivity, MI/stroke symptoms, severe gout flare unresponsive to treatment

WATCH

Serum uric acid (target <6 mg/dL), LFTs at baseline and periodically (hepatotoxicity warning), cardiovascular symptoms (chest pain, dyspnea, stroke symptoms), gout flares, skin reactions

CDSCO approvedSchedule HJan AushadhiATC M04AA03

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 19min · absorption onset
PEAK: 1.3h · 1-1.5 h (oral Cmax)
t½: 7h · 5-8 h (mean 7 h)
DURATION: 1d · 24 h (once-daily dosing)

EXCRETION

~49% urine (metabolites); ~45% fecal; extensive hepatic metabolism

route + CYP

INTERACTIONS

8 major

incl. contraindicated

PREGNANCY

FDA PLLR: Limited human data. Animal studies showed fetal harm at high doses. Avoid in pregnancy unless no alternatives. Not recommended during breastfeeding.

FDA category + note

Top interactionssee all 12 →

AzathioprineContraindicatedDatabaseKimi deep-research + Cla
MercaptopurineContraindicatedDatabaseDDInter
TheophyllineContraindicatedDatabaseKimi deep-research + Cla
LeflunomideSevereDatabaseDDInter

Available in India

730 branded formulations. Look up specific brands in the Drugs workspace.

Jan Aushadhi — generic available at GoI pharmacies

Mechanism

Febuxostat is a non-purine selective inhibitor of xanthine oxidase (XO), the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid — the final two steps in uric acid biosynthesis. By inhibiting XO, febuxostat reduces serum uric acid (sUA) production. Unlike allopurinol (a purine analog), febuxostat is a non-purine 2-arylthiazole derivative that does not structurally resemble purines, allowing it to inhibit both the oxidized and reduced forms of xanthine oxidase. It does NOT inhibit other enzymes involved in purine/pyrimidine synthesis at therapeutic concentrations.

Indications

Chronic management of hyperuricemia in patients with goutRecurrent gout with inadequate response or intolerance to allopurinolTumor lysis syndrome prophylaxis (off-label, alternative to allopurinol)

Dosing

Adult: 40 mg PO once daily initially. If sUA >6 mg/dL after 2 weeks: increase to 80 mg PO once daily. Max 120 mg/day (some guidelines). Can be taken with or without food. Prophylactic colchicine or NSAID for gout flare prevention x 6 months.
Pediatric: Not recommended <18 years (safety/efficacy not established).
Renal adjustment: Mild–moderate (CrCl 30–89): no adjustment. Severe renal impairment (CrCl <30): limit to 40 mg once daily (FDA Uloric §2.2). Not dialyzable.
Hepatic adjustment: Mild–moderate (Child-Pugh A/B): no adjustment. Severe (Child-Pugh C): not studied — use with caution; monitor LFTs (FDA — not labelled as contraindicated).
Geriatric: No specific adjustment. Monitor renal function, LFTs, and cardiovascular symptoms.
Max dose: 80 mg/day (FDA-approved); 120 mg/day (some international guidelines)

Pharmacokinetics

Onset

Serum uric acid reduction begins within 24-48 hours; target sUA <6 mg/dL typically achieved within 2 weeks.

Peak effect

Oral: peak plasma at 1-1.5 hours. Steady-state by 7 days.

Duration

24 hours (supports once-daily dosing).

Half-life

5-8 hours (mean ~7 hours). No accumulation at therapeutic doses.

Bioavailability

~49-83% (oral). Food does not significantly affect absorption.

Protein binding

~99.2% (primarily to albumin).

Metabolism

Extensive hepatic metabolism via glucuronidation (UGT1A1, UGT1A3, UGT1A9, UGT2B7 — 22-44% of dose) and oxidation (CYP1A2, CYP2C8, CYP2C9, non-P450 enzymes — 2-8% of dose). Active metabolites (67M-1, 67M-2, 67M-4) are present at much lower concentrations than parent drug.

Excretion

Urine: ~49% (3% unchanged, 30% acyl glucuronide, 13% oxidative metabolites/conjugates, 3% unknown). Feces: ~45% (12% unchanged, 1% glucuronide, 25% oxidative metabolites/conjugates, 7% unknown).

Contraindications

Concurrent use with azathioprine or mercaptopurine (xanthine oxidase substrates — levels increase dramatically causing severe toxicity/myelosuppression)
Concurrent use with theophylline (xanthine oxidase substrate)
Severe hepatic impairment (Child-Pugh C — no data)
History of hypersensitivity to febuxostat

Side effects

Common

NauseaArthralgiaRashLiver function test abnormalities (transient, usually mild)Gout flare (during initiation — expected due to changing urate crystal equilibrium)

Serious

CARDIOVASCULAR DEATH — FDA BLACK BOX WARNING (2019): Higher rate of CV death compared to allopurinol in the CARES trial. Use only in patients with inadequate response/intolerance to allopurinol.
Hepatic failure (sometimes fatal; postmarketing reports — causal relationship cannot be excluded)
Severe hypersensitivity (anaphylaxis, SJS, TEN, DRESS)
Severe gout flare (prophylaxis recommended x 6 months)
Pancytopenia, aplastic anemia (rare)

Pregnancy & lactation

Pregnancy

FDA PLLR: Limited human data. Animal studies showed fetal harm at high doses. Avoid in pregnancy unless no alternatives. Not recommended during breastfeeding.

Lactation

Excretion in breast milk unknown. Due to potential for serious adverse reactions in nursing infants, avoid breastfeeding during febuxostat therapy.

Drug interactions

Azathioprine

Contraindicated

Database

Febuxostat inhibits xanthine oxidase, the enzyme that metabolizes azathioprine and 6-MP to inactive metabolites. Co-administration causes massive increases in azathioprine/6-MP levels, leading to severe myelosuppression, pancytopenia, and hepatotoxicity.

Absolute contraindication. Do NOT use febuxostat in patients on azathioprine or 6-MP. If gout treatment needed, use colchicine, NSAIDs, or allopurinol (also contraindicated with azathioprine — need dose reduction of azathioprine by 50-75%).

Source: Kimi deep-research + Cla

Mercaptopurine

Contraindicated

Database

Increased plasma levels of mercaptopurine.

Concomitant use is contraindicated. If mercaptopurine is essential, an alternative to febuxostat should be considered, or mercaptopurine dose must be drastically reduced (e.g., to 1/10th of the usual dose) with very close monitoring of blood counts, which is generally not recommended due to high risk.

Source: DDInter

Theophylline

Contraindicated

Database

Theophylline is partially metabolized by xanthine oxidase. Febuxostat inhibits this pathway, increasing theophylline levels and risk of toxicity (seizures, arrhythmias, nausea).

Avoid concurrent use. If both needed, use extreme caution, monitor theophylline levels, and reduce theophylline dose.

Source: Kimi deep-research + Cla

Leflunomide

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Lomitapide

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Mipomersen

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Pexidartinib

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Teriflunomide

Severe

Database

Drug interaction classified as: synergy

Source: DDInter

Didanosine

Moderate

Database

Increased risk of didanosine-related adverse effects, including pancreatitis, peripheral neuropathy, and lactic acidosis.

Monitor for didanosine toxicity. Consider reducing didanosine dose or using an alternative agent if toxicity occurs. Close clinical monitoring is warranted.

Colchicine

Moderate

Database

Standard combination for gout flare prophylaxis during febuxostat initiation. Both are commonly co-prescribed. No direct pharmacokinetic interaction, but additive GI effects (nausea, diarrhea) may occur.

Standard of care. Use low-dose colchicine (0.6 mg once or twice daily) for first 6 months. Monitor for GI side effects. Reduce colchicine dose if diarrhea or myopathy develops (especially with renal impairment).

Source: Kimi deep-research + Cla

Hydrochlorothiazide

Moderate

Database

HCTZ can raise serum uric acid by reducing renal urate excretion, potentially antagonizing febuxostat's urate-lowering effect. Also increases risk of hypersensitivity reactions.

Monitor sUA more closely if HCTZ cannot be discontinued. Consider switching to alternative antihypertensive (calcium channel blocker, ACE inhibitor). If sUA remains >6 mg/dL, may need higher febuxostat dose or alternative urate-lowering strategy.

Source: Kimi deep-research + Cla

Nsaids

Moderate

Database

NSAIDs are commonly used for gout flare management. Concurrent use with febuxostat does not have a direct pharmacokinetic interaction, but both affect renal function and cardiovascular risk.

Short-term NSAIDs acceptable for acute flares. Avoid chronic NSAID use due to renal and cardiovascular risks. Monitor renal function and blood pressure.

Source: Kimi deep-research + Cla