Generic Name

Febuxostat

Mechanism

• Febuxostat competitively binds the active site of xanthine oxidase, blocking the oxidation of xanthine to uric acid.
• Unlike allopurinol, it does not require metabolic activation, allowing consistent inhibition even at high urate levels.
• By lowering serum urate, it reduces crystal deposition and prevents gout flares.

Pharmacokinetics

• Absorption: Rapid, 80–85 % bioavailability; peak plasma concentration 1–4 h post‑dose.
• Distribution: Extensive tissue binding; mean volume of distribution 30–35 L.
• Metabolism: Primarily hepatic via CYP2C8 and CYP2C9; minor glucuronidation.
• Excretion: ~50 % unchanged in urine, 30–35 % via bile; elimination half‑life ~40 h.
• Not clinically affected by mild‑to‑moderate renal impairment; dose adjustment not required.

Indications

• Chronic gout with inadequate response to or intolerance of allopurinol.
• Primary hyperuricemia in patients with a history of gout or kidney disease.
• Secondary hyperuricemia (e.g., due to tumor lysis syndrome) when xanthine oxidase inhibition is needed.

Contraindications

• Known hypersensitivity to febuxostat or any excipient.
• Severe hepatic impairment (Child‑Pugh class C).
• Active liver disease; monitor serum transaminases ≥3 × ULN prior to therapy and monthly initially.
• Sulfinpyrazone users: avoid concomitant use due to increased CYP inhibition.
• Pregnancy: Category C; use only if clearly needed.
• Concurrent steroid use: may mask flare on initiation; monitor clinical response.

Dosing

• Oral capsule, 20 mg or 40 mg once daily.
• Start at 20 mg; titrate to 40 mg if serum urate remains >6 mg/dL after 1–2 months.
• Can be taken with or without food; dose should be the same day (avoid 6‑hr interval changes).
• For patients on allopurinol discontinuation, wait 2 weeks if on a high‑dose allopurinol to avoid a flare.
• Renal dosing adjustment: none required for CrCl >30 mL/min.

Adverse Effects

• Common: nausea, diarrhea, headache, rash, arthralgia.
• Serious: hepatotoxicity (↑AST/ALT >3 × ULN), hypersensitivity rash, interstitial lung disease (rare).
• Cardiac: monitor for potential QT prolongation; not a major concern but noted in post‑marketing.
• Other: elevated creatinine (usually reversible) due to reduced uric acid excretion.

Monitoring

• Baseline and monthly LFTs (AST, ALT, bilirubin).
• Serum urate every 1–2 months after dose titration until stable.
• Renal function quarterly (eGFR/CrCl).
• Blood pressure and heart rate if cardiovascular comorbidity present.
• Watch for flare signs; consider prophylactic colchicine or NSAIDs during initiation.

Clinical Pearls

• “No safe dose?” Even patients with CrCl 3 × ULN) predicts severe hepatotoxicity, thus discontinuation is advised.
• Clinical synergy: Combine with colchicine or NSAIDs when initiating to blunt flare incidence, especially in patients with a history of chronic flare.
• Therapeutic monitoring: If serum urate remains >6 mg/dL despite 40 mg dosing, consider adjunctive therapy (e.g., uricosuric agents) rather than increasing dose beyond 40 mg due to limited benefit.

This concise drug card equips students and clinicians with high‑yield, actionable information on febuxostat while optimizing for search visibility with relevant pharmacology keywords.