Pharmacological Class
- Xanthine oxidase inhibitor
- Non-purine selective inhibitor
- Antihyperuricemic agent
Mechanism of Action
- Inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine → xanthine → uric acid.
- Result: ↓ serum uric acid levels.
- Unlike allopurinol, non-purine structure → less cross-reactivity in patients with allopurinol hypersensitivity.
Clinical Uses in Oncology
- Tumor Lysis Syndrome (TLS) prophylaxis and treatment
- Common in high-risk hematologic malignancies (e.g., acute leukemias, Burkitt lymphoma) undergoing cytotoxic chemotherapy.
- Used when allopurinol is contraindicated or not tolerated.
- Chronic hyperuricemia/gout (less relevant in oncology).
Dosing (Adults)
| Indication | Dose | Notes |
|---|---|---|
| TLS prophylaxis | 40–120 mg orally once daily | Start 1–2 days before chemotherapy; dose adjusted by uric acid response and renal function. |
| Chronic gout | 40–80 mg orally once daily | Titrate as needed to maintain uric acid <6 mg/dL. |
Renal impairment:
- Mild-moderate: no adjustment required.
- Severe (CrCl <30 mL/min): max 80 mg/day.
Hepatic impairment:
- Mild-moderate: caution.
- Severe: not recommended.
- Absorption: Oral, peak ~1 hour.
- Metabolism: Hepatic via UGT1A1, CYP1A2, CYP2C8.
- Half-life: 5–8 hours.
- Excretion: ~50% hepatic (urine and feces).
Adverse Effects
- Common: Liver enzyme elevation (AST, ALT), nausea, rash, headache.
- Serious:
- Cardiovascular events (MI, stroke) – especially in patients with pre-existing CV disease.
- Severe hypersensitivity (rare).
- Monitoring: LFTs at baseline and periodically; monitor uric acid, renal function, electrolytes in TLS patients.
Drug Interactions
- Azathioprine / mercaptopurine: ↑ toxicity (both metabolized by xanthine oxidase); avoid co-administration.
- Theophylline: ↑ levels via CYP1A2 inhibition.
- Warfarin: usually no significant interaction, monitor INR.
- CYP2C8/1A2 substrates: monitor for potential interactions.
Oncology Pearls
- Febuxostat is especially useful in TLS prophylaxis when allopurinol is contraindicated (e.g., HLA-B*5801 positive patients at risk of severe hypersensitivity).
- Unlike allopurinol, febuxostat does not require dose adjustment for mild renal impairment, which is advantageous in oncology patients with fluctuating renal function.
- Monitor uric acid and renal function closely in TLS—goal is to prevent acute kidney injury.
- CV risk should be assessed before use, particularly in elderly oncology patients with cardiovascular comorbidities.