Allopurinol

Pharmacological Class

• Xanthine oxidase inhibitor
• Purine analog
• Antihyperuricemic agent

Mechanism of Action

• Allopurinol is a purine analog that inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine → xanthine → uric acid.
• Result: decreased uric acid production, preventing uric acid accumulation.
• Its active metabolite oxypurinol contributes to prolonged activity, especially in renal impairment.

Clinical Uses in Oncology

1. Tumor Lysis Syndrome (TLS) prophylaxis
   • High-risk patients: acute leukemias, high-burden lymphomas (e.g., Burkitt lymphoma).
   • Used to prevent hyperuricemia and subsequent renal injury during cytotoxic chemotherapy.
2. Chronic hyperuricemia / gout (less relevant in oncology).
3. Sometimes used pre-chemotherapy in patients with elevated baseline uric acid.

Dosing (Adults)

Renal impairment:

• Dose adjustment required. For example:
  • CrCl 10–20 mL/min: 50 mg daily
  • CrCl <10 mL/min: 50 mg every 2–3 days or per oxypurinol level monitoring

Hepatic impairment:

• Generally no adjustment needed; monitor liver function.

Pharmacokinetics

• Absorption: Oral, 80–90% bioavailability
• Peak: 1–2 hours
• Metabolism: Hepatic to oxypurinol (active metabolite)
• Half-life: Allopurinol ~1–2 h; oxypurinol ~18–30 h (renal excretion)
• Excretion: Mainly renal; accumulates in renal impairment

Adverse Effects

• Common: Rash, nausea, diarrhea, LFT elevations.
• Serious:
  • Allopurinol hypersensitivity syndrome (AHS): fever, rash, eosinophilia, renal/hepatic dysfunction; often fatal if untreated. Risk higher in HLA-B*5801 carriers (especially Asian populations).
  • Severe cutaneous reactions (Stevens–Johnson syndrome, toxic epidermal necrolysis)
• Other: Rare myelosuppression, hepatotoxicity

Drug Interactions

• Azathioprine / Mercaptopurine: xanthine oxidase inhibition → increased toxicity. Dose reduction required (~25–33%).
• Theophylline: ↑ serum levels
• Warfarin: generally minimal, monitor INR
• Chemotherapy agents: monitor for additive toxicity (renal or hepatic)

Monitoring in Oncology

• Serum uric acid: ensure goal <7 mg/dL before chemotherapy
• Renal function: especially in TLS patients
• LFTs: baseline and periodically
• CBC: monitor if high-dose therapy or combined with myelosuppressive agents
• Watch for hypersensitivity: especially in high-risk populations

Oncology Pearls

• Allopurinol is first-line for TLS prophylaxis in most patients with adequate renal function and low to moderate TLS risk.
• Febuxostat may be preferred if allopurinol allergy or HLA-B*5801 positivity.
• Rasburicase is preferred in high-risk TLS (very high uric acid or rapidly proliferating tumors) due to its ability to rapidly degrade uric acid.
• Renal dose adjustment is essential, as oxypurinol accumulation can cause toxicity.

If you want, I can make a side-by-side table comparing Allopurinol, Febuxostat, and Rasburicase for TLS management specifically for oncology pharmacists. This is extremely useful in practice.

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