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
- 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.
- Chronic hyperuricemia / gout (less relevant in oncology).
- Sometimes used pre-chemotherapy in patients with elevated baseline uric acid.
Dosing (Adults)
| Indication | Dose | Notes |
|---|---|---|
| TLS prophylaxis | 100–300 mg orally daily; may titrate to uric acid <7 mg/dL | Start 1–2 days before chemotherapy; increase gradually. |
| Chronic hyperuricemia | 100–800 mg daily (divided doses) | Titrate based on serum uric acid. |
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.
- 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.