allopurinol
Brand: Zyloprim, Lopurin
Prototype Drug
Drug Class: xanthine oxidase inhibitor
Drug Family: uric acid agent
Subclass: urate-lowering agent
Organ Systems: endocrinemusculoskeletal
Mechanism of Action
Inhibits xanthine oxidase, the enzyme that catalyzes the final two steps of uric acid synthesis (hypoxanthine→xanthine→urate). Allopurinol and its active metabolite oxypurinol both inhibit XO, reducing uric acid production and lowering serum and urinary urate levels.
xanthine oxidase (XO)
Indications
- gout (prevention of attacks — urate-lowering therapy)
- uric acid nephrolithiasis
- tumor lysis syndrome (prophylaxis)
- hyperuricemia (secondary causes)
Contraindications
- hypersensitivity to allopurinol
- do not use in HLA-B*5801 positive patients (high risk for SJS/TEN — common in Han Chinese, Korean, Thai populations)
Adverse Effects
Common
- rash (especially maculopapular — drug should be discontinued at any rash)
- nausea
- diarrhea
- headache
Serious
- Stevens-Johnson syndrome / TEN (rare but potentially fatal; strongly associated with HLA-B*5801)
- DRESS syndrome (drug reaction with eosinophilia and systemic symptoms)
- allopurinol hypersensitivity syndrome (AHS)
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~80% |
| Distribution | low protein binding (~1%); widely distributed |
| Metabolism | metabolized to oxypurinol (active) by xanthine oxidase |
| Excretion | renal (70% as oxypurinol) |
| Half-life | 1–3 hours (allopurinol); 12–30 hours (oxypurinol) |
| Onset | days to weeks |
| Peak | 1.5 hours |
| Duration | continuous |
| Protein Binding | ~1% |
| Vd | 1.6 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| azathioprine or 6-mercaptopurine | xanthine oxidase inhibition dramatically increases 6-MP/azathioprine levels; fatal myelosuppression; dose must be reduced 75% | major |
| ampicillin, amoxicillin | increased incidence of allopurinol-associated rash | moderate |
| warfarin | allopurinol inhibits hepatic metabolism; increases anticoagulant effect | major |
Nursing Considerations
- Discontinue immediately at the first sign of rash — even a macular rash may be the first sign of SJS/DRESS; do not restart after discontinuation for rash.
- HLA-B*5801 genetic testing is recommended in patients of Han Chinese, Korean, Thai, or Vietnamese ancestry before initiating allopurinol.
- Do not initiate during acute gout attack; begin after attack resolves; initiation can precipitate an acute gout flare — provide colchicine or NSAID prophylaxis for 3–6 months.
- Reduce dose in renal impairment as oxypurinol accumulates; dose adjustment based on CrCl.
Clinical Pearls
- The azathioprine-allopurinol interaction is one of the most dangerous in clinical practice: allopurinol blocks xanthine oxidase, the primary elimination pathway for azathioprine's active metabolites, causing up to 10-fold accumulation and potentially fatal myelosuppression.
- The HLA-B*5801 allele is found in 6–8% of Han Chinese patients and is associated with an approximately 100-fold increased risk of allopurinol-induced SJS/TEN; pharmacogenomic testing before prescribing is now recommended in relevant populations.
Safety Profile
Pregnancy use-with-caution
Lactation avoid
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.