Xanthine oxidase inhibitors
ATC code: M04AA01 (Allopurinol)
Brand names
Zyloprim, Aloprim
Xanthine oxidase inhibitor — the enzyme converting hypoxanthine to xanthine and then to uric acid. Reduces uric acid synthesis without affecting renal clearance. Active metabolite oxypurinol has a long half-life (15–30 hours). Effect develops over 1–2 weeks; target uricemia is reached over 3–6 months.
First line
First-line urate-lowering therapy in gout per 2020 and 2017. Indications: recurrent attacks (≥ 2/year), tophi, radiographic gout, urolithiasis. Start 100 mg daily; titrate every 2–5 weeks to a target uric acid below 360 µmol/L (300 in tophaceous gout). Maintenance dose 300–600 mg/day. In Asian patients, mandatory HLA-B*5801 testing before initiation — positive results raise severe cutaneous reaction risk (DRESS, SJS/TEN) 80-fold; use an alternative ().
The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.
Not recommended
Per 2020 and 2017, routine urate-lowering therapy in asymptomatic hyperuricemia is not indicated. Justified only with marked hyperuricemia (above 540 µmol/L) with stone or early CKD risk, and strictly in onco-hematology (tumor lysis syndrome). The widespread practice of prescribing allopurinol 'for high uric acid on labs' without gouty symptoms lacks an evidence base.
Not recommended
Allopurinol is a xanthine oxidase inhibitor. It is prescribed for chronic gout with hyperuricemia and for some conditions with uric acid overproduction (tumor lysis syndrome, uric acid nephrolithiasis) ( 2020, 2023). In sports circles, allopurinol is occasionally promoted to reduce oxidative stress and improve recovery. In athletes without gout or hyperuricemia, no clinical studies of prophylactic use exist. The drug has serious risks: severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS), especially in HLA-B*5801 carriers, hepatotoxicity, and hematological disturbances. If allopurinol was prescribed to an athlete for recovery, consider seeking a second opinion.
5 pairs found. Sorted from critical to minor.
Mechanism
The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). The mechanism is not fully established; presumed to be an immune reaction to metabolites of both drugs in chronic kidney disease.
Symptoms
Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing (Stevens-Johnson syndrome), angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.
Management
Avoid the combination, especially in chronic kidney disease (higher risk). Alternative to ACE-I: an ARB (losartan) for antihypertensive needs. If rash or fever emerges, stop both drugs immediately.
Mechanism
The combination raises risk of hypersensitivity reactions and severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, angioedema). Risk is higher in chronic kidney disease. Mechanism: presumed immune reaction to metabolites of both drugs.
Symptoms
Rash, fever, eosinophilia, lymphadenopathy (DRESS syndrome). Severe cases: bullous rash with skin sloughing, angioedema of face and tongue. Symptoms appear 1–8 weeks into the combination.
Management
Avoid the combination, especially in chronic kidney disease. Alternative to ACE-I: an ARB (losartan, valsartan). If rash or fever emerges, stop both drugs immediately.
Mechanism
Thiazide diuretics raise allopurinol and oxypurinol metabolite levels, increasing hypersensitivity risk, including allopurinol hypersensitivity syndrome (DRESS).
Symptoms
Rash, fever, facial oedema, lymphadenopathy, abnormal liver function. Reactions develop 2–8 weeks after starting allopurinol, more often in older patients and chronic kidney disease.
Management
On the combination, dose allopurinol by creatinine clearance: if below 60 mL/min, start at 100 mg/day with titration of 100 mg every 4 weeks until target uric acid is reached. In Asian patients (especially Han Chinese and Thai), HLA-B*58:01 testing is recommended before starting allopurinol. Alternatives in hyperuricaemia: febuxostat (if no heart failure), or replace the thiazide with losartan (urocosuric effect).
Mechanism
Indapamide (thiazide-like diuretic) raises allopurinol and oxypurinol levels, increasing hypersensitivity risk. The effect is weaker than with hydrochlorothiazide but clinically significant in older patients and chronic kidney disease.
Symptoms
Rash, fever, facial oedema, lymphadenopathy, abnormal liver function. Reactions develop 2–8 weeks after starting allopurinol.
Management
Dose allopurinol by creatinine clearance (start 100 mg/day if clearance below 60 mL/min). In Asian patients, HLA-B*58:01 testing is recommended. In significant hyperuricaemia, replacing indapamide with losartan lowers uric acid by 10–15%.
Mechanism
Allopurinol weakly inhibits CYP2C9 and reduces metabolism of the more active S-warfarin enantiomer. INR may rise by 0.5–1.
Symptoms
Gum bleeding, epistaxis, bruising without trauma, black or tarry stools, haematuria. Higher risk in older patients, prior peptic ulcer disease, and chronic kidney disease.
Management
On allopurinol initiation or dose increase, check INR at 1 and 2 weeks. If outside target, reduce warfarin by 10%.
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FDA categories were retired in 2015. Data are limited. Gout in pregnancy is rare — most reproductive-age patients with hyperuricemia do not require therapy. Severe disease is managed with a rheumatologist.
Transfers into milk. Per LactMed, use is acceptable with infant monitoring.
Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.
Allopurinol is evaluated for the following indications with varying evidence strength: Gout (evidence tier A), Asymptomatic hyperuricemia (evidence tier F), Athletic endurance (evidence tier F). See the full indication matrix with dosing and citations above on this page.
Common side effects of Allopurinol (≥ 1 in 100): Skin rash (1–5 % — most mild but warrants reassessment), Nausea, dyspepsia, Diarrhea, Transient transaminase elevation. See the Safety section for uncommon and serious reactions.
FDA category C. FDA categories were retired in 2015. Data are limited. Gout in pregnancy is rare — most reproductive-age patients with hyperuricemia do not require therapy. Severe disease is managed with a rheumatologist.
Transfers into milk. Per LactMed, use is acceptable with infant monitoring.
Allopurinol is contraindicated in: Hypersensitivity; Severe hepatic impairment; Severe renal impairment (requires dose adjustment); Acute gout attack at the moment of initiation (start 2 weeks after attack resolution). Full list in the Safety section.