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Research · Medication

Allopurinol

Allopurinol lowers blood uric acid: in one trial 25 of 26 people reached the target in 30 days against none on placebo. Gout flares eased only with continued treatment. Trials found no slowing of kidney disease and no fewer heart events. The label reports severe skin reactions in about 5 in 10,000 people.

Add to Bio HackChecked 2026-11-13
Status
Prescription drug in the US. FDA-approved to manage gout in adults, high uric acid during cancer therapy in adults and children, and recurrent calcium oxalate kidney stones in adults with high urinary uric acid. The label carries a limitation of use for high uric acid without symptoms and no boxed warning.
Also called
Zyloprim, Aloprim, Lopurin, xanthine oxidase inhibitor, urate-lowering therapy, gout medicine
Taken for
gout, high uric acid, gout flare prevention, tophi, kidney stones, tumor lysis syndrome, kidney protection, heart protection, blood pressure

Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on

Shown to help5

Reported risks8

What people take it for, and what was found

Shown to help5

ModerateVery common

Lowering uric acid in gout

Shown to lower blood uric acid, with 25 of 26 people on 300 mg a day reaching the target within 30 days against none of 25 on placebo.

The numbers and sources
How common
Very common: more than 1 in 10 people.
Effect
In the one placebo-controlled trial in a Cochrane review, 25 of 26 people on allopurinol 300 mg a day reached the target serum urate over 30 days against 0 of 25 on placebo [1]. At a fixed 300 mg a day for 52 weeks, 21% had urate below 6.0 mg/dL at the last three monthly measurements [2]. When the dose was raised step by step, 69% had urate below 6 mg/dL at 12 months against 32% of those left on their starting dose, with mean changes of -1.5 and -0.34 mg/dL [3]. In a 72-week trial that raised doses toward a urate target, 80% reached it on allopurinol or febuxostat with no difference between them [4].
Population
4,531 participants in 11 trials, 2 of them placebo-controlled [1]; 760 people with gout and urate of at least 8.0 mg/dL [2]; 183 people with gout already on allopurinol, 52% with reduced kidney function [3]; 940 people with gout, at least a third with stage 3 chronic kidney disease [4].
Sources
[1], [2], [3], [4]
Caveats
The placebo comparison rests on one trial of 57 people [1]. The share reaching target depended on whether the dose was fixed or raised [2][3].
Limited

Uric acid during cancer treatment

One trial found 66% of adults at risk of tumor lysis syndrome kept uric acid controlled on allopurinol, against 87% on rasburicase.

The numbers and sources
Effect
In adults with blood cancers, plasma uric acid stayed at or fell to 7.5 mg/dL or below during days 3 to 7 in 66% on oral allopurinol 300 mg a day, 87% on intravenous rasburicase and 78% on rasburicase followed by allopurinol. In those who started with high uric acid, control took 27 hours on allopurinol and 4 hours on rasburicase [7].
Population
275 adults with blood cancers at risk of high uric acid and tumor lysis syndrome, 91 of them on allopurinol alone [7].
Sources
[7]
Caveats
One trial with no placebo group, measuring uric acid and not kidney injury.
Limited

Preventing calcium oxalate kidney stones

One trial found fewer kidney stone events on allopurinol, 0.12 against 0.26 per patient a year, in people with high urinary uric acid.

The numbers and sources
Effect
In people with recurrent calcium oxalate stones, high urinary uric acid and normal urinary calcium, stone events occurred at 0.12 per patient a year on allopurinol 100 mg three times a day and 0.26 on placebo, and time to recurrence was longer on allopurinol. Against their own history, stones fell 81.2% on allopurinol and 63.4% on placebo [8].
Population
60 people with a history of calcium oxalate stones [8].
Sources
[8]
Caveats
One small trial from 1986. Stones also fell 63.4% in the placebo group, which the authors attribute to the bias of comparing people against their own history [8].
Limited

Exercise time in stable angina

One crossover trial found high-dose allopurinol lengthened exercise time before ECG changes by 43 seconds against placebo in people with stable angina.

The numbers and sources
Effect
On allopurinol 600 mg a day for 6 weeks, median time to ST depression on a treadmill test rose from 232 to 298 seconds, against 249 seconds on placebo, a difference of 43 seconds (95% CI 31 to 58). Total exercise time was 58 seconds longer (95% CI 45 to 77) and time to chest pain 38 seconds longer (95% CI 17 to 55) [13].
Population
65 adults with coronary artery disease and stable angina, 60 analyzed in both periods [13].
Sources
[13]
Caveats
One small trial of 6 weeks. A later trial of 5,721 people with ischemic heart disease found no fewer cardiovascular events [11].
Moderate

Blood pressure

Shown to lower blood pressure by about 3.3/1.3 mm Hg across 10 studies, with larger falls in one trial of adolescents with high uric acid.

The numbers and sources
Effect
Across 10 studies, systolic pressure fell 3.3 mm Hg more on allopurinol than control (95% CI 1.4 to 5.3) and diastolic 1.3 mm Hg (95% CI 0.1 to 2.5), with similar results in the higher-quality randomized trials [14]. In adolescents with newly diagnosed hypertension and uric acid of 6 mg/dL or more, 4 weeks of allopurinol lowered clinic systolic pressure by 6.9 mm Hg against 2.0 on placebo and diastolic by 5.1 against 2.4. Twenty of 30 reached normal blood pressure on allopurinol and 1 on placebo [15].
Population
738 participants in 10 studies [14]; 30 adolescents aged 11 to 17 in a crossover trial [15].
Sources
[14], [15]
Caveats
Small studies. Not an FDA-approved use [5].

Mixed results1

Moderate

Gout flares

Mixed results: no fewer gout attacks than placebo over 30 days in one small trial, and flares became less frequent with continued treatment in longer trials.

The numbers and sources
Effect
Over 30 days, gout attacks occurred in 2 of 26 people on allopurinol 300 mg and 3 of 25 on placebo (RR 0.64, 95% CI 0.12 to 3.52) [1]. Over weeks 9 to 52 of a year-long trial, 64% on allopurinol had a flare, and the incidence fell with continued treatment [2]. In the final 24 weeks of a 72-week trial, 36.5% on allopurinol had one or more flares against 43.5% on febuxostat, meeting the test for noninferiority [4]. The label states that gout attacks usually become shorter and less severe after several months of treatment [5].
Population
51 people in the placebo-controlled trial [1]; 760 people with gout [2]; 940 people with gout [4].
Sources
[1], [2], [4], [5]
Caveats
The longer trials had no placebo group, so the fall in flares over time has no untreated comparison [2][4].

Not shown to help4

Moderate

Compared with febuxostat

Not shown to differ from febuxostat in gout flares or major cardiovascular events. One trial found fewer deaths on allopurinol.

The numbers and sources
Effect
Across 3 trials, gout attacks over 8 to 24 weeks occurred in 21% on allopurinol up to 300 mg and 23% on febuxostat 80 mg (RR 0.89, 95% CI 0.71 to 1.1) [1]. At fixed doses, 21% on allopurinol 300 mg reached the urate target against 53% and 62% on febuxostat 80 and 120 mg, with flares over weeks 9 to 52 in 64%, 64% and 70% [2]. With doses raised to target, flares in the last phase were 36.5% on allopurinol and 43.5% on febuxostat [4]. In people with gout and cardiovascular disease, the main cardiovascular outcome occurred in 10.4% on allopurinol and 10.8% on febuxostat (HR 1.03), and death from any cause was more frequent on febuxostat (HR 1.22, 95% CI 1.01 to 1.47), as was cardiovascular death (HR 1.34, 95% CI 1.03 to 1.73) [6].
Population
1,136 participants in 3 trials [1]; 760 people with gout [2]; 940 people with gout [4]; 6,190 people with gout and cardiovascular disease followed a median of 32 months [6].
Sources
[1], [2], [4], [6]
Caveats
In the cardiovascular trial 56.6% stopped the study drug and 45.0% left follow-up [6].
Moderate

Slowing chronic kidney disease

Not shown to slow loss of kidney function in two placebo-controlled trials, in chronic kidney disease and in type 1 diabetes.

The numbers and sources
Effect
In adults with stage 3 or 4 chronic kidney disease, eGFR fell 3.33 mL/min/1.73 m² a year on allopurinol and 3.23 on placebo (difference -0.10, 95% CI -1.18 to 0.97) [9]. In people with type 1 diabetes and early kidney disease, serum urate fell from 6.1 to 3.9 mg/dL on allopurinol and stayed at 6.1 on placebo. Measured GFR after 3 years and a washout did not differ (difference 0.001, 95% CI -1.9 to 1.9), and urinary albumin excretion was 40% higher on allopurinol (95% CI 0 to 80) [10].
Population
363 adults with chronic kidney disease, no gout and a mean eGFR of 31.7, followed 104 weeks [9]; 530 people with type 1 diabetes and a GFR of 40 to 99.9 [10].
Sources
[9], [10]
Caveats
The first trial stopped recruiting early, at 369 of a planned 620 people [9].
Limited

Heart attack, stroke and cardiovascular death

One trial found allopurinol did not lower heart attack, stroke or cardiovascular death in adults aged 60 or older with ischemic heart disease and no gout.

The numbers and sources
Effect
Over a mean of 4.8 years, nonfatal heart attack, nonfatal stroke or cardiovascular death occurred in 11.0% on allopurinol up to 600 mg a day and 11.3% on usual care (HR 1.04, 95% CI 0.89 to 1.21). Death from any cause was 10.1% against 10.6% (HR 1.02, 95% CI 0.87 to 1.20) [11].
Population
5,721 UK adults aged 60 or older with ischemic heart disease and no history of gout, mean age 72 [11].
Sources
[11]
Caveats
Open label with no placebo, with outcomes assessed blind to treatment [11].
Why limited
This rests on one trial, of 5,721 people. Strength counts independent studies that agree, so one trial is limited at any size.
Limited

Heart failure

One trial found allopurinol did not improve clinical status, walking distance or quality of life over 24 weeks in heart failure with high uric acid.

The numbers and sources
Effect
At 24 weeks, clinical status had worsened in 45% on allopurinol and 46% on placebo and improved in 13% and 19%. Quality of life scores, 6-minute walk distance and ejection fraction did not differ. Uric acid was lower on allopurinol by 4.2 mg/dL at 12 weeks and 3.5 mg/dL at 24 weeks [12].
Population
253 people with symptomatic heart failure, an ejection fraction of 40% or below and uric acid of at least 9.5 mg/dL [12].
Sources
[12]
Caveats
One trial of 24 weeks, at a target dose of 600 mg a day.

Doses studied

For gout, the label describes a starting dose of 100 mg a day, raised by 100 mg a week until serum uric acid is 6 mg/dL or below, up to 800 mg a day, with lower starting doses in kidney impairment. For cancer therapy it gives 300 to 800 mg a day in adults, and for kidney stones the trial dose was 100 mg three times a day [5][8].

The gout trials used a fixed 300 mg a day or raised the dose from 100 mg toward a urate target, to as much as 800 mg [2][4]. The kidney disease trial used 100 to 300 mg a day, the heart disease trial up to 600 mg, the angina trial 600 mg and the adolescent blood pressure trial 200 mg twice a day [9][11][13][15].

Risks

Reported risks8

LimitedCommon

Skin rash

One trial found rash in 10% on allopurinol against 2% on placebo. The label calls skin rash the most frequent adverse reaction.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
In a heart failure trial at a target dose of 600 mg a day, rash occurred in 10% on allopurinol and 2% on placebo [12]. The label states that the most frequent adverse reaction is skin rash, lists rash at 1% or more, and directs that the drug be stopped at the first appearance of a rash or other sign that may indicate a hypersensitivity reaction [5].
Population
253 people with heart failure and high uric acid [12].
Sources
[12], [5]
Caveats
One trial at a high dose in people with heart failure. The label gives no placebo rate.
LimitedCommon

Gout flares when starting

The label warns that gout flares can occur when allopurinol is started, even as uric acid falls, and lists acute gout attacks at 1% or more.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The label states that flares have been reported during initiation, even when normal or low serum uric acid has been reached, because urate is mobilized from tissue deposits, and that it may take several months to control flares. It lists acute attacks of gout among reactions occurring in 1% or more [5]. In a year-long trial that gave naproxen or colchicine for the first 8 weeks, 64% on allopurinol still had a flare during weeks 9 to 52 [2].
Population
People with gout starting allopurinol, as described in the label [5]; 760 people with gout [2].
Sources
[5], [2]
Caveats
The trial had no placebo group, and people with gout have flares without treatment. The band here is the label's 1% or more.
LimitedCommon

Liver enzymes and liver injury

The label reports rises in AST, ALT and alkaline phosphatase in 1% or more of people, and cases of reversible liver injury.

The numbers and sources
How common
Common: between 1 in 100 and 1 in 10 people.
Effect
The label lists increases in AST, ALT and alkaline phosphatase among reactions occurring in 1% or more, and states that cases of reversible liver injury have occurred, with hepatic necrosis and granulomatous hepatitis reported in under 1% [5]. In a dose-escalation trial, mild rises in liver tests were frequent in both the escalation and control groups [3].
Population
People taking allopurinol, as described in the label [5]; 183 people with gout [3].
Sources
[5], [3]
Caveats
The label gives no placebo rate and no size for the enzyme rises.
ModerateRare

Severe skin reactions and hypersensitivity

The label warns of serious and sometimes fatal skin reactions in about 5 in 10,000 people, with higher risk in carriers of the HLA-B*58:01 gene.

The numbers and sources
How common
Rare: fewer than 1 in 1,000 people.
Effect
The label states that toxic epidermal necrolysis, Stevens-Johnson syndrome and drug reaction with eosinophilia and systemic symptoms occur in about 5 in 10,000 (0.05%) people taking allopurinol, mostly in the first few months, and that the HLA-B58:01 allele, more frequent in people of African, Asian and Native Hawaiian or Pacific Islander ancestry, marks higher risk [5]. In Taiwan, hypersensitivity occurred in 4.68 per 1,000 new users a year, related hospitalization in 2.02 and related death in 0.39, with higher risk in women, people 60 or older, starting doses above 100 mg a day, kidney or cardiovascular disease, and use for high uric acid without symptoms [16]. In Han Chinese, all 51 people with a severe reaction carried HLA-B5801, against 15% of 135 who tolerated the drug [17]. Pooled across 4 studies the odds ratio for Stevens-Johnson syndrome or toxic epidermal necrolysis in carriers was 96.60 (95% CI 24.49 to 381.00) [18]. In a case-control study, 91% of people with hypersensitivity syndrome and 36% of controls had started at 1.5 mg or more per unit of estimated GFR [19].
Population
495,863 new users in Taiwan's national insurance database [16]; 51 cases and 228 controls [17]; 55 cases and 678 matched controls in 4 studies [18]; 54 cases and 157 controls [19].
Sources
[5], [16], [17], [18], [19]
Caveats
The cohort rate covers all hypersensitivity, a wider group than the severe skin reactions in the label's figure, and comes from a population where the allele is frequent [16]. The band here is taken from the label's 0.05%. The label notes reactions also occur in people without the allele [5].
LimitedHow often is not known

With azathioprine and mercaptopurine

The label warns that allopurinol raises exposure to azathioprine and mercaptopurine, which can suppress the bone marrow.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that allopurinol blocks the breakdown of mercaptopurine and azathioprine, raising exposure to either and the risk of bone marrow suppression, and that a reduced dose of those drugs is required. It also reports anemia, low white cells and low platelets on allopurinol itself, from 6 weeks to 6 years after starting, and higher cyclosporine levels when the two are combined [5].
Population
People taking these drugs together, as described in the label [5].
Sources
[5]
Caveats
The label gives no rate.
LimitedHow often is not known

With blood thinners, diuretics and some antibiotics

The label warns that allopurinol may strengthen warfarin, and that thiazide diuretics, ampicillin and amoxicillin may raise the risk of skin rash.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that allopurinol may inhibit the metabolism of warfarin and enhance its anticoagulant effect. It states that thiazide diuretics, ampicillin, amoxicillin and bendamustine may raise the risk of skin rash, which may be severe, more so with thiazides in kidney impairment. It also lists interactions with theophylline at 600 mg a day or more, chlorpropamide, capecitabine and pegloticase [5].
Population
People taking these drugs together, as described in the label [5].
Sources
[5]
Caveats
The label gives no rate.
LimitedHow often is not known

Kidney injury from xanthine stones

The label warns that allopurinol may cause acute kidney injury through xanthine stones, with higher risk in people who already have kidney disease or stones.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that treatment may result in acute kidney injury from xanthine stones, or from urate precipitation in people also taking uricosuric drugs, and that people with chronic kidney disease or a history of kidney stones may be at higher risk [5]. In a trial in chronic kidney disease, kidney function loss did not differ from placebo over 104 weeks [9].
Population
People taking allopurinol, as described in the label [5]; 363 adults with chronic kidney disease [9].
Sources
[5], [9]
Caveats
The label gives no rate.
LimitedStudied in pregnancyHow often is not known

Use in pregnancy

The label states that allopurinol may cause fetal harm based on animal findings, with 2 major malformations among about 50 published pregnancies.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
The label states that, based on findings in animals, allopurinol may cause fetal harm, and that it crosses the placenta. Among about 50 pregnancies in the published literature, 2 infants with major congenital malformations were reported, which the label says shows no clear pattern or increase [5].
Population
About 50 published pregnancies with allopurinol exposure [5].
Sources
[5]
Caveats
Published case reports, with no comparison group.

Checked, no increase found1

Moderate

Serious adverse events overall

Not shown to raise serious adverse events against placebo in kidney disease and heart failure trials, 46% against 44% in one and 20% against 15% in another.

The numbers and sources
How common
How often is not known: the sources give no rate.
Effect
Serious adverse events were reported in 46% on allopurinol and 44% on placebo in the chronic kidney disease trial [9], and in 20% against 15% in the heart failure trial (p = 0.36) [12]. In two gout trials, serious adverse events occurred in 2% against 1% on placebo (RR 1.93, 95% CI 0.48 to 7.80) [1]. The frequency was similar between groups in the type 1 diabetes trial [10].
Population
363 adults with chronic kidney disease [9]; 253 people with heart failure [12]; 453 participants in 2 gout trials [1]; 530 people with type 1 diabetes [10].
Sources
[9], [12], [1], [10]
Caveats
None of these trials was large enough to count rare reactions such as severe skin reactions.

Claims tested and not found

  1. That lowering uric acid with allopurinol protects the kidneys. In 363 adults with chronic kidney disease, eGFR fell 3.33 mL/min/1.73 m² a year on allopurinol and 3.23 on placebo [9]. In 530 people with type 1 diabetes, measured GFR after 3 years did not differ from placebo [10].
  2. That allopurinol prevents heart attacks and strokes in people with heart disease. In 5,721 adults with ischemic heart disease and no gout, the cardiovascular outcome occurred in 11.0% on allopurinol and 11.3% on usual care (HR 1.04, 95% CI 0.89 to 1.21) [11].
  3. That allopurinol improves heart failure with high uric acid. In 253 people, clinical status at 24 weeks worsened in 45% on allopurinol and 46% on placebo, and walking distance did not differ [12].

Sources

  1. Seth R, Kydd AS, Buchbinder R, Bombardier C, Edwards CJ. Allopurinol for chronic gout. Cochrane Database of Systematic Reviews. 2014. https://doi.org/10.1002/14651858.CD006077.pub3
  2. Becker MA, Schumacher HR, Wortmann RL, et al. Febuxostat compared with allopurinol in patients with hyperuricemia and gout. New England Journal of Medicine. 2005. https://doi.org/10.1056/NEJMoa050373
  3. Stamp LK, Chapman PT, Barclay ML, et al. A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout. Annals of the Rheumatic Diseases. 2017. https://doi.org/10.1136/annrheumdis-2016-210872
  4. O'Dell JR, Brophy MT, Pillinger MH, et al. Comparative Effectiveness of Allopurinol and Febuxostat in Gout Management. NEJM Evidence. 2022. https://doi.org/10.1056/EVIDoa2100028
  5. Allopurinol tablets, prescribing information. DailyMed, US National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=682dd8b8-fc6e-47c5-95b7-82d7ad96b750
  6. White WB, Saag KG, Becker MA, et al. Cardiovascular Safety of Febuxostat or Allopurinol in Patients with Gout. New England Journal of Medicine. 2018. https://doi.org/10.1056/NEJMoa1710895
  7. Cortes J, Moore JO, Maziarz RT, et al. Control of plasma uric acid in adults at risk for tumor lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone. Results of a multicenter phase III study. Journal of Clinical Oncology. 2010. https://doi.org/10.1200/JCO.2009.26.8896
  8. Ettinger B, Tang A, Citron JT, Livermore B, Williams T. Randomized trial of allopurinol in the prevention of calcium oxalate calculi. New England Journal of Medicine. 1986. https://doi.org/10.1056/NEJM198611273152204
  9. Badve SV, Pascoe EM, Tiku A, et al. Effects of Allopurinol on the Progression of Chronic Kidney Disease. New England Journal of Medicine. 2020. https://doi.org/10.1056/NEJMoa1915833
  10. Doria A, Galecki AT, Spino C, et al. Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes. New England Journal of Medicine. 2020. https://doi.org/10.1056/NEJMoa1916624
  11. Mackenzie IS, Hawkey CJ, Ford I, et al. Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial. The Lancet. 2022. https://doi.org/10.1016/S0140-6736(22)01657-9
  12. Givertz MM, Anstrom KJ, Redfield MM, et al. Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation. 2015. https://doi.org/10.1161/CIRCULATIONAHA.114.014536
  13. Noman A, Ang DS, Ogston S, Lang CC, Struthers AD. Effect of high-dose allopurinol on exercise in patients with chronic stable angina: a randomised, placebo controlled crossover trial. The Lancet. 2010. https://doi.org/10.1016/S0140-6736(10)60391-1
  14. Agarwal V, Hans N, Messerli FH. Effect of allopurinol on blood pressure: a systematic review and meta-analysis. The Journal of Clinical Hypertension. 2013. https://doi.org/10.1111/j.1751-7176.2012.00701.x
  15. Feig DI, Soletsky B, Johnson RJ. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. JAMA. 2008. https://doi.org/10.1001/jama.300.8.924
  16. Yang CY, Chen CH, Deng ST, et al. Allopurinol Use and Risk of Fatal Hypersensitivity Reactions: A Nationwide Population-Based Study in Taiwan. JAMA Internal Medicine. 2015. https://doi.org/10.1001/jamainternmed.2015.3536
  17. Hung SI, Chung WH, Liou LB, et al. HLA-B5801 allele as a genetic marker for severe cutaneous adverse reactions caused by allopurinol. Proceedings of the National Academy of Sciences*. 2005. https://doi.org/10.1073/pnas.0409500102
  18. Somkrua R, Eickman EE, Saokaew S, Lohitnavy M, Chaiyakunapruk N. Association of HLA-B5801 allele and allopurinol-induced Stevens Johnson syndrome and toxic epidermal necrolysis: a systematic review and meta-analysis. BMC Medical Genetics*. 2011. https://doi.org/10.1186/1471-2350-12-118
  19. Stamp LK, Taylor WJ, Jones PB, et al. Starting dose is a risk factor for allopurinol hypersensitivity syndrome: a proposed safe starting dose of allopurinol. Arthritis & Rheumatism. 2012. https://doi.org/10.1002/art.34488

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