Allopurinol

Xanthine oxidase inhibitors

ATC code: M04AA01

Brand names: Zyloprim, Aloprim

Updated 12 Aug 2026 · Methodology

Indications

Gout

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 is usually 300–600 mg/day, and treat-to-target titration may reach 800 mg/day. Start under anti-inflammatory cover (colchicine or an NSAID) to prevent a mobilization flare. In high-risk groups (Han Chinese, Korean, Thai, and African-American patients), HLA-B*5801 testing before initiation is conditionally recommended – positive results raise severe cutaneous reaction risk (DRESS, SJS/TEN) 80-fold; use an alternative (febuxostat).

Sources

ICD-10: M10 · ICD-11: FA25

Prevention of tumor lysis syndrome

First line

Allopurinol is the standard prophylaxis for tumor lysis syndrome in low- and intermediate-risk patients before chemotherapy. It lowers uric acid production but does not break down urate already present, so for high-risk patients (large tumor burden, aggressive lymphomas and leukemias, high baseline urate, renal impairment) rasburicase is preferred. Allopurinol is combined with vigorous hydration, with dose adjustment in reduced kidney function. Based on the Coiffier 2008 guideline and the 2010 TLS expert panel consensus; the indication is on the AEMPS label.

Sources

ICD-10: E88.3 · ICD-11: 5D01

Kidney stone prevention

Adjunct

In patients with frequent kidney stones and high uric acid in blood or urine, allopurinol lowers the recurrence risk. First-line care is high fluid intake and urine alkalinization with citrate (for uric acid stones); allopurinol is added when hyperuricosuria persists. In the Ettinger 1986 RCT, allopurinol reduced recurrence of calcium oxalate stones in hyperuricosuric patients; for uric acid stones the indication is on the AEMPS label and in the EAU guideline. It is an add-on to baseline prevention, not a replacement for fluid intake.

Sources

ICD-10: N20.0 · ICD-11: GB70.0

Marketing claims without evidence base

The drug is promoted for these uses outside international guidelines. Each entry below is analyzed against AEMPS, FDA, EMA, Cochrane and major RCTs.

Asymptomatic hyperuricemia

Not recommended

Per 2020 and 2017, routine urate-lowering therapy in asymptomatic hyperuricemia is not indicated. ACR 2020 conditionally recommends against starting therapy even with concurrent CKD or urolithiasis, and in the CKD-FIX trial allopurinol did not slow CKD progression. Treating an asymptomatic patient carries real harm: severe cutaneous reactions (SJS/TEN, DRESS) and allopurinol hypersensitivity syndrome, more common in HLA-B*5801 carriers. Zero proven benefit against documented harm is why allopurinol is not given routinely here. The widespread practice of prescribing allopurinol 'for high uric acid on labs' without gouty symptoms lacks an evidence base.

Sources

ICD-10: E79.0 · ICD-11: 5C55

Athletic endurance

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, 2017). In sports circles, allopurinol is occasionally promoted to reduce oxidative stress and improve recovery. In athletes without gout, a few studies of prophylactic use do exist (including an RCT in soccer players), but they show no benefit for endurance or performance, only changes in surrogate muscle-damage markers. 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.

Sources

How to read tiers A–F

AStrong evidence – first or second line in international guidelines
BRecommended in selected cases
CStudy data contradict each other
DBenefit not proven, no documented harm
FDocumented harm, or risk without benefit

Mechanism of action

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.

Safety

Contraindications

Hypersensitivity
Severe hepatic impairment
Severe renal impairment (requires dose adjustment)
Acute gout attack at the moment of initiation (start 2 weeks after attack resolution)

Serious adverse effects

Allopurinol hypersensitivity syndrome (DRESS) — severe life-threatening event involving skin, liver, kidneys, and CNS
Stevens-Johnson syndrome, toxic epidermal necrolysis
Hepatotoxicity
Myelosuppression (rare)
Acute interstitial nephritis

Common adverse effects

Skin rash (1–5 % — most mild but warrants reassessment)
Nausea, dyspepsia
Diarrhea
Transient transaminase elevation

Pregnancy: can you take Allopurinol?

AEMPS summary of product characteristics (section 4.6): there is no adequate experience of allopurinol safety in human pregnancy, and animal reproductive toxicity studies have given conflicting results. Allopurinol is used in pregnancy only when there is no safer alternative and the disease itself carries risks for the mother or the fetus.

Breastfeeding: can you take Allopurinol?

Transfers into milk. Per LactMed, use is acceptable with infant monitoring.

Calculate RID Full profile on NIH LactMed ↗

Reference information, not a clinical decision. Discuss feeding pauses or changes with your physician or an IBCLC.

Practical notes

Timing and administration

Take once daily after meals — reduces GI irritation. Start low (100 mg, or 50 mg in reduced eGFR) — abrupt urate lowering early on can precipitate an attack. In the first 3–6 months, give concomitant prophylactic colchicine 0.5–1 mg daily or low-dose NSAIDs alongside allopurinol.

Monitoring

Monitor serum uric acid and eGFR at 2–4 weeks after initiation and each dose change, then every 6 months. With rash, fever, or malaise — immediate discontinuation and medical evaluation: allopurinol hypersensitivity syndrome (DRESS) is a severe, life-threatening event involving skin, liver, kidneys, and brain. Most often within the first 8 weeks of therapy.

Drug–drug interactions

7 pairs found. Sorted from critical to minor.

MajorAzathioprineImmunosuppressants, thiopurines

Mechanism

Azathioprine is converted to 6-mercaptopurine, and xanthine oxidase turns its active metabolites into inactive 6-thiouric acid. Allopurinol blocks xanthine oxidase, so azathioprine and 6-mercaptopurine accumulate. Levels can reach the toxic range with pancytopenia and bone marrow suppression; the Spanish allopurinol SmPC mentions fatal cases. No official label lists the pair as a contraindication: the allopurinol SmPC and the label require a steep cut in the azathioprine dose.

Symptoms

Bone marrow suppression: falling white cells, platelets and haemoglobin, up to pancytopenia. The patient notices sore throat, fever, unexplained bruising or bleeding – the signs the allopurinol SmPC asks patients to report at once.

Management

Avoid the combination where possible, as the allopurinol SmPC requires. If it is clinically necessary, cut the azathioprine dose to a quarter of the usual dose (allopurinol and azathioprine SmPCs; label: 1/3 to 1/4) and check full blood counts often. The azathioprine SmPC already asks for weekly or more frequent counts with platelets during the first 8 weeks of therapy. Febuxostat is not a substitute: it blocks the same enzyme, the FDA contraindicates it with azathioprine and the EU SmPC does not recommend it.

Sources

Pair details →Azathioprine →

MajorCaptoprilACE inhibitor

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.

Sources

Pair details →Captopril →

MajorEnalaprilAngiotensin-converting enzyme inhibitors (ACEi)

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.

Sources

Pair details →Enalapril →

ModerateHydrochlorothiazideThiazide diuretics

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).

Sources

Pair details →Hydrochlorothiazide →

ModerateIndapamideThiazide-like diuretics

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%.

Sources

Pair details →Indapamide →

ModerateWarfarinVitamin K antagonist anticoagulants

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%.

Sources

Pair details →Warfarin →

MinorEtoricoxibSelective COX-2 inhibitor (coxib)

Mechanism

Each occupies a different place in gout treatment: allopurinol lowers urate long term while etoricoxib quells flare inflammation. Neither label names the other substance in its interactions section, and allopurinol reserves its warnings for azathioprine, mercaptopurine and coumarin anticoagulants.

Symptoms

The pair produces no distinct picture. Watch each one separately: skin rash when starting allopurinol, which requires stopping it, and from etoricoxib high blood pressure, oedema and gastric discomfort.

Management

Allopurinol started during a flare can prolong it, which is why it is combined with anti-inflammatory or colchicine cover for the first months. If allopurinol was already being taken before the attack, it is not interrupted: stopping it shifts urate and lengthens the flare. Etoricoxib is withdrawn once inflammation settles.

Sources

Pair details →Etoricoxib →

Label mentions41 mentions

Verbatim lines from the interaction sections, in the language of the label

From this drug’s label

MajorAzathioprine
«6-Mercaptopurina y azatioprina: La azatioprina se metaboliza a 6-mercaptopurina, que se inactiva por acción de la xantina oxidasa. Cuando 6-mercaptopurina o azatioprina se administra por vía oral…»
AEMPS, section 4.5 · Open on CIMA
MajorAzathioprine
«DRUG INTERACTIONS: • The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) • Capecitabine: Avoid concomitant use…»
FDA, section 7 · Open on DailyMed
MajorCapecitabine
«DRUG INTERACTIONS: • The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) • Capecitabine: Avoid concomitant use…»
FDA, section 7 · Open on DailyMed
MajorFluorouracil
«Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets: Intervention Concomitant administration with fluorouracil should be avoided.»
FDA, section 7 · Open on DailyMed
ModerateAmoxicillin
«DRUG INTERACTIONS: • The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) • Capecitabine: Avoid concomitant use…»
FDA, section 7 · Open on DailyMed
Moderateanticoagulantesclass named in the label
«Anticoagulantes cumarínicos: Se han descrito algunos casos de aumento del efecto anticoagulante de warfarina y cumarínicos cuando de administran conjuntamente con alopurinol. Por tanto, todos los…»
AEMPS, section 4.5 · Open on CIMA
Moderateanticoagulantsclass named in the label
«Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets: Intervention Monitor prothrombin time. Adjust the dosage of dicumarol accordingly when allopurinol tablets are…»
FDA, section 7 · Open on DailyMed
ModerateCiclosporin
«Ciclosporina: Algunos informes sugieren que la concentración plasmática de ciclosporina puede aumentar durante el tratamiento concomitante con alopurinol. Se debe considerar la posibilidad de un…»
AEMPS, section 4.5 · Open on CIMA
ModerateTheophylline
«Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets: Intervention Monitor and adjust theophylline doses as reflected in the prescribing information.»
FDA, section 7 · Open on DailyMed
Moderatethiazide diureticsclass named in the label
«DRUG INTERACTIONS: • The following drugs may increase the risk of serious skin reactions: bendamustine, thiazide diuretics, ampicillin and amoxicillin. ( 7.1 ) • Capecitabine: Avoid concomitant use…»
FDA, section 7 · Open on DailyMed
ModerateWarfarin
«Anticoagulantes cumarínicos: Se han descrito algunos casos de aumento del efecto anticoagulante de warfarina y cumarínicos cuando de administran conjuntamente con alopurinol. Por tanto, todos los…»
AEMPS, section 4.5 · Open on CIMA
ModerateWarfarin
«Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets: Intervention Monitor patients on concomitant therapy for excessive anticoagulation. Assess INR frequently and…»
FDA, section 7 · Open on DailyMed
Amoxicillin
«Ampicilina/amoxicilina: Se ha descrito un aumento en la frecuencia de erupción (“rash) cutánea entre los pacientes que reciben ampicilina o amoxicilina concurrentemente con alopurinol en comparación…»
AEMPS, section 4.5 · Open on CIMA
antineoplásicosclass named in the label
«Citostáticos: ciclofosfamida, doxorubicina, bleomicina, procarbazina, mecloretamina»
AEMPS, section 4.5 · Open on CIMA
antineoplasticsclass named in the label
«Drugs Known to Have Clinically Important Drug Interactions with Allopurinol Tablets: Cyclophosphamide and Other Cytotoxic Agents»
FDA, section 7 · Open on DailyMed
Captopril
«Inhibidores de la enzima convertidora de angiotensina (ECA): El riesgo de reacciones cutáneas puede aumentar con la administración concomitante de alopurinol y captopril, especialmente en casos de…»
AEMPS, section 4.5 · Open on CIMA
diuréticosclass named in the label
«Diuréticos: Se ha notificado interacción entre alopurinol y furosemida que resulta en un aumento del urato sérico y de las concentraciones plasmáticas de oxipurinol.»
AEMPS, section 4.5 · Open on CIMA
Furosemide
«Diuréticos: Se ha notificado interacción entre alopurinol y furosemida que resulta en un aumento del urato sérico y de las concentraciones plasmáticas de oxipurinol.»
AEMPS, section 4.5 · Open on CIMA
inhibidores de la ECAclass named in the label
«Inhibidores de la enzima convertidora de angiotensina (ECA): El riesgo de reacciones cutáneas puede aumentar con la administración concomitante de alopurinol y captopril, especialmente en casos de…»
AEMPS, section 4.5 · Open on CIMA
Phenytoin
«Fenitoína: Aunque alopurinol puede inhibir la oxidación hepática de fenitoína, no se ha demostrado su significación clínica.»
AEMPS, section 4.5 · Open on CIMA
Theophylline
«Teofilina: Se ha descrito inhibición del metabolismo de teofilina. El mecanismo de interacción puede explicarse por la xantina oxidasa implicada en la biotransformación de la teofilina en humanos.»
AEMPS, section 4.5 · Open on CIMA
tiazidasclass named in the label
«Diuréticos: Cuando alopurinol se administra con diuréticos, en particular tiazidas, se ha notificado un riesgo mayor de desarrollar reacciones de hipersensibilidad, especialmente en pacientes con…»
AEMPS, section 4.5 · Open on CIMA

From other drugs’ labels

MajorAzathioprine
«El alopurinol, el oxipurinol el tiopurinol y otros inhibidores de la xantina oxidasa tienen un efecto inhibidor sobre el metabolismo de azatioprina mediante el bloqueo de la enzima xantinoxidasa. que…»
AEMPS, section 4.5 · Open on CIMA
MajorAzathioprine
«DRUG INTERACTIONS: Use with xanthine oxidase (XO) inhibitors: One of the pathways for inactivation of azathioprine is inhibited by XO inhibitors (allopurinol or febuxostat). Patients receiving…»
FDA, section 7 · Open on DailyMed
MajorCapecitabine
«DRUG INTERACTIONS: • Allopurinol: Avoid concomitant use of allopurinol with capecitabine. ( 7.1 ) • Leucovorin: Closely monitor for toxicities when capecitabine is coadministered with leucovorin. (…»
FDA, section 7 · Open on DailyMed
ModerateAmoxicillin
«DRUG INTERACTIONS: Co-administration with probenicid is not recommended. ( 7.1 ) Concomitant use of amoxicillin and oral anticoagulants may increase the prolongation of prothrombin time. ( 7.2 )…»
FDA, section 7 · Open on DailyMed
ModerateCaptopril
«Bloqueo dual del sistema renina-angiotensina-aldosterona (SRAA): En pacientes con enfermedad vascular del colágeno (por ejemplo, lupus eritematoso sistémico o esclerodermia) y función renal…»
AEMPS, section 4.4 · Open on CIMA
ModerateChlortalidone
«Alopurinol: Clortalidona puede aumentar las reacciones de hipersensibilidad al alopurinol.»
AEMPS, section 4.5 · Open on CIMA
ModerateEnalapril
«Neutropenia/Agranulocitosis: En pacientes tratados con inhibidores de la ECA se han comunicado casos de neutropenia/agranulocitosis, trombocitopenia y anemia. En pacientes con función renal normal y…»
AEMPS, section 4.4 · Open on CIMA
ModerateHydrochlorothiazide
«Alopurinol: El uso concomitante con diuréticos tiazídicos puede aumentar la incidencia de reacciones de hipersensibilidad a alopurinol.»
AEMPS, section 4.5 · Open on CIMA
ModerateIndapamide
«Alopurinol: El tratamiento concomitante con indapamida puede aumentar la incidencia de reacciones de hipersensibilidad a alopurinol.»
AEMPS, section 4.5 · Open on CIMA
ModerateLisinopril
«Neutropenia/Agranulocitosis: Se ha comunicado neutropenia/agranulocitosis, trombocitopenia y anemia en pacientes que reciben inhibidores de la ECA. En pacientes con función renal normal y sin otras…»
AEMPS, section 4.4 · Open on CIMA
ModerateRamipril
«Alopurinol, inmunosupresores, corticosteroides, procainamida, citostáticos y otras sustancias que puedan alterar el hemograma: Aumento de la probabilidad de reacciones hematológicas (ver sección 4.4).»
AEMPS, section 4.5 · Open on CIMA
Amoxicillin
«Alopurinol: La administración concomitante de alopurinol durante el tratamiento con amoxicilina puede aumentar la probabilidad de reacciones alérgicas cutáneas.»
AEMPS, section 4.5 · Open on CIMA
Ciclosporin
«Fármacos que aumentan los niveles de ciclosporina: Es de esperar que todos los inhibidores del CYP3A4 y/o gp-P aumenten los niveles de ciclosporina. Ejemplos son: nicardipino, metoclopramida…»
AEMPS, section 4.5 · Open on CIMA
Famciclovir
«Potential for Other Drugs to Affect Penciclovir: No clinically significant alterations in penciclovir pharmacokinetics were observed following single-dose administration of 500 mg famciclovir after…»
FDA, section 7 · Open on DailyMed
Glimepiride
«alopurinol, probenecid, sulfinpirazona,»
AEMPS, section 4.5 · Open on CIMA
Theophylline
«alopurinol, febuxostat,»
AEMPS, section 4.5 · Open on CIMA
Theophylline
«Drug Interactions:: Allopurinol Decreases theophylline clearance at allopurinol doses ≥600 mg/day. 25% increase»
FDA, section 7 · Open on DailyMed
Warfarin
«Inhibidores enzimáticos: pueden potenciar el efecto anticoagulante, con riesgo de hemorragias, debido a una inhibición de su metabolismo hepático, cuando se administra conjuntamente con: alopurinol…»
AEMPS, section 4.5 · Open on CIMA

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Frequently asked

What is Allopurinol used for?

Allopurinol is evaluated for the following indications with varying evidence strength: Gout (evidence tier A), Prevention of tumor lysis syndrome (evidence tier A), Kidney stone prevention (evidence tier B). See the full indication matrix with dosing and citations above on this page.

What are the side effects of Allopurinol?

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.

Is Allopurinol safe during pregnancy?

Is Allopurinol compatible with breastfeeding?

Transfers into milk. Per LactMed, use is acceptable with infant monitoring.

Who should not take Allopurinol?

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.

Official sources

Direct links to regulator labels. Open in a new tab.

AEMPS / CIMA
FDA / DailyMedLabel dated 08/27/2026
GRLSLabel dated 07/02/2025

Other drugs in this group

Colchicine, Febuxostat