Allopurinol: Uses, Dosage & Side Effects
Xanthine oxidase inhibitor for gout prevention and uric acid reduction
📊 Quick facts about Allopurinol
💡 Key takeaways about Allopurinol
- First-line urate-lowering therapy: Allopurinol is the recommended first-choice treatment for lowering uric acid in gout, supported by ACR 2020 and EULAR 2022 guidelines
- Start low, go slow: Treatment should begin at 100 mg daily (or less in renal impairment) and be gradually increased every 2–4 weeks until the target uric acid level below 360 μmol/L (6 mg/dL) is achieved
- Do not start during an acute attack: Initiating allopurinol during a gout flare can worsen symptoms – wait until the attack has fully resolved before starting treatment
- Serious skin reactions are rare but important: Stop allopurinol immediately and seek emergency care if you develop any rash, fever, or mouth sores, as these may indicate Stevens-Johnson syndrome or allopurinol hypersensitivity syndrome
- Lifelong treatment is usually necessary: Allopurinol works only while you take it – stopping treatment allows uric acid levels to rise again and gout attacks to return
What Is Allopurinol and What Is It Used For?
Allopurinol is an oral xanthine oxidase inhibitor that lowers uric acid levels in the blood. It is the most commonly prescribed medication for preventing gout attacks and is also used to treat kidney stones caused by uric acid, to prevent tumour lysis syndrome during cancer chemotherapy, and to manage rare enzyme disorders such as Lesch-Nyhan syndrome.
Allopurinol belongs to a class of medications known as xanthine oxidase inhibitors. It works by blocking xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid (urate). By inhibiting this enzyme, allopurinol and its active metabolite oxypurinol reduce the production of uric acid throughout the body. This decrease in uric acid production leads to lower concentrations in the blood (serum urate) and in the urine, which in turn prevents the formation and deposition of monosodium urate crystals in joints, soft tissues, and the urinary tract.
Gout is a form of inflammatory arthritis caused by the deposition of monosodium urate crystals in and around joints. It affects approximately 1–4% of the adult population worldwide, making it the most common form of inflammatory arthritis in men and postmenopausal women. Allopurinol has been the mainstay of urate-lowering therapy since its introduction in the 1960s and remains the first-line treatment recommended by all major international rheumatology guidelines, including the ACR (2020) and EULAR (2022).
Beyond gout, allopurinol is indicated for the management of hyperuricaemia (elevated uric acid levels) associated with several clinical conditions. In patients undergoing chemotherapy or radiation therapy for haematological malignancies, rapid tumour cell destruction can release large amounts of purines, leading to a dangerous surge in uric acid known as tumour lysis syndrome. Allopurinol is routinely given prophylactically before and during cancer treatment to prevent this potentially life-threatening complication, which can cause acute kidney injury from uric acid crystallisation in the renal tubules.
Allopurinol is also used in the prevention and treatment of uric acid kidney stones (nephrolithiasis) and in patients with recurrent calcium oxalate stones associated with hyperuricosuria. Additionally, it is the treatment of choice for certain rare inherited enzyme disorders, most notably Lesch-Nyhan syndrome, a condition characterised by massive overproduction of uric acid due to deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT).
How does allopurinol work?
Allopurinol is a structural analogue of hypoxanthine. After oral administration, it is rapidly absorbed from the gastrointestinal tract and converted by xanthine oxidase itself into its primary active metabolite, oxypurinol (also known as alloxanthine). Both allopurinol and oxypurinol inhibit xanthine oxidase, but oxypurinol is the principal mediator of the drug's therapeutic effect because of its much longer half-life (18–30 hours, compared with only 1–2 hours for allopurinol). This sustained inhibition means that a single daily dose is sufficient to provide continuous uric acid lowering.
By reducing uric acid production, allopurinol shifts the balance from supersaturation (where urate crystals form) to undersaturation (where existing crystals gradually dissolve). Over months to years of consistent treatment, the urate crystal deposits (tophi) that accumulate in joints and soft tissues slowly shrink and may eventually disappear completely. This crystal dissolution is the fundamental goal of urate-lowering therapy and is the reason that allopurinol treatment is typically lifelong.
What Should You Know Before Taking Allopurinol?
Before starting allopurinol, inform your doctor about any kidney or liver disease, current gout attacks, and all medications you are taking. Certain populations (Han Chinese, Thai, Korean ancestry) should be tested for HLA-B*5801 before starting treatment due to increased risk of severe hypersensitivity reactions.
Contraindications
Allopurinol should not be taken by anyone with a known allergy (hypersensitivity) to allopurinol or any of the inactive ingredients in the tablets. If you have previously experienced a hypersensitivity reaction to allopurinol, you must not take it again, as re-exposure can trigger an even more severe reaction. There are no other absolute contraindications, but several conditions require special caution and close medical supervision.
Warnings and precautions
Before starting allopurinol, discuss the following with your doctor:
- Kidney disease: Allopurinol and its metabolite oxypurinol are primarily excreted by the kidneys. Impaired kidney function leads to higher drug levels and an increased risk of side effects, including hypersensitivity syndrome. Your doctor will adjust the dose based on your kidney function (creatinine clearance or eGFR).
- Liver disease: Liver function tests should be monitored periodically during treatment, as allopurinol can rarely cause hepatitis or elevated liver enzymes.
- Current gout attack: Do not start allopurinol during an acute gout flare. Treatment should be initiated at least 2–4 weeks after the acute episode has fully resolved to avoid prolonging or worsening the attack.
- HLA-B*5801 testing: The HLA-B*5801 allele is strongly associated with the risk of severe allopurinol hypersensitivity reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This allele is significantly more prevalent in individuals of Han Chinese, Thai, or Korean descent (prevalence 6–8%), as well as in African Americans (3.8%). The ACR and EULAR guidelines recommend HLA-B*5801 testing before starting allopurinol in these populations. Patients who test positive should not be prescribed allopurinol.
- Thyroid disorders: Long-term allopurinol use has been associated with elevated thyroid-stimulating hormone (TSH) levels. Thyroid function should be monitored in patients with pre-existing thyroid conditions.
- Cardiovascular medication: Patients taking diuretics (water tablets) and/or ACE inhibitors may be at increased risk of allopurinol hypersensitivity. Extra caution and close monitoring are required.
Allopurinol hypersensitivity syndrome (AHS) is a rare but potentially life-threatening reaction. Early signs include fever, skin rash, mouth ulcers, sore throat, and general malaise. Stop taking allopurinol immediately and seek emergency medical attention if you develop any rash or these symptoms. The reaction can progress to Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), characterised by widespread blistering and peeling of the skin. Risk factors include renal impairment, diuretic use, and carrying the HLA-B*5801 allele.
Pregnancy and breastfeeding
Allopurinol is not recommended during pregnancy unless clearly necessary and the potential benefit outweighs the risk. There is insufficient data on the safety of allopurinol in human pregnancy, and animal studies have shown potential reproductive toxicity at high doses. Women of childbearing potential should discuss contraception with their doctor before starting treatment.
Allopurinol and its active metabolite oxypurinol are excreted in breast milk. Although the concentrations are generally low, the manufacturer advises against breastfeeding while taking allopurinol due to insufficient safety data in nursing infants. If allopurinol treatment is essential, the decision to discontinue breastfeeding or discontinue the drug should be made in consultation with your doctor, taking into account the importance of the medication to the mother.
Driving and operating machinery
Allopurinol may occasionally cause drowsiness, dizziness, or impaired coordination. If you experience any of these effects, do not drive or operate machinery until you know how the medication affects you. These effects are uncommon but may be more pronounced when starting treatment or adjusting the dose.
Use in children
Allopurinol use in children is rarely indicated except in specific circumstances: management of hyperuricaemia associated with malignancies (particularly leukaemia) during chemotherapy, and treatment of certain inherited enzyme disorders such as Lesch-Nyhan syndrome. In these cases, the dose is calculated based on body weight (10–20 mg/kg/day, up to a maximum of 400 mg daily), divided into up to three doses. The use of allopurinol in children should be under specialist supervision.
How Does Allopurinol Interact with Other Drugs?
Allopurinol has clinically significant interactions with several important medications, including azathioprine, 6-mercaptopurine, warfarin, theophylline, and certain antibiotics. Always inform your doctor and pharmacist about all medications, supplements, and herbal products you are taking before starting allopurinol.
Because allopurinol inhibits xanthine oxidase, it can profoundly affect the metabolism of drugs that are broken down by this enzyme. Additionally, the drug can influence the pharmacokinetics and pharmacodynamics of several other medication classes through different mechanisms. Understanding these interactions is critical for safe prescribing and for patients to recognise when to alert their healthcare provider.
Major interactions
| Interacting Drug | Effect | Clinical Action |
|---|---|---|
| Azathioprine | Allopurinol inhibits the metabolism of azathioprine via xanthine oxidase, causing dangerously elevated drug levels and severe bone marrow suppression (pancytopenia) | Reduce azathioprine dose by 50–75% if co-administration is unavoidable. Regular blood count monitoring essential |
| 6-Mercaptopurine | Same mechanism as azathioprine – markedly increased drug levels leading to severe myelosuppression | Reduce 6-mercaptopurine dose by 50–75%. Frequent blood count monitoring required |
| Ciclosporin (cyclosporine) | Allopurinol may increase ciclosporin blood levels, increasing risk of nephrotoxicity | Monitor ciclosporin levels closely and adjust dose as needed |
| Didanosine | Allopurinol increases didanosine levels, raising risk of toxicity | Combination generally not recommended. If necessary, reduce didanosine dose and monitor closely |
Moderate interactions
| Interacting Drug | Effect | Clinical Action |
|---|---|---|
| Warfarin | Allopurinol may enhance the anticoagulant effect of warfarin by inhibiting its hepatic metabolism | Monitor INR more frequently when starting or changing allopurinol dose. Warfarin dose may need reduction |
| Phenytoin | Allopurinol may increase phenytoin levels by inhibiting hepatic metabolism | Monitor phenytoin levels and clinical response. Adjust dose as needed |
| Theophylline | Allopurinol inhibits theophylline metabolism, increasing plasma levels especially at doses above 600 mg/day | Monitor theophylline levels. Dose adjustment may be required |
| Ampicillin / Amoxicillin | Significantly increased incidence of skin rash when used with allopurinol (up to 20% versus 2–3% with the antibiotic alone) | Consider alternative antibiotics if possible. Monitor closely for rash if used together |
| ACE inhibitors + diuretics | Increased risk of allopurinol hypersensitivity reactions, particularly in patients with renal impairment | Use with caution. Start at a low dose and monitor renal function and for signs of hypersensitivity |
| Chlorpropamide | Allopurinol may prolong the hypoglycaemic effect of chlorpropamide, increasing risk of low blood sugar | Monitor blood glucose more frequently. Chlorpropamide dose may need adjustment |
| Aluminium hydroxide | May reduce the absorption and efficacy of allopurinol | Separate administration by at least 3 hours |
Other notable interactions
When allopurinol is used alongside cytotoxic chemotherapy agents (such as cyclophosphamide, doxorubicin, bleomycin, procarbazine, and alkylating agents), there is an increased risk of blood dyscrasias (abnormal blood cell counts) compared to when these agents are used alone. Regular full blood count monitoring should be performed at closer intervals in patients receiving both allopurinol and cytotoxic drugs.
Probenecid and high-dose salicylates (aspirin) may increase the excretion of oxypurinol, the active metabolite of allopurinol, potentially reducing its effectiveness. If these medications are used together, the allopurinol dose may need to be adjusted and serum uric acid levels should be monitored more frequently to ensure adequate urate lowering.
If you notice unexplained bruising, bleeding, persistent sore throat, or fever while taking allopurinol – especially if you are also taking azathioprine, 6-mercaptopurine, or cytotoxic drugs – seek medical attention immediately. These symptoms may indicate a serious blood disorder that requires urgent investigation.
What Is the Correct Dosage of Allopurinol?
Allopurinol is usually started at 100 mg once daily and gradually increased every 2–4 weeks until the target serum uric acid level is reached. The usual maintenance dose is 200–300 mg daily for mild gout, but doses up to 800–900 mg daily may be needed in severe cases. Dose reduction is essential in patients with kidney disease.
The dosage of allopurinol is highly individual and should be determined by your doctor based on your serum uric acid levels, kidney function, and clinical response. The fundamental principle of allopurinol dosing is “start low, go slow” – beginning at a low dose and gradually titrating upward to minimise the risk of triggering gout flares and hypersensitivity reactions.
Adults
Standard dosing for gout and hyperuricaemia
- Starting dose: 100 mg once daily, taken after a meal
- Dose titration: Increase by 100 mg every 2–4 weeks, guided by serum uric acid levels
- Usual maintenance dose: 200–300 mg daily for mild to moderate cases
- Maximum dose: Up to 800–900 mg daily in severe cases (divided into 2–3 doses if above 300 mg)
- Target serum urate: Below 360 μmol/L (6 mg/dL); below 300 μmol/L (5 mg/dL) for patients with tophi (ACR 2020)
The tablet should be taken after a meal with a full glass of water to reduce gastrointestinal side effects. If the total daily dose exceeds 300 mg, it is generally better to divide it into two or three equal doses taken throughout the day, as this reduces the risk of nausea and other gastrointestinal discomfort. Adequate fluid intake (at least 2 litres per day) is recommended to promote dilute urine and reduce the risk of uric acid stone formation, particularly during the initial weeks of treatment.
Dose adjustment in renal impairment
Renal dosing guidelines
- eGFR 30–60 mL/min: Start at 50–100 mg daily. Maximum usually 200–300 mg daily
- eGFR 15–30 mL/min: Start at 50 mg daily or 100 mg every other day. Maximum usually 100–200 mg daily
- eGFR <15 mL/min or dialysis: 100 mg every 2–3 days, or 300–400 mg immediately after each dialysis session (2–3 times per week)
Note: Current ACR and EULAR guidelines support cautious dose escalation above traditional creatinine clearance-based limits, provided the patient is monitored carefully and tolerates the dose well. The goal remains achieving the serum urate target.
Elderly
There is no specific dose recommendation solely based on age. However, older patients are more likely to have reduced kidney function and to be taking diuretics or ACE inhibitors, all of which increase the risk of adverse effects. Therefore, the starting dose should be at the lower end (50–100 mg daily) and titration should be slower and more cautious. Kidney function should be checked before starting and regularly during treatment.
Children and adolescents
Paediatric dosing (under 15 years)
- Dose: 10–20 mg/kg body weight per day
- Maximum: 400 mg daily
- Administration: Divided into up to three doses daily
- Indications: Primarily for malignancies (especially leukaemia) and enzyme disorders (Lesch-Nyhan syndrome)
Missed dose
If you forget to take a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a missed one. Missing a single dose is unlikely to cause a gout flare, but consistent daily use is important for long-term uric acid control.
Overdose
In the event of an overdose, seek medical attention immediately or contact your local poison control centre. Symptoms of allopurinol overdose may include nausea, vomiting, diarrhoea, and dizziness. Treatment is supportive and symptomatic. Because both allopurinol and oxypurinol are dialysable, haemodialysis may be considered in severe cases, although data on its clinical benefit in overdose are limited.
It is important to continue taking allopurinol as prescribed by your doctor, even if you feel well and are not experiencing gout attacks. Stopping treatment will allow uric acid levels to rise again, often leading to a return of gout flares. If you need to stop for any reason (e.g. due to side effects), your doctor will advise you on how to manage this safely.
What Are the Side Effects of Allopurinol?
The most common side effect of allopurinol is skin rash, which occurs in approximately 2–3% of patients. Rare but serious side effects include allopurinol hypersensitivity syndrome, Stevens-Johnson syndrome, and toxic epidermal necrolysis. If you develop any rash, fever, or mouth sores, stop taking allopurinol immediately and seek medical attention.
Like all medications, allopurinol can cause side effects, although not everyone will experience them. Most side effects are mild and transient, particularly gastrointestinal symptoms that tend to improve as the body adjusts to the medication. However, some side effects can be serious and require immediate medical attention. The frequency categories below are based on standard medical reporting conventions.
Common
- Skin rash (ranging from mild to moderate)
- Elevated thyroid-stimulating hormone (TSH) levels
Uncommon
- Nausea or vomiting
- Diarrhoea
- Abnormal liver function tests
- Hypersensitivity reactions with skin peeling, blisters, or mouth ulcers
Rare
- Hepatitis (liver inflammation)
- Fever, chills, headache, and muscle pain (flu-like symptoms)
- Severe multi-organ hypersensitivity reaction with fever, rash, joint pain, and abnormal blood and liver values
- Bleeding on lips, eyes, mouth, nose, or genitals
- Stevens-Johnson syndrome (SJS) – blistering skin reaction with mucous membrane involvement
Very Rare
- Severe allergic reaction (anaphylaxis) with facial or throat swelling
- Toxic epidermal necrolysis (TEN) – widespread skin loss
- Blood disorders: agranulocytosis, aplastic anaemia, thrombocytopenia
- Blood in urine (haematuria)
- High blood cholesterol (hyperlipidaemia)
- Peripheral neuropathy (numbness, tingling, weakness in extremities)
- Headache, dizziness, drowsiness, visual disturbances
- Chest pain (angina), high blood pressure, slow heartbeat
- Oedema (fluid retention, particularly ankle swelling)
- Altered glucose metabolism (diabetes)
- Depression, taste changes, hair loss or discolouration
- Cataracts
- Male infertility, erectile dysfunction
- Breast enlargement (gynaecomastia) in both men and women
Frequency not known (cannot be estimated from available data):
- Aseptic meningitis: Inflammation of the membranes surrounding the brain and spinal cord, with symptoms including neck stiffness, headache, nausea, fever, or altered consciousness. Seek immediate medical attention if these symptoms occur.
- Lichenoid skin eruptions: Itchy red-purple skin patches and/or thread-like white-grey lines on mucous membranes.
Stop taking allopurinol and seek immediate medical care if you experience: any skin rash or skin changes (no matter how mild), mouth or genital sores, fever with rash, difficulty breathing, swelling of face or throat, severe blistering or peeling skin, unexplained bruising or bleeding, persistent sore throat or signs of infection. Early recognition and prompt discontinuation of allopurinol are critical for the best outcome in hypersensitivity reactions.
Gout flares during early treatment
It is important to be aware that gout attacks may actually increase in frequency during the first weeks to months after starting allopurinol. This is a well-recognised phenomenon caused by the mobilisation and dissolution of urate crystal deposits as serum uric acid levels fall. As existing crystals shrink and shed from tissues, they can trigger inflammation in the joints. This does not mean the treatment is not working – on the contrary, it is a sign that urate crystals are being dissolved. To prevent these flares, your doctor will usually prescribe prophylactic treatment with low-dose colchicine (typically 0.5 mg once or twice daily) or a low-dose NSAID for the first 3–6 months of allopurinol therapy.
Effects on blood
Allopurinol can occasionally affect the blood, which may manifest as easy bruising, sore throat, or other signs of infection. These effects are more common in patients with existing liver or kidney problems. If you notice any of these symptoms, contact your doctor as soon as possible for a blood test. Regular blood monitoring is particularly important for patients taking allopurinol alongside cytotoxic drugs, immunosuppressants, or in those with impaired renal or hepatic function.
How Should You Store Allopurinol?
Store allopurinol tablets at room temperature below 30°C (86°F) in the original packaging. Keep out of reach of children and do not use after the expiry date printed on the packaging.
Allopurinol tablets should be stored at a temperature not exceeding 30°C (86°F). Keep the tablets in their original blister packaging to protect them from moisture and light. Do not transfer the tablets to other containers unless specifically designed for medication storage. As with all medications, keep allopurinol out of the sight and reach of children.
Do not use allopurinol tablets after the expiry date printed on the blister pack and the outer carton. The expiry date refers to the last day of the stated month. Do not dispose of medications by flushing them down the toilet or throwing them in household waste. Return unused or expired tablets to your pharmacy for safe disposal in accordance with local regulations. This helps protect the environment.
What Does Allopurinol Contain?
Allopurinol tablets contain the active substance allopurinol in strengths of 100 mg and 300 mg. The inactive ingredients include lactose monohydrate, crospovidone, maize starch, povidone K30, and magnesium stearate.
Active ingredient
The active substance is allopurinol. Each tablet contains either 100 mg or 300 mg of allopurinol, depending on the prescribed strength. Allopurinol is a white to off-white crystalline powder that acts as a xanthine oxidase inhibitor.
Inactive ingredients (excipients)
The other ingredients in the tablets are:
- Lactose monohydrate: A sugar used as a filler and binder. Patients with lactose intolerance should discuss this with their doctor before taking the tablets.
- Crospovidone (type B): A disintegrant that helps the tablet break apart in the stomach for absorption.
- Maize starch: Used as a filler and binder.
- Povidone K30: A binding agent that holds the tablet together.
- Magnesium stearate: A lubricant used in tablet manufacturing to prevent sticking.
Tablet appearance
Allopurinol 100 mg tablets are white to off-white, round, biconvex, uncoated tablets. Allopurinol 300 mg tablets are white to off-white, round, biconvex, uncoated tablets with a bevelled edge. The tablets are supplied in PVC/aluminium blister packs.
Frequently Asked Questions About Allopurinol
References
- FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology Guideline for Management of Gout. Arthritis Care Res (Hoboken). 2020;72(6):744–760. doi:10.1002/art.41247
- Richette P, Doherty M, Pascual E, et al. 2022 updated EULAR evidence-based recommendations for the management of gout. Ann Rheum Dis. 2023;82(1):3–14. doi:10.1136/ard-2022-223645
- Hui M, Carr A, Cameron S, et al. The British Society for Rheumatology Guideline for the Management of Gout. Rheumatology (Oxford). 2017;56(7):e1–e20. doi:10.1093/rheumatology/kex156
- World Health Organization. WHO Model List of Essential Medicines – 23rd List (2023). Geneva: WHO; 2023.
- British National Formulary (BNF). Allopurinol. National Institute for Health and Care Excellence (NICE). Accessed January 2026.
- European Medicines Agency (EMA). Allopurinol – Summary of Product Characteristics. EMA. Accessed January 2026.
- 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 Rheum. 2012;64(8):2529–2536. doi:10.1002/art.34488
- Hershfield MS, Callaghan JT, Tassaneeyakul W, et al. Clinical Pharmacogenetics Implementation Consortium Guidelines for Human Leukocyte Antigen-B Genotype and Allopurinol Dosing. Clin Pharmacol Ther. 2013;93(2):153–158. doi:10.1038/clpt.2012.209
- Stamp LK, Chapman PT, Barclay M, et al. How to dose allopurinol in renal impairment: a revised dose-escalation strategy. Semin Arthritis Rheum. 2022;55:152026.
- Dalbeth N, Merriman TR, Stamp LK. Gout. Lancet. 2016;388(10055):2039–2052. doi:10.1016/S0140-6736(16)00346-9
Editorial Team
iMedic Medical Editorial Team – Specialists in clinical pharmacology, rheumatology, and internal medicine with extensive experience in gout management and pharmacotherapy.
Independently reviewed by the iMedic Medical Review Board to ensure accuracy, completeness, and adherence to evidence-based medicine standards (GRADE framework, Level 1A evidence).
All content follows international medical guidelines including ACR, EULAR, BSR, WHO, EMA, FDA, and BNF. We maintain complete independence with no pharmaceutical company sponsorship, funding, or advertising. Content is reviewed and updated at least annually. Read our full editorial policy.