Focus on Allopurinol

Open AccessFocus on Allopurinol S Davis S Davis1 Affiliations 1Amayeza Info Services Published Online:1 Sep 2025https://doi.org/10.36303/SAPJ.3193https://hdl.handle.net/10520/ejc-mp_sapj_v92_n4_a8SectionsPDFAbstract ToolsAdd to favouritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditGMailOutlookCopy LinkMendeley AboutAbstractUrate saturation of extracellular fluids results in hyperuricaemia.1 The deposition of this monosodium urate (MSU) in joints, soft tissues and bones, triggers an inflammatory arthritis and can manifest in many forms including acute gout flare, chronic gouty arthritis and tophaceous gout (formation of tophi).1 Factors that lead to changes in the extracellular urate concentration have the potential to trigger a gout flare-up and include stress (mainly due to medical conditions), dietary choices and drugs, including aspirin, diuretics and even allopurinol.IntroductionUrate saturation of extracellular fluids results in hyperuricaemia.1 The deposition of this monosodium urate (MSU) in joints, soft tissues and bones, triggers an inflammatory arthritis and can manifest in many forms including acute gout flare, chronic gouty arthritis and tophaceous gout (formation of tophi).1 Factors that lead to changes in the extracellular urate concentration have the potential to trigger a gout flare-up and include stress (mainly due to medical conditions), dietary choices and drugs, including aspirin, diuretics and even allopurinol.IndicationsAllopurinol is used to reduce urate concentrations in body fluids and/or urine to prevent or reverse the deposition of urate/uric acid and is indicated in the management of the main clinical manifestations of urate deposition which include chronic gouty arthritis, idiopathic gout and skin tophi.2Mechanism of actionAllopurinol, and its active metabolite oxypurinol, both inhibit xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid, thus decreasing the production of uric acid.3 By lowering both serum and urine concentrations of uric acid below its solubility limits, allopurinol prevents or decreases urate deposition in the joints, thereby preventing the occurrence or progression of gouty arthritis.4PharmacokineticsAround 80 to 90% of allopurinol is absorbed from the gastrointestinal tract following oral administration.4 Seventy percent of allopurinol is metabolised in the liver and converted to oxypurinol by oxidative metabolism.4 The half-life of allopurinol is one to three hours and for oxypurinol the half-life is around 15 hours (12–30 hours), and is prolonged in patients with impaired kidney function.3,5 Oxypurinol, and up to 10% of unchanged allopurinol, is excreted in the urine.5Dosing (adults)Allopurinol treatment should be introduced at a low dosage of 100 mg/day to reduce the risk of adverse reactions such as nausea, vomiting and diarrhoea.2 If needed, the dose may be increased by 100 mg/day every two to five weeks until the target serum uric acid level is achieved.3 The usual maintenance dose is 300 mg/day. However, doses of up to 900 mg/day have been used.2It is recommended that allopurinol be taken after meals for better gastrointestinal tolerability.2,6Renal impairmentAllopurinol is excreted in the kidney and reduced renal function may lead to accumulation of the medicine and its metabolites. The dose and the frequency of dosing may therefore require reduction in these patients. The following schedule is recommended as guidance in adult patients with impaired renal function:2Creatinine clearance > 20 ml/minutegive standard doseCreatinine clearance between 10 and 20 ml/minutegive 100 to 200 mg/dayCreatinine clearance < 10 ml/minutegive 100 mg/day or at longer intervals.If plasma monitoring facilities are available, plasma oxypurinol levels should be maintained below 100 micromol/litre (15,2 micrograms/mL).2Allopurinol and its metabolites are removed by renal dialysis and dosages should be adjusted accordingly.2Hepatic impairmentReduced doses should be used in patients with hepatic impairment. Periodic liver function tests are recommended during the early stages of therapy.2EfficacyA 2014 Cochrane review reported that allopurinol 300 mg daily increases the proportion of patients achieving a target serum urate concentration (25/26 patients achieved target serum urate concentrations with allopurinol 300 mg daily compared to 0/26 with placebo).7 A summary of two Cochrane reviews in 2014, concluded that there is moderate quality data supporting the efficacy and safety of allopurinol in gout.8 Significantly more (38%) participants taking allopurinol, achieved a serum urate level of < 6.0 mg/dl when compared to placebo.8SafetyContraindicationsAllopurinol is contraindicated in patients with hypersensitivity to allopurinol or any excipients in the product, in patients with severe hepatic or renal disorders and in patients with an acute gout attack.2Special warnings and precautionsAllopurinol should not be started until an acute attack of gout has completely subsided as further attacks may be precipitated by allopurinol.2 Due to the destabilisation of intra-articular uric acid microtophi when initiating any urate-lowering therapy, there is an increased incidence of acute gouty flares, especially during the initial few months of allopurinol therapy.3 Thus it is advisable to give a nonsteroidal anti-inflammatory drug (NSAID) or colchicine for at least one month when starting treatment with allopurinol.2,6 If acute attacks occur in patients receiving allopurinol, treatment with allopurinol should continue at the same dose while the acute attack is treated with a NSAID or colchicine.2If a skin rash or other signs of hypersensitivity occur, treatment with allopurinol should be withdrawn immediately as this could result in more serious hypersensitivity reactions including Stevens-Johnsons syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS). After recovery from mild symptoms, allopurinol may be reintroduced at a low dose (e.g. 50 mg per day) and gradually increased. If the rash recurs, allopurinol should be permanently withdrawn.2Certain populations (including people of Han Chinese, African and Indian ancestry) carry the HLAB-B*5801 allele which is considered a genetic risk factor for serious hypersensitivity reactions (e.g. SJS/TEN) with allopurinol use. Screening of these high-risk patients should be considered before starting treatment with allopurinol. Those individuals who test positive should not start treatment with allopurinol unless there are no other reasonable therapeutic options and the benefits of use outweigh the potential associated risk. Those who test negative may still be at risk of SJS/TEN.2Drug interactionsAllopurinol may increase the activity of certain medications. When using 6-mercaptopurine or azathioprine with allopurinol, the dose of 6-mercaptopurine or azathioprine should be reduced to a quarter of the usual dose.2,6 Theophylline metabolism may be inhibited, and theophylline levels should be monitored in patients starting or increasing allopurinol therapy. Plasma concentration of ciclosporin may be increased and ciclosporin toxicity should be considered if used with allopurinol.Medicines with uricosuric activity such as probenecid or large doses of salicylate may accelerate the excretion of oxypurinol which may reduce the efficacy of allopurinol.6Concomitant use of allopurinol and ampicillin or amoxicillin may increase the risk of developing a skin rash. When possible, an alternative to ampicillin or amoxicillin should be considered in patients using allopurinol.6Please refer to the manufacturer's professional information for further information on possible drug-drug interactions.Adverse effectsThe most common adverse effects associated with the use of allopurinol include maculopapular pruritic rash, nausea and vomiting.3 Gastrointestinal side effects can be reduced by taking allopurinol with plenty of liquids and by having frequent small meals.9 Other adverse effects include altered taste, drowsiness and diarrhoea.Less commonly, allopurinol can cause a rash or flaking of the skin. Patients should stop treatment if a rash develops, especially if it is a severe skin rash or, in rare instances, if mouth ulceration occurs.9 Other less common and rare side-effects include liver necrosis, granulomatous hepatitis, cholestatic jaundice, interstitial nephritis, and vasculitis.Important prescribing pointsAllopurinol should not be initiated until an acute attack of gout has completely subsided. There is an increased incidence of acute gouty flares, especially during the initial few months when starting treatment.3 Thus, it is advisable to give an NSAID or colchicine concurrently with allopurinol for at least one to six months when starting treatment.2,9A high fluid intake and frequent small meals may reduce the incidence of nausea and vomiting associated with allopurinol therapy.9Patients should be warned that drowsiness, vertigo and ataxia may occur and should exercise caution when driving, using machinery or participating in dangerous activities.5,6A doctor should be consulted if a skin rash or any other sign of hypersensitivity occurs.2,51. Afzal MRednam MGujarathi RWidrich J "Gout" StatPearlsAvailable from: https://www.ncbi.nlm.nih.gov/books/NBK546606/Accessed 7 July 2025 Google Scholar2. Zyloprim® (allopurinol) Package Insert Pharmacare LimitedWoodmeadSouth Africa15Feb2022 Google Scholar3. Qurie APreuss CVMusa R "Allopurinol" StatPearlsAvailable from: https://www.ncbi.nlm.nih.gov/books/NBK499942/Accessed 1 July 2025 Google Scholar4. AllopurinolIn Depth Answers [database on the Internet]Greenwood Village (CO)IBM Corporation2025[cited 2 July 2025]. Available from: www.micromedexsolutions.com. Subscription required to view Google Scholar5. Rossiter DSouth African Medicines Formulary (SAMF) [online]Health and Medical Publishing Group of the South African Medical AssociationCape Town, South Africa Google Scholar6. Adco Allopurinol 300 TabletsPackage insert Adcock Ingram LimitedMidrand, South Africa26November2024 Google Scholar7. Seth RKydd ASBuchbinder RBombardier CEdwards CJ "Allopurinol for chronic gout" Cochrane Database of Systematic Reviews2014 DOI: https://doi.org/10.1002/14651858.CD006077.pub3 Google Scholar8. Kydd ASSeth RBuchbinder Ret al. "Urate-lowering therapy for the management of gout: a summary of 2 Cochrane reviews" Journal of Rheumatology Supplement2014 923341 DOI: https://doi.org/10.3899/jrheum.140460 Google Scholar9. Finch AKubler P "The management of gout" Australian Prescriber2016 394119 DOI: https://doi.org/10.18773/austprescr.2016.047 Google Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 92, Issue 4 | Sep 2025 LanguagesEnglish InformationCopyright © 2025, Medpharm Publications:All rights reservedLicensesPDF download Disclosure The authors confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship but are not listed. The authors confirm that they have given due consideration to the protection of intellectual property associated with this work and that there are no impediments to publication, including the timing of publication, with respect to intellectual property. Ethical conduct of research The authors state that they have obtained appropriate institutional review board outlined in the Declaration of Helsinki for all human or animal experimental investigations. A signed informed consent document has been obtained from all participants included in the study.