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Allopurinol V.1.svg
Allopurinol 3d structure.png
Systematic (IUPAC) name
Clinical data
Trade names Zyloprim
AHFS/ monograph
MedlinePlus a682673
  • C(USA)
Legal status
Routes of
tablet (100, 300 mg)
Pharmacokinetic data
Bioavailability 78±20%
Protein binding Negligible
Metabolism hepatic (80% oxypurinol, 10% allopurinol ribosides)
Biological half-life 2 h (oxypurinol 18-30 h)
CAS Number 315-30-0 YesY
ATC code M04AA01
PubChem CID: 2094
DrugBank DB00437 YesY
ChemSpider 2010 YesY
KEGG D00224 YesY
ChEBI CHEBI:40279 YesY
Chemical data
Formula C5H4N4O
Molecular mass 136.112 g/mol
 YesY (what is this?)  (verify)

Allopurinol, sold under the brand name Zyloprim and generics, is a medication used primarily to treat excess uric acid in the blood and its complications, including chronic gout.[1] It is a xanthine oxidase inhibitor which is administered orally.

It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[2]

Medical uses[edit]

Gout and hyperuricemia[edit]

Allopurinol is used in chronic gout to prevent future attacks. It does not alleviate acute attacks of gout and there is currently controversy over the issue of whether it can actually make acute gout attacks worse initially.[3][medical citation needed]

Tumor lysis syndrome[edit]

Allopurinol was also commonly used to treat tumor lysis syndrome in chemotherapeutic treatments, as these regimens can rapidly produce severe acute hyperuricemia, although it has gradually been replaced by urate oxidase therapy.[4]

Inflammatory bowel disease[edit]

Allopurinol cotherapy is used to improve outcomes for people with inflammatory bowel disease and Crohn's disease who do not respond to thiopurine monotherapy.[5][6] Cotherapy has also been shown to greatly improve hepatoxicity side effects in treatment of IBD.[7] Cotherapy invariably requires dose reduction of the thiopurine, usually to one-third of the standard dose depending upon the patient's genetic status for thiopurine methyltransferase.[8]

Reperfusion injury[edit]

Other established indications for allopurinol therapy include ischemic reperfusion injury, kidney stones with a uric acid component (uric acid nephrolithiasis), and protozoal infections (leishmaniasis).[medical citation needed]


Allopurinol is used as an add-on drug for refractory epilepsy, because it is an adenosine agonist, which inhibits glutamine release from excitatory neurons, but does not change the plasma concentration of other epilepsy drugs.[9]

Side effects[edit]

Because allopurinol is not a uricosuric, it can be used in patients with poor kidney function. However, allopurinol has two important disadvantages.

First, its dosing is complex.[10] Second, some patients are hypersensitive to the drug,[11] therefore its use requires careful monitoring. Allopurinol has rare but potentially fatal adverse effects involving the skin. The most serious adverse effect is a hypersensitivity syndrome consisting of fever, skin rash, eosinophilia, hepatitis, worsened renal function, and, in some cases, allopurinol hypersensitivity syndrome.[11] Allopurinol is one of the drugs commonly known to cause Stevens–Johnson syndrome and toxic epidermal necrolysis, two life-threatening dermatological conditions.[12] More common is a less-serious rash that leads to discontinuing this drug.

More rarely, allopurinol can also result in the depression of bone marrow elements, leading to cytopenias, as well as aplastic anemia. Moreover, allopurinol can also cause peripheral neuritis in some patients, although this is a rare side effect. Another side effect of allopurinol is interstitial nephritis.[13]

It is suspected to cause congenital malformations in a newborn infant whose mother was on allopurinol treatment through the pregnancy, and should be avoided whenever possible by women trying to conceive or during pregnancy.[14]


A common misconception is that allopurinol is metabolized by its target, xanthine oxidase, but this action is principally carried out by aldehyde oxidase.[15] The active metabolite of allopurinol is oxypurinol, which is also an inhibitor of xanthine oxidase. Allopurinol is almost completely metabolized to oxypurinol within two hours of oral administration, whereas oxypurinol is slowly excreted by the kidneys over 18–30 hours. For this reason, oxypurinol is believed responsible for the majority of allopurinol's effect.[16]

Mechanism of action[edit]

Allopurinol is a purine analog; it is a structural isomer of hypoxanthine (a naturally occurring purine in the body) and is an inhibitor of the enzyme xanthine oxidase.[1] Xanthine oxidase is responsible for the successive oxidation of hypoxanthine and xanthine, resulting in the production of uric acid, the product of human purine metabolism.[1] In addition to blocking uric acid production, inhibition of xanthine oxidase causes an increase in hypoxanthine and xanthine. While xanthine cannot be converted to purine ribotides, hypoxanthine can be salvaged to the purine ribotides adenosine and guanosine monophosphates. Increased levels of these ribotides may cause feedback inhibition of amidophosphoribosyl transferase, the first and rate-limiting enzyme of purine biosynthesis. Allopurinol, therefore, decreases uric acid formation and may also inhibit purine synthesis.[17]


The HLA-B*5801 allele is a genetic marker for allopurinol-induced severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN).[18][19] The frequency of the HLA-B*5801 allele varies between ethnicities: Han Chinese and Thai populations have HLA-B*5801 allele frequencies of around 8%, as compared to European and Japanese populations, who have allele frequencies of around 1.0% and 0.5%, respectively.[20] The increase in risk for developing allopurinol-induced SJS or TEN in individuals with the HLA-B*5801 allele (as compared to those who do not have this allele) is very high, ranging from a 40-fold to a 580-fold increase in risk, depending on ethnicity.[18][19] Currently, the FDA-approved drug label for allopurinol does not contain any information regarding the HLA-B*5801 allele, though FDA scientists did publish a study in 2011 which reported a strong, reproducible and consistent association between the allele and allopurinol-induced SJS and TEN.[21] However, the American College of Rheumatology recommends screening for HLA-B*5801 in high-risk populations (e.g. Koreans with stage 3 or worse chronic kidney disease and those of Han Chinese and Thai descent), and prescribing patients who are positive for the allele an alternative drug.[22] The Clinical Pharmacogenetics Implementation Consortium guidelines state that allopurinol is contraindicated in known carriers of the HLA-B*5801 allele.[23][24]


Allopurinol was first synthesized and reported in 1956 by Roland K. Robins (1926-1992), in a search for antineoplasitic agents.[25] Because allopurinol inhibits the breakdown (catabolism) of the thiopurine drug mercaptopurine, and it was later tested by Wayne Rundles, in collaboration with Gertrude Elion's lab at Wellcome Research Laboratories to see if it could improve treatment of acute lymphoblastic leukemia by enhancing the action of mercaptopurine.[26] However, no improvement in leukemia response was noted with mercaptopurine-allopurinol co-therapy, so that work turned to other compounds and the team then started testing allopurinol as a potential for gout.[27] Allopurinol was first marketed as a treatment for gout in 1966.[26]

Society and culture[edit]

Pure allopurinol is a white powder.

Allopurinol has been marketed in the United States since August 19, 1966, when it was first approved by FDA under the trade name Zyloprim.[28] Allopurinol was marketed at the time by Burroughs-Wellcome. Allopurinol is now a generic drug sold under a variety of brand names, including Allohexal, Allosig, Milurit, Alloril, Progout, Ürikoliz, Zyloprim, Zyloric, Zyrik, and Aluron.[29]


Allopurinol can be used in patients with poor kidney function. A study of allopurinol use in patients with chronic kidney disease suggested, "Allopurinol decreases C-reactive protein and slows the progression of renal disease in patients with chronic kidney disease. In addition, it reduces cardiovascular and hospitalization risk in these subjects."[30]

A mechanistic study in patients with chronic heart failure has shown the actions of allopurinol may be due to its inhibition of xanthine oxidase rather than a urate-lowering effect. This study also showed, for the first time, a high dose (600 mg) is significantly better at improving endothelial function compared to standard doses.[31]

A recent study has suggested allopurinol may help reduce the effects of angina in ischaemic heart disease by reducing the workload on the heart.[32]

Allopurinol can decrease blood pressure, thus reducing hypertension.[33]


  1. ^ a b c Pacher, P.; Nivorozhkin, A; Szabó, C (2006). "Therapeutic Effects of Xanthine Oxidase Inhibitors: Renaissance Half a Century after the Discovery of Allopurinol". Pharmacological Reviews 58 (1): 87–114. doi:10.1124/pr.58.1.6. PMC 2233605. PMID 16507884. 
  2. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
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  9. ^ Drug-Resistant Epilepsy N Engl J Med 2011; 365:2238-2240December 8, 2011
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Further reading[edit]

  • The Third International Thiopurine Symposium 2010, published in RAMB, for information on Allopurinol co-therapy: [1]

External links[edit]