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Allopurinol, sold under the brand name Zyloprim among others, is a medication used to decrease high blood uric acid levels.
Common side effects when used by mouth include itchiness and rash.
Allopurinol was approved for medical use in the United States in 1966.
Contents
1 Medical uses
1.1 Gout
1.2 Tumor lysis syndrome
1.3 Inflammatory bowel disease
1.4 Epilepsy
2 Contraindications and drug interactions
3 Side effects
4 Pharmacology
4.1 Mechanism of action
4.2 Pharmacogenetics
5 History
6 Society and culture
6.1 Formulations
6.2 Brands
7 See also
8 References
9 External links
Medical uses
Gout
Allopurinol is used to reduce urate formation in conditions where urate deposition has already occurred or is predictable. The specific diseases and conditions where it is used include gouty arthritis, skin tophi, kidney stones, idiopathic gout; uric acid lithiasis; acute uric acid nephropathy; neoplastic disease and myeloproliferative disease with high cell turnover rates, in which high urate levels occur either spontaneously, or after cytotoxic therapy; certain enzyme disorders which lead to overproduction of urate, for example: hypoxanthine-guanine phosphoribosyltransferase, including Lesch–Nyhan syndrome ; glucose 6-phosphatase including glycogen storage disease ; phosphoribosyl pyrophosphate synthetase, phosphoribosyl pyrophosphate amidotransferase ; adenine phosphoribosyltransferase.
It is also used to treat kidney stones caused by deficient activity of adenine phosphoribosyltransferase.
Tumor lysis syndrome
Allopurinol was also commonly used to treat tumor lysis syndrome in chemotherapeutic treatments, as these regimens can rapidly produce severe acute hyperuricemia,
Inflammatory bowel disease
Allopurinol cotherapy is used to improve outcomes for people with inflammatory bowel disease and Crohn’s disease who do not respond to thiopurine monotherapy.
Epilepsy
Allopurinol is used as an add-on drug for refractory epilepsy, because it is an adenosine agonist, which inhibits glutamate release from excitatory neurons, but does not change the plasma concentration of other epilepsy drugs.
Contraindications and drug interactions
Allopurinol should not be given to people who are allergic to it.
Drug interactions are extensive, and are as follows:
Azathioprine and 6-mercaptopurine : Azathioprine is metabolised to 6-mercaptopurine which in turn is inactivated by the action of xanthine oxidase – the target of allopurinol. Giving allopurinol with either of these drugs at their normal dose will lead to overdose of either drug; only one-quarter of the usual dose of 6-mercaptopurine or azathioprine should be given;
Didanosine : plasma didanosine Cmax and AUC values were approximately doubled with concomitant allopurinol treatment; it should not be co-administered with allopuroinol and if it must be, the dose of should be reduced and the person should be closely monitored.
Allopurinol may also increase the activity or half-life of the following drugs, in order of seriousness and certainty of the interaction:
Ciclosporin
Coumarin anticoagulants, such as warfarin (reported rarely, but is serious when it occurs)
Vidarabine
Chlorpropamide
Phenytoin
Theophylline
Cyclophosphamide, doxorubicin, bleomycin, procarbazine, mechlorethamine
Co-administration of the following drugs may make allopurinol less active or decrease its half-life:
Salicylates and medicines that increase the secretion of uric acid
furosemide (see more on diuretics below)
Co-administration of the following drugs may cause hypersensitivity or skin rash:
Ampicillin and amoxicillin
Diuretics, in particular thiazides, especially in renal impairment
Angiotensin-converting-enzyme inhibitors (ACE inhibitors)
Side effects
Because allopurinol is not a uricosuric, it can be used in people with poor kidney function. However, allopurinol has two important disadvantages.
First, its dosing is complex.
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, and worsened renal function.
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.
Pharmacology
A common misconception is that allopurinol is metabolized by its target, xanthine oxidase, but this action is principally carried out by aldehyde oxidase.
Mechanism of action
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.
Pharmacogenetics
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).
History
Allopurinol was first synthesized and reported in 1956 by Roland K. Robins (1926-1992), in a search for antineoplastic agents.
Society and culture
Pure allopurinol is a white powder.
Formulations
Allopurinol is sold as an injection for intravenous use
Brands
Allopurinol has been marketed in the United States since August 19, 1966, when it was first approved by FDA under the trade name Zyloprim.
See also
Lesinurad/allopurinol, a fixed-dose combination drug

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