Summary for UKPID


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph has been produced by staff of a National Poisons
    Information Service Centre in the United Kingdom.  The work was
    commissioned and funded by the UK Departments of Health, and was
    designed as a source of detailed information for use by poisons
    information centres.

    Peer review group: Directors of the UK National Poisons Information


         Proprietary    Zyloric(R), Zyloric-300(R)
         Generic        Allopurinol

    Chemical group / family

         Antigout agents - xanthine oxidase inhibitor
         BNF 10.1.4

    Reference number

         CAS 315-30-3
         CAS 17795-21-0

    Manufacturer / supplier

         Wellcome UK
         The Wellcome Foundation Ltd
         Hale Court Greencourts Business Park
         Styal Road
         M22 5LQ

         Tel:      0161 435 9372
                   01707 398085 (24hr emergencies)
         Fax:      0161 435 9363


         Tablets 100mg bottle of 100 tablets
         Tablets 300mg calendar pack of 2x14 tablets
         Also available from generic drug companies in various pack sizes.

    Physico-chemical properties:

    Chemical structure
         1H-Pyrazolo[3,4-d]pyrimidin-4-ol, C5H4N4O

    Physical state at room temp
         white / almost white crystalline powder, odourless

    Molecular weight


         in alcohol  >1 in 10 000
         in water    >1 in 10 000



         Prophylaxis of gout and of uric acid and calcium oxalate renal

    Therapeutic Dosage

         Initially 100mg daily as a single dose, after food, gradually
         increased over 1-3 weeks according to the plasma or urinary uric
         acid concentration to about 300mg daily. Usual maintenance dose
         200-600mg, rarely 900mg daily, divided into doses of not more
         than 300mg.
         Child (in neoplastic conditions, enzyme disorders) 10-20mg/kg


         Known intolerance of allopurinol.
         Not for treatment of the acute attack of gout.

    Hazard / risk classification



    Absorption               80-90%
    Volume of distribution   1.6 Lkg-1
    Metabolism               approx 80%
    Elimination              10% excreted in urine unchanged, 70% excreted
                             as allopurinol
    Plasma half-life         allopurinol    0.5-2h
                             oxypurinol     10-40h

    Special populations

    Pregnancy - little data available, avoid use.

    Hepatic disease - patients may have a higher risk of adverse reactions

    Renal disease - Reduce dose in renal impairment as increased risk of
    adverse reactions. Reduced rate of elimination and possible
    precipitation of oxypurinol or xanthine calculi. Reduce risks of
    calculi by maintaining sufficient hydration to maintain daily urinary
    output above 2l and ensuring that the urine remains slightly alkaline.

    Breast milk - Allopurinol and oxypurinol are excreted in breast milk.
    The effects on the infant are unknown.



    Adverse effects

         Skin rashes are the most common side-effect. These are generally
         maculopapular or pruritic, but more serious hypersensitivity
         reactions may occur and include exfoliative rashes, the
         Stevens-Johnson syndrome, and toxic epidermal necrolysis.

         Further symptoms of hypersensitivity include fever, chills,
         leucopenia or leucocytosis, eosinophilia, arthralgia, and
         vasculitis leading to renal and hepatic damage. These
         hypersensitivity reactions may be severe, even fatal, and
         patients with hepatic or renal impairment are at special risk.


         ACE Inhibitors                Increased risk of toxicity with
                                       captopril, especially in patients
                                       with renal impairment.

         Adenine arabinoside           Enhanced toxic effects as half-life

         Salicylates and               Decreased therapeutic activity of
         uricosuric agents             allopurinol.

         Chlorpropamide                Increased risk of prolonged
                                       hypoglycaemic activity in patients
                                       with poor renal function.

         Coumarin anticoagulants       Effects of anticoagulants possibly

         Cyclosporin                   Plasma levels possibly increased -
                                       risk of nephrotoxicity.

         Cytotoxics                    Effects of azathioprine and
                                       mercaptopurine enhanced with
                                       increased toxicity.

         Phenytoin                     Inhibition of hepatic oxidation may
                                       occur, but may not be clinically

         Theophylline                  No clinical reports of

    Mechanism of action / toxicity

    Acute ingestion

    Accidental or deliberate ingestion of up to 5g (Manufacturer's data
    sheet), and in one case 22.5g (Ferner et al, 1988), has been reported,
    with low toxicity.

    Chronic ingestion

    Toxicity on therapeutic doses is more common in patients with renal


    Nausea, vomiting, diarrhoea, dizziness, headache, somnolence and
    abdominal pain. Rarely renal insufficiency and hepatitis.


    Unlikely to be required. Recovery follows general supportive measures.
    In cases of massive overdose the patient's renal and hepatic function
    should be evaluated. Adequate hydration to maintain optimum diuresis
    facilitates excretion of allopurinol and its metabolites.

    Case data

    1.   A 15 year old girl ingested 22.5g (416mg/kg) of allopurinol,
    received gastric lavage within 3 hours of ingestion and 50g of
    activated charcoal. No signs of toxicity developed. Minor increases in
    plasma phosphate (to 1.43 mmol/L) and alkaline phosphatase (to 129 IU)
    were noted over the next 4 days. The half-life of allopurinol was 3.6
    hours, and oxypurinol 26 hours. (Ferner et al, 1988).

    2.   An 11 year old boy with acute lymphoblastic leukaemia presented
    in renal failure    after having been treated with allopurinol
    900mg/day for 3 months. He failed to respond to peritoneal dialysis,
    and died on the seventh day post-admission. Autopsy revealed an
    obstructive uropathy, focal ephrocalcinosis, and multiple small stones
    in the calyces of both kidneys. The stones were found to contain 82%
    xanthine, 15% oxypurinol, and 3% hypoxanthine. Uric acid and
    allopurinol were not detected (Potter & Silvidi, 1987).

    3.   A 79 year old man taking allopurinol of unknown dosage and
    duration developed general malaise, weakness and anorexia. The initial
    impression was acute hepatitis. Liver function tests revealed the
    following: Total bilirubin 1.3mg/dL, LDH 1957 IU/L, SGOT 1487 IU/L,
    SGPT 535 IU/L, and alkaline phosphatase 331 IU/L. Despite aggressive
    treatment, the patient died on the third hospital day. Autopsy showed
    hepatic toxic centrilobular necrosis. An antemortum blood sample was
    found to contain allopurinol 230.8mcg/ml; normal peak serum levels
    after a typical 300mg dose are 3 to 9mcg/ml ( Tam & Carroll, 1989).

    Other toxicological data

    Carcinogenicity     Longterm studies in rodents showed no

    Mutagenicity        No mutagenicity showed in human lymphocytes

    Teratogenicity      There are no controlled studies on the use of
                        allopurinol in human pregnancy or possible effects
                        on fertility / male reproduction. There are 2
                        published reports of normal outcomes following
                        exposure during pregnancy.
                        Animal studies: Facial clefts and minor skeletal
                        defects have been reported in mice exposed to
                        allopurinol, but no teratogenic effects were
                        reported after administration of high doses in
                        rats and rabbits.


    Kathryn Pughe, BSc (Hons) MRPharmS

    National Poisons Information Service (Newcastle Centre)
    Regional Drug & Therapeutics Centre
    Wolfson Building
    Claremont Place
    Newcastle upon Tyne
    NE1 4LP

    This monograph was produced by the staff of the Newcastle Centre of
    the National Poisons Information Service in the United Kingdom. The
    work was commissioned and funded by the UK Departments of Health, and
    was designed as a source of detailed information for use by poisons
    information centres.

    Peer review was undertaken by the Directors of the UK National Poisons
    Information Service.

    Last updated January 1997



    1.   ABPI Compendium of Data Sheets and Summaries of Product
         Characteristics. Datapharm Publications Ltd. 1996-97.

    2.   AHFS Drug Information. McEvoy GK (Ed.) 1996.

    3.   British National Formulary. Number 32 (September 1996). British
         Medical Association and Royal Pharmaceutical Society.

    4.   Dollery C. Therapeutic Drugs. Churchill Livingstone. 1991.

    5.   Ellenhorn MJ. Ellenhorn's Medical Toxicology: Diagnosis and
         Treatment of Human Poisoning. 2nd Edition 1997. Williams &

    6.   Martindale : The Extra Pharmacopoeia. 31st Edition. Reynolds JEF
         (Ed.) Pharmaceutical Press. 1996.


    1.   Ferner RE, Simmonds HA, Bateman DN. Allopurinol kinetics after
         massive overdosage. Hum Toxicol 1988; 7: 293-4.

    2.   Potter JL and Silvidi AA. Xanthine lithiasis, nephrocalcinosis,
         and renal failure in a leukaemia patient treated with
         allopurinol. Clin Chem 1987; 33: 2314-6.

    3.   Tam S and Carroll W. Allopurinol hepatotoxicity. Am J Med 1989;

    Computer databases

    1.   Poisindex System(R), Micromedex inc., Denver Colorado, Edition
         Expires 3/97.

    2.   Reprotox System(R), Micromedex inc., Denver Colorado, Edition
         Expires 3/97.

    3.   TOXBASE, National Poisons Information Service, 1996.