Last updated: October 6, 2014

Trade Names: Zyloprim

Drug Class: Xanthine oxidase inhibitor; antigout agent

Preparations: 100- and 300-mg tablets

Dose: For prophylaxis of gout, initially use 100 mg/day, increased at 2-4 week intervals according to uric acid response. In the elderly and those with renal impairment, use 50 mg or less/day initially.

Common maintenance dose is 300 mg/day but more than 50% of patients require higher doses. Maximum recommended dose in patients without renal impairment is 800 mg/day.

If required in patients with renal impairment, allopurinol starting dose is modified according to creatinine clearance  – approximately 1.5 mg allopurinol/ml of creatinine clearance and no more than 50 mg a day. Based on uric acid response many patients with renal impairment can be carefully titrated to higher doses although final doses used are lower than in those without renal impairment and long term safety not established.

Indications: To treat hyperuricemia in patients with gout

Mechanism of Action: Inhibits formation of uric acid by inhibiting xanthine oxidase; has no anti-inflammatory activity

Contraindications: Previous hypersensitivity to allopurinol. Avoid concurrent azathioprine or mercaptopurine.

Precautions: Reduce dose in the elderly, patients on diuretics, and patients with renal impairment. Check HLA-B*5801 in patients of Asian ancestry before starting allopurinol and avoid if positive.

Pregnancy Risk: C

Monitoring: Monitor CBC and liver and renal function periodically, particularly in the first few months of treatment. Uric acid level guides the allopurinol dose. Aim to reduce uric acid concentration to <6 mg/dL in tophaceous disease.

Adverse Effects
Common: Acute gout may occur with increased frequency after starting allopurinol; thus, concurrent colchicine or NSAID treatment is used, particularly in first 3–6 months of therapy. Rash.
Rarely: Allopurinol hypersensitivity syndrome (exfoliative dermatitis/erythema multiforme, renal failure, hepatic impairment, vasculitis) is rare but may be fatal. Risk is increased in patients with impaired renal function, those receiving diuretics and those carrying HLA-B*5801. Desensitization has been tried in selected patients. Febuxostat, an alternative xanthine oxidase inhibitor, appears to be tolerated by many (but not all) patients who are allergic to allopurinol.  Agranulocytosis and aplastic anemia are rare.

Drug Interactions
Azathioprine and mercaptopurine: This is a potentially fatal interaction. Allopurinol decreases metabolism of these agents, leading to toxicity (bone marrow depression).
Warfarin: Anticoagulant effects potentiated
Ampicillin/amoxicillin: Increased risk of rash.
Diuretics: Increased risk of allopurinol toxicity
Chlorpropamide: Increased chlorpropamide serum half-life
Pegloticase: Urate lowering therapies including allopurinol should be discontinued prior to the use of pegloticase and should not be initiated during  pegloticase therapy.
Alcohol: Decreases effectiveness.

Patient Instructions: The drug needs to be taken every day (or as prescribed) to lower uric acid and thus prevent gout. It has no effect on the symptoms of gout and will not help when joints hurt. Discontinue drug and contact physician if rash develops. Do not drink alcohol.

Comments: Allopurinol is used primarily to lower the uric acid level in patients with recurrent attacks of acute gout (more than one per year) or patients with tophaceous gout. Start with low doses (to minimize risk of precipitating acute attacks and perhaps decrease risk of hypersensitivity) and increase at 4-8 week intervals if needed. Allopurinol is preferred over a uricosuric agent in patients with tophi, renal stones, and impaired renal function. Monitor serum uric acid and titrate dose with aim to decrease to 5–6 mg/dL. Failure to decrease uric acid often indicates poor compliance. Prevent acute attacks of gout with concurrent colchicine or NSAID treatment, particularly in first 3–6 months of therapy. High doses of aspirin are uricosuric but low doses increase uric acid levels.

Clinical Pharmacology: Oral absorption is 80%; 70% is metabolized to the active metabolite oxypurinol. Excretion is largely renal as oxypurinol, and accumulation occurs if renal function is impaired. Half-life of allopurinol is 2 hours and 20 hours for oxypurinol. Reduction of uric acid is noted within days, and the level may normalize within weeks. If allopurinol is discontinued, uric acid concentrations return to pretreatment levels in weeks.

Cost: $

Terkeltaub RA. Clinical practice. Gout. N Engl J Med 2003;349:1647–1655.PMID: 14573737
Khanna D, Fitzgerald JD, Khanna PP et al. 2012 American College of Rheumatology guidelines for management of gout. Arthritis Care Res 2012;64:1431-46.PMID:23024028
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 2012;93:153-8. PMID: 23232549 

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