Allopurinol

Generic Name

Allopurinol

Brand Names

Zyloprim

Aloprim (IV formulation in some markets)

Various generics available globally

Drug Class

Xanthine oxidase inhibitor

Antigout agent

Urate-lowering therapy (ULT)

Mechanism of Action

Allopurinol is a structural analog of hypoxanthine and works by competitively inhibiting the enzyme xanthine oxidase

Xanthine oxidase is responsible for converting hypoxanthine to xanthine and xanthine to uric acid

By inhibiting this enzyme, allopurinol reduces the production of uric acid in serum and urine

Lower serum uric acid levels result in decreased precipitation of monosodium urate crystals, which are the cause of gout attacks and urate nephropathy

Also reduces urinary uric acid excretion, helping prevent uric acid nephrolithiasis

Indications

Chronic Gout

First-line long-term therapy for the prevention of gout flares and tophaceous deposits in patients with recurrent attacks or tophi

Not for acute treatment but used chronically to prevent future attacks

Hyperuricemia Associated with Chemotherapy

Used to prevent tumor lysis syndrome by lowering uric acid levels in patients undergoing chemotherapy for leukemia, lymphoma, or other cancers with high tumor turnover

Recurrent Uric Acid Nephrolithiasis

Prevents recurrence of kidney stones in patients with elevated urinary uric acid levels

Hyperuricemia of Idiopathic or Genetic Origin

Used in Lesch-Nyhan syndrome or certain inborn errors of metabolism that result in increased purine turnover

Dosing and Administration

Chronic Gout (Adults)

Initial dose: 100 mg orally once daily

Titrate every 2 to 5 weeks by 100 mg increments based on serum uric acid level and tolerability

Usual maintenance dose: 200 to 600 mg/day in one or two divided doses

Severe cases may require up to 800 mg/day

Target serum uric acid <6 mg/dL

Tumor Lysis Syndrome (Adults)

Usual dose: 600–800 mg/day in divided doses starting 1–2 days prior to chemotherapy and continued during treatment

Ensure aggressive hydration

Pediatrics (Tumor Lysis Prevention)

<6 years: 150 mg/day in divided doses

6–10 years: 300 mg/day

10 years: Adult dosing applies

Renal Impairment

Dose adjustment required

CrCl 10–20 mL/min: 100 mg/day

CrCl <10 mL/min: 100 mg at extended intervals

Avoid accumulation of oxypurinol (active metabolite)

Hepatic Impairment

Use with caution and monitor liver function periodically

Administration Advice

Take after meals to reduce gastric upset

Maintain adequate fluid intake to prevent renal stone formation

Continue during acute gout flare if already started

Do not initiate during an acute gout attack to avoid worsening symptoms

Pharmacokinetics

Oral bioavailability ~80–90%

Peak plasma concentrations within 1.5 hours

Half-life of parent drug: 1–2 hours

Half-life of active metabolite (oxypurinol): 15–30 hours

Excreted primarily by kidneys

Contraindications

Hypersensitivity to allopurinol

Previous serious skin reaction (Stevens-Johnson syndrome or toxic epidermal necrolysis)

Concomitant use with didanosine (especially in renal dysfunction)

Precautions

Risk of severe hypersensitivity reactions including SJS/TEN, especially in those with HLA-B*58:01 allele (common in Han Chinese, Thai, and Korean ancestry)

Titrate dose slowly to reduce flare risk

Use prophylactic colchicine or NSAIDs for 3–6 months when initiating therapy

Adjust dose in renal impairment to avoid oxypurinol accumulation

Monitor hepatic function in long-term use

Stop at first sign of skin rash or allergic reaction

Caution in patients with bone marrow suppression or cytopenias

Adverse Effects

Common

Rash

Nausea

Diarrhea

Drowsiness

Headache

Elevated liver enzymes

Gout flares (during initiation)

Less Common

Leukopenia

Pruritus

Fever

Dyspepsia

Serious

Stevens-Johnson syndrome

Toxic epidermal necrolysis

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Hepatotoxicity

Interstitial nephritis

Agranulocytosis

Aplastic anemia

Peripheral neuropathy

Vasculitis

Anaphylaxis

Pregnancy and Lactation

Pregnancy

Category C (US)

Limited human data; animal studies show fetal toxicity at high doses

Used only if potential benefits justify the risk

Lactation

Excreted in breast milk in small quantities

Use caution when prescribing to nursing mothers

Consider alternatives if infant risk is a concern

Use in Special Populations

Geriatric

Increased risk of adverse effects

Use lowest effective dose

Monitor renal function closely

Renal Impairment

Dose adjustment required

Monitor for toxicity including hypersensitivity and bone marrow suppression

Hepatic Impairment

Use cautiously

Monitor liver enzymes during prolonged use

Drug Interactions

Azathioprine and Mercaptopurine

Allopurinol inhibits xanthine oxidase, the primary metabolic pathway for these drugs

Co-administration increases levels and toxicity (myelosuppression risk)

Reduce azathioprine or mercaptopurine dose to one-fourth if used together

Cyclophosphamide

Increased risk of bone marrow suppression

Thiazide Diuretics

May increase risk of allopurinol hypersensitivity reactions

Ampicillin/Amoxicillin

Increased incidence of rash when combined

Warfarin

May enhance anticoagulant effect – monitor INR closely

Theophylline

Allopurinol may reduce the clearance of theophylline – monitor serum levels

Chlorpropamide

Risk of prolonged hypoglycemia in renal impairment when used together

Monitoring Parameters

Serum uric acid levels

CBC with differential if on immunosuppressants

Renal function before initiation and regularly during therapy

Liver function tests periodically

Watch for signs of hypersensitivity (rash, fever, eosinophilia, liver dysfunction)

Uric acid levels should be reassessed after each dose adjustment

Formulations

Tablets: 100 mg, 300 mg

IV formulation (Aloprim): Used in tumor lysis syndrome in hospitalized patients

Store at room temperature

Protect from moisture and heat

Patient Counseling Points

Take medication daily as prescribed, even if asymptomatic

Do not stop or adjust dose without consulting doctor

Drink plenty of fluids to reduce risk of kidney stones

Inform doctor immediately of any rash, fever, or signs of allergic reaction

Avoid alcohol and high-purine foods which may trigger flares

Gout flares may temporarily worsen when initiating therapy – continue allopurinol and use anti-inflammatory agents as prescribed

Report unusual bleeding, signs of liver injury, or severe fatigue

Do not use over-the-counter cold medicines or antibiotics without informing your doctor

Inform your healthcare provider if taking azathioprine or mercaptopurine