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Allopurinol

Allopurinol

Zyloprim Lopurin Aloprim

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Updated: December 06, 2025

Overview

Allopurinol is a xanthine oxidase inhibitor primarily used in the management of chronic gout and hyperuricemia. It works by reducing uric acid production through inhibition of the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. This medication is particularly valuable for patients with recurrent gout attacks, tophi, or uric acid kidney stones. It also plays an important role in preventing tumor lysis syndrome in cancer patients undergoing chemotherapy, where rapid cell death can lead to dangerous uric acid levels.

Drug Class

Xanthine oxidase inhibitor Antigout agent Purine analog

Mechanism of Action

Competitive inhibition of xanthine oxidase: • Blocks conversion of hypoxanthine to xanthine • Inhibits oxidation of xanthine to uric acid • Reduces total uric acid production • Increases reutilization of hypoxanthine and xanthine for nucleotide synthesis

Pharmacokinetics

Absorption: ~90% oral bioavailability Distribution: Widely distributed in tissues • Minimal protein binding (20-30%) • Volume of distribution: 1.6 L/kg Metabolism: Primarily metabolized to oxypurinol (active metabolite) via aldehyde oxidase Excretion: Renal excretion (70-80% as metabolites) • 10-20% excreted unchanged in urine Half-life: Allopurinol: 1-3 hours Oxypurinol: 18-30 hours (prolonged in renal impairment)

Pharmacodynamics

• Reduces serum uric acid within 2-3 days • Maximum effect seen in 1-3 weeks • Prevents formation of urate crystals • May initially increase acute gout attacks during early treatment (mobilization of urate stores)

Indications

• Management of chronic gout and hyperuricemia • Prevention of uric acid nephrolithiasis • Prophylaxis of tumor lysis syndrome in cancer patients • Treatment of recurrent calcium oxalate calculi in hyperuricosuric patients • Management of hyperuricemia secondary to myeloproliferative disorders

Contraindications

Absolute: • Hypersensitivity to allopurinol • Concomitant use with azathioprine or mercaptopurine Relative: • Severe renal impairment (CrCl <20 mL/min) • Asymptomatic hyperuricemia • History of severe cutaneous adverse reactions

Dosage & Administration

Gout/Hyperuricemia: • Initial: 100 mg daily, increased weekly by 100 mg • Maintenance: 200-600 mg/day (maximum 800 mg/day) Tumor Lysis Prophylaxis: • 200-400 mg/m²/day (maximum 600 mg/day) • Start 2-3 days before chemotherapy Renal Impairment: • CrCl 10-20 mL/min: 100-200 mg/day • CrCl <10 mL/min: 100 mg/day or less

Special Populations

Pediatric: Limited use; 10 mg/kg/day for tumor lysis prophylaxis Geriatric: Start with lower doses (50-100 mg/day) Renal impairment: Dose reduction required • Monitor serum uric acid and creatinine Hepatic impairment: Use with caution • Monitor liver function tests

Adverse Effects

Common (>10%): • Maculopapular rash • Nausea/vomiting • Diarrhea • Elevated liver enzymes Serious (<1%): • Stevens-Johnson syndrome (SJS) • Toxic epidermal necrolysis (TEN) • Allopurinol hypersensitivity syndrome (fever, eosinophilia, hepatitis) • Bone marrow suppression

Drug Interactions

• Azathioprine/6-Mercaptopurine: Increased toxicity (require 75% dose reduction) • Warfarin: Enhanced anticoagulant effect • Ampicillin/Amoxicillin: Increased risk of skin rash • Diuretics: May reduce allopurinol efficacy • Theophylline: Increased theophylline levels

Warnings & Precautions

• Black Box Warning: Severe skin reactions (SJS, TEN) • Gradual dose titration to prevent acute gout attacks • Monitor for hypersensitivity reactions • Hydration important to prevent xanthine nephropathy • Caution in patients with bone marrow suppression

Pregnancy & Lactation

Pregnancy: Category C • Use only if potential benefit justifies risk • Limited human data Lactation: Excreted in breast milk • Consider discontinuing nursing • Monitor infant for rash/diarrhea

Monitoring Parameters

• Serum uric acid levels (target <6 mg/dL) • Renal function tests • Liver function tests • Complete blood count • Skin examination for rash • Uric acid crystals in urine (if applicable)

Patient Counseling

• Take with food to reduce GI upset • Maintain adequate hydration (2-3 L/day) • Report any skin rash immediately • May experience initial gout flare-ups (prophylactic NSAIDs/colchicine often prescribed) • Avoid high-purine foods during treatment initiation • Do not discontinue abruptly

Storage & Stability

• Store at 20-25°C (68-77°F) • Protect from light and moisture • Stable in oral suspension for 7 days at room temperature • Do not freeze

Clinical Pearls

• Start with low dose (100 mg/day) to prevent acute gout flares • Not effective for acute gout treatment • Consider checking thiopurine methyltransferase (TPMT) status before coadministration with azathioprine • Hypersensitivity reactions more common in HLA-B*5801 positive patients • May take several months to dissolve existing tophi

References

• Lexicomp Drug Information: Allopurinol • UpToDate: Allopurinol drug monograph • FDA Prescribing Information: Zyloprim • Micromedex: Allopurinol therapeutic classification • American College of Rheumatology Gout Management Guidelines