Allopurinol for managing gout, cancer-related hyperuricemia and calcium oxalate kidney stones

Allopurinol tablets are used to manage high uric acid levels in adults and children under specific conditions, including gout symptoms, cancer therapy-induced hyperuricemia, and recurrent kidney stones caused by calcium oxalate. It works by inhibiting the enzyme xanthine oxidase, reducing uric acid production.

• Gout: Management of adults showing signs and symptoms of primary or secondary gout, including acute attacks, tophi, joint destruction, uric acid kidney stones, and related kidney issues.
• Cancer-related hyperuricemia: Management of adult and pediatric patients with leukemia, lymphoma, or solid tumors undergoing cancer therapy that elevates serum and urinary uric acid.
• Recurrent calcium oxalate kidney stones: For adults with recurrent calcium oxalate stones and elevated daily uric acid excretion (>800 mg/day in men, >750 mg/day in women) despite lifestyle changes.

Limitations: Not recommended for treating asymptomatic hyperuricemia.

Allopurinol

Allopurinol works by inhibiting xanthine oxidase, an enzyme responsible for producing uric acid in the body. By blocking this enzyme, the medication lowers uric acid levels in the blood and urine, helping to prevent gout attacks, kidney stone formation, and complications associated with increased uric acid from cancer treatment.

For Gout in Adults with Normal Kidney Function

• Start with 100 mg orally once daily.
• Increase by 100 mg increments weekly until serum uric acid is 6 mg/dL or less, with a maximum dose of 800 mg daily.
• Doses above 300 mg should be divided.

For Adults with Gout and Renal Impairment

• Start with 50 mg once daily.
• Titrate by 50 mg every 2 to 4 weeks until target serum uric acid is reached.
• Initial and maintenance doses depend on estimated glomerular filtration rate (eGFR):

For Hyperuricemia Associated with Cancer Therapy

• Adults: 300 mg to 800 mg orally daily.
• Pediatric: 100 mg/m2 orally every 8 to 12 hours (up to 10 mg/kg/day; max 800 mg/day).
• Initiate 24 to 48 hours before chemotherapy causing tumor cell lysis.
• Adjust doses for renal impairment based on eGFR:

For Recurrent Calcium Oxalate Calculi

• Initial dose: 200 mg to 300 mg orally daily divided or single dose, adjusted as needed based on 24-hour urinary urate levels.

Additional Instructions

• Baseline tests before starting therapy: serum uric acid, blood counts, liver and kidney function.
• Flare prophylaxis with colchicine or NSAIDs recommended at start of treatment and continued until stable control of gout flares.
• Maintain daily urine output of at least 2 liters, preferably with neutral or slightly alkaline urine.
• If a dose is missed, do not double the next dose.
• Take with or after meals for better tolerance.
• Use caution and monitor kidney function closely in patients with renal impairment.

Use is contraindicated in patients with known hypersensitivity to allopurinol or any of its ingredients.

Serious Skin Reactions and Hypersensitivity

• Allopurinol may cause severe, sometimes fatal dermatologic reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS.
• Discontinue immediately if rash or signs of hypersensitivity appear.
• Patients with the HLA-B*58:01 allele are at higher risk; screening recommended in high-prevalence populations (e.g., African, Asian, Native Hawaiian/Pacific Islander ancestry).
• Concomitant use with thiazide diuretics, bendamustine, ampicillin, or amoxicillin may increase risk of severe rash.

Gout Flares

• Flares can occur when starting treatment due to urate mobilization.
• Use prophylactic treatment with colchicine or anti-inflammatory drugs to reduce flare risk.
• Do not stop allopurinol if a flare occurs; manage flare concurrently.

Kidney Effects

• Allopurinol may worsen kidney function or cause acute kidney injury due to xanthine stone formation or urate precipitation, especially in patients with pre-existing kidney disease or those receiving uricosuric agents.
• Monitor kidney function frequently during early treatment.
• Encourage high fluid intake and maintain alkaline urine to minimize risk.

Hepatotoxicity

• Cases of reversible liver toxicity and asymptomatic liver enzyme elevations have been reported.
• Evaluate liver function if symptoms like anorexia, weight loss, or itching occur.

Myelosuppression

• Bone marrow suppression manifesting as anemia, leukopenia, or thrombocytopenia may occur, sometimes months or years after starting therapy.
• Concurrent use with cytotoxic drugs may increase risk; monitor blood counts more frequently.

CNS Effects

• Drowsiness, somnolence, and dizziness have been reported; caution with activities requiring alertness.

Common Adverse Reactions

• Skin rash
• Drowsiness, somnolence, dizziness

Serious Adverse Reactions

• Severe hypersensitivity reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis, and DRESS.
• Myelosuppression (anemia, leukopenia, thrombocytopenia)
• Hepatotoxicity
• Nephrotoxicity, including acute kidney injury

• Mercaptopurine and Azathioprine: Allopurinol increases their exposure, raising myelosuppression risk. Dosage reductions of these drugs are needed when used together.
• Thiazide Diuretics, Bendamustine, Ampicillin, Amoxicillin: Concurrent use increases risk of severe skin rash or hypersensitivity reactions.
• CNS Depressants and Alcohol: Effects may be additive, increasing drowsiness or dizziness.