Overview
Allopurinol is a xanthine oxidase inhibitor used to manage hyperuricemia in conditions like gout and during cancer therapy. It reduces uric acid production by inhibiting the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. This helps prevent gout attacks, tophi formation, and uric acid kidney stones.
Mechanism of Action
Allopurinol competitively inhibits xanthine oxidase, the enzyme that catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid. This reduces serum and urinary uric acid levels by decreasing uric acid production while increasing the excretion of more soluble hypoxanthine and xanthine precursors.
Indications
- Management of signs and symptoms of primary or secondary gout (acute attacks, tophi, joint destruction, uric acid lithiasis, and/or nephropathy)
- Management of hyperuricemia in pediatric and adult patients with leukemia, lymphoma, and solid tumor malignancies receiving cancer therapy that elevates serum and urinary uric acid levels
- Management of recurrent calcium oxalate calculi in adult patients with daily uric acid excretion exceeding 800 mg/day in males or 750 mg/day in females despite lifestyle modifications
Common Doses
- 100 mg
- 300 mg
Dosage
Typical adult starting dose is 100-300 mg daily, adjusted based on serum uric acid levels and clinical response. For gout, maintenance doses typically range from 200-600 mg daily, with maximum dose of 800 mg/day. For cancer therapy-induced hyperuricemia, higher doses may be required. Always start with lower doses and titrate upward.
Contraindications
- History of hypersensitivity reaction to allopurinol or any component of the formulation
Side Effects
- Skin rash (most common)
- Diarrhea
- Nausea
- Elevated liver enzymes (AST/ALT, alkaline phosphatase)
- Acute gout attacks
- Maculopapular rash
- Hepatitis
- Renal impairment
- Blood dyscrasias
Interactions
- Azathioprine/6-mercaptopurine: Allopurinol increases toxicity - reduce azathioprine/6-MP dose by 75%
- Warfarin: May enhance anticoagulant effect - monitor INR closely
- Ampicillin/amoxicillin: Increased risk of skin rash
- Diuretics: May increase risk of hypersensitivity reactions
- Theophylline: Allopurinol may increase theophylline levels
Counseling Points
- Take with plenty of fluids (8-10 glasses daily) to prevent kidney stones
- Report any skin rash, fever, or flu-like symptoms immediately
- Continue taking during gout attacks unless directed otherwise by healthcare provider
- Avoid high-purine foods (organ meats, sardines, anchovies) if prescribed for gout
- Regular monitoring of uric acid levels and liver/kidney function is required
- May take several weeks to months to see full benefit in gout management