Allopurinol is a xanthine oxidase inhibitor prescribed for the long-term management of hyperuricemia and its complications, most notably gout. It works by reducing the production of uric acid in the body, thereby lowering serum urate levels and preventing the formation of urate crystals. This medication is a cornerstone in prophylactic therapy, helping to prevent acute gout attacks, tophi formation, and uric acid nephrolithiasis. Its use requires careful patient selection, dose titration, and monitoring to ensure efficacy and minimize the risk of adverse reactions.

Features

• Active Ingredient: Allopurinol
• Drug Class: Xanthine oxidase inhibitor
• Available Formulations: Oral tablets (100 mg and 300 mg)
• Mechanism of Action: Inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid
• Bioavailability: Approximately 90% when administered orally
• Half-life: Parent drug: 1–3 hours; active metabolite oxipurinol: 18–30 hours
• Metabolism: Hepatic, to active metabolite oxipurinol
• Excretion: Primarily renal

Benefits

• Prevents recurrent acute gout attacks by maintaining serum uric acid levels below the saturation point for crystal formation
• Reduces the risk of chronic gouty arthropathy and joint damage
• Helps resolve existing tophi and prevents the formation of new ones
• Lowers the incidence of uric acid kidney stones
• May be used as a prophylactic agent in patients undergoing chemotherapy to prevent tumor lysis syndrome-associated hyperuricemia
• Provides a well-tolerated, once-daily dosing option for most patients after appropriate titration

Common use

Allopurinol is primarily indicated for:

• Chronic management of gout and hyperuricemia secondary to various conditions
• Prophylaxis of acute gout flares (note: not for treatment of acute attacks)
• Prevention of uric acid nephropathy in patients with neoplastic disease receiving anticancer therapy
• Management of recurrent uric acid stone formation
• Off-label uses may include Lesch-Nyhan syndrome and certain forms of epilepsy

Dosage and direction

Initial dose: Typically 100 mg once daily, with gradual titration based on serum uric acid levels.
Maintenance dose: 200–600 mg daily for mild gout; 400–800 mg daily for moderate to severe tophaceous gout.
Dosing in renal impairment: Requires significant adjustment. For CrCl 10–20 mL/min: max 200 mg/day; CrCl <10 mL/min: max 100 mg/day or longer intervals between doses.
Administration: Take with food or milk to minimize gastric upset. Maintain adequate hydration (2–3 L fluid daily unless contraindicated).
Titration: Increase by 100 mg every 1–4 weeks until target serum uric acid (<6 mg/dL) is achieved.

Precautions

• Initiate therapy only when acute gout attack has completely subsided
• Monitor serum uric acid levels periodically to assess efficacy
• Regular monitoring of renal function and liver enzymes recommended
• May initially precipitate acute gout attacks; concurrent prophylaxis with NSAIDs or colchicine is often recommended during the first 3–6 months of therapy
• Use with caution in patients with hepatic impairment
• Screen for HLA-B*5801 allele before initiation in populations at higher risk for severe cutaneous adverse reactions (e.g., Han Chinese, Korean, Thai descent)

Contraindications

• Hypersensitivity to allopurinol or any component of the formulation
• Patients who have experienced severe reactions to allopurinol (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Asymptomatic hyperuricemia (except during chemotherapy)
• Concurrent use with didanosine

Possible side effect

Common (≥1%):

• Skin rash (discontinue immediately if rash occurs)
• Nausea, vomiting, diarrhea
• Elevated liver enzymes
• Drowsiness, headache

Serious (<1% but require immediate medical attention):

• Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)
• Hepatotoxicity, including granulomatous hepatitis and hepatic necrosis
• Bone marrow suppression: leukopenia, thrombocytopenia, agranulocytosis
• Eosinophilia, vasculitis
• Peripheral neuropathy
• Renal impairment, including interstitial nephritis

Drug interaction

• Azathioprine/6-mercaptopurine: Allopurinol inhibits their metabolism, increasing toxicity—reduce dose by 65–75%
• Warfarin: May enhance anticoagulant effect—monitor INR closely
• ACE inhibitors: Increased risk of hypersensitivity reactions
• Diuretics (especially thiazides): May increase risk of allopurinol hypersensitivity and reduce efficacy
• Ampicillin/amoxicillin: Increased incidence of skin rash
• Cyclophosphamide: May enhance bone marrow suppression
• Theophylline: Increased serum levels possible
• Didanosine: Contraindicated due to increased toxicity

Missed dose

Take the missed dose as soon as remembered unless it is almost time for the next scheduled dose. Do not double the dose to make up for a missed one. Maintain regular dosing schedule to ensure consistent uric acid suppression.

Overdose

Symptoms may include nausea, vomiting, diarrhea, dizziness, and oliguria. Massive overdose may lead to acute renal failure. Management is supportive: gastric lavage if presented early, adequate hydration, and hemodialysis may be effective for removing allopurinol and oxipurinol. There is no specific antidote.

Storage

Store at controlled room temperature (20–25°C or 68–77°F). Protect from light and moisture. Keep in original container, tightly closed. Keep out of reach of children and pets. Do not use after expiration date.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting, changing, or stopping any medication. The prescribing physician should determine the appropriate therapy based on individual patient characteristics. Not all side effects or interactions are listed here.

Reviews

Clinical evidence consistently supports allopurinol’s efficacy in maintaining serum uric acid levels below 6 mg/dL in approximately 80-90% of appropriately selected patients. Long-term studies demonstrate significant reduction in gout flare frequency, tophi resolution, and improved quality of life. The medication is generally well-tolerated with proper dose titration and monitoring, though the risk of severe cutaneous adverse reactions, while rare, necessitates careful patient selection and education.