Allopurinol

Allopurinol is a xanthine oxidase inhibitor prescribed for the long-term management of hyperuricemia, particularly in patients with gout, kidney stones, or those undergoing certain cancer treatments. By reducing the production of uric acid, it addresses the underlying metabolic imbalance rather than merely alleviating acute symptoms. This medication is a cornerstone of urate-lowering therapy, helping to prevent painful gout flares, tophi formation, and joint damage when used consistently under medical supervision.

Features

• Active ingredient: Allopurinol
• Drug class: Xanthine oxidase inhibitor
• Available formulations: 100 mg and 300 mg tablets
• Prescription status: Rx-only in most jurisdictions
• Mechanism: 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 oxypurinol: 18–30 hours
• Metabolism: Hepatic, to active metabolite oxypurinol
• Excretion: Primarily renal

Benefits

• Prevents the formation of new uric acid crystals in joints and soft tissues
• Reduces the frequency and severity of recurrent gout attacks over time
• Helps resolve existing tophi (urate crystal deposits) with sustained therapy
• Lowers the risk of uric acid nephrolithiasis (kidney stones)
• May prevent urate nephropathy in patients with chronic hyperuricemia
• Provides a prophylactic foundation for patients undergoing chemotherapy who are at risk for tumor lysis syndrome

Common use

Allopurinol is primarily indicated for the management of:

• Chronic gout and gouty arthritis
• Hyperuricemia secondary to malignancies (e.g., leukemias, lymphomas)
• Recurrent uric acid kidney stones
• Hyperuricemia associated with renal calculi
• Prophylaxis of acute uric acid nephropathy during cytotoxic therapy

It is not intended for the treatment of acute gout attacks and may initially exacerbate symptoms if initiated during an active flare.

Dosage and direction

Dosage must be individualized based on serum uric acid levels, renal function, and therapeutic response. The following represents general guidance:

Adults (gout/hyperuricemia):

• Initial dose: 100 mg once daily
• Maintenance dose: 200–300 mg daily for mild gout; 400–600 mg daily for moderate to severe gout
• Maximum dose: 800 mg daily (in divided doses if exceeding 300 mg)

Dosing in renal impairment:

• CrCl 10–20 mL/min: Max 200 mg daily
• CrCl 3–10 mL/min: Max 100 mg daily
• CrCl <3 mL/min: Dosing interval extended to every 48–72 hours

Administration:

• Take after meals to minimize gastric upset
• Maintain adequate hydration (2–3 L fluid daily unless contraindicated)
• Dose adjustments should occur at approximately weekly intervals based on uric acid levels
• Do not crush or chew tablets

Therapeutic effect is typically observed within 1–2 weeks, with optimal urate-lowering achieved after 2–6 weeks of continuous therapy.

Precautions

• Initiate therapy at lowest effective dose to minimize risk of acute gout flare
• Monitor renal function and hepatic enzymes periodically
• Screen for HLA-B*5801 allele prior to initiation in populations at higher risk for severe cutaneous reactions (e.g., Han Chinese, Korean, Thai)
• Use with caution in patients with pre-existing hepatic impairment
• May cause drowsiness; caution when operating machinery
• Periodic complete blood counts recommended during first few months of therapy
• Not recommended during pregnancy unless potential benefit justifies potential risk
• Excreted in breast milk; use during lactation requires risk-benefit assessment

Contraindications

• Hypersensitivity to allopurinol or any component of the formulation
• Patients who have experienced severe cutaneous reactions to allopurinol (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis)
• Asymptomatic hyperuricemia (except during cytotoxic therapy)
• Concurrent use with didanosine
• Severe hepatic impairment without close monitoring
• Children, except those with hyperuricemia secondary to malignancy

Possible side effect

Common (≥1%):

• Skin rash (discontinue immediately if rash occurs)
• Nausea, vomiting, diarrhea
• Elevated liver enzymes
• Drowsiness, headache
• Acute gout flare (especially during initiation)

Less common (<1%):

• Eosinophilia, leukopenia, thrombocytopenia
• Hepatotoxicity
• Peripheral neuropathy
• Alopecia
• Taste perversion

Rare but serious:

• Severe cutaneous adverse reactions (SCARs): Stevens-Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS)
• Vasculitis
• Renal failure
• Bone marrow suppression
• Hepatitis

Drug interaction

• Azathioprine/6-mercaptopurine: Allopurinol inhibits metabolism, requiring 65-75% dose reduction
• Warfarin: Enhanced anticoagulant effect; monitor INR closely
• Diuretics: May increase risk of hypersensitivity reactions
• Ampicillin/amoxicillin: Increased incidence of skin rash
• Theophylline: Reduced clearance; monitor levels
• Cyclophosphamide: Enhanced bone marrow suppression
• ACE inhibitors: Increased risk of hypersensitivity reactions
• Didanosine: Contraindicated due to increased toxicity

Missed dose

• If a dose is missed, take it as soon as remembered unless it is almost time for the next dose
• Do not double the dose to make up for a missed dose
• Maintain regular dosing schedule to ensure consistent uric acid suppression
• Contact healthcare provider if multiple doses are missed for guidance on restarting therapy

Overdose

Symptoms: Nausea, vomiting, diarrhea, dizziness, oliguria, hepatic dysfunction, acute renal failure.

Management:

• Gastric lavage if presentation is early
• Supportive care with maintenance of hydration and electrolyte balance
• Hemodialysis may be effective for removal of allopurinol and oxypurinol
• Monitor renal and hepatic function closely
• No specific antidote available

Storage

• Store at controlled room temperature (20–25°C/68–77°F)
• Protect from light and moisture
• Keep in original container with tight closure
• Do not store in bathroom or near sink
• Keep out of reach of children and pets
• Do not use after expiration date
• Dispose of unused medication properly according to local regulations

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Allopurinol is a prescription medication that should be used only under the supervision of a qualified healthcare professional. Dosage and treatment duration must be individualized based on medical history, renal function, and therapeutic response. Never initiate, adjust, or discontinue medication without consulting your physician. Report any adverse effects or concerns to your healthcare provider promptly.

Reviews

Clinical evidence consistently demonstrates allopurinol’s efficacy in maintaining serum uric acid levels below 6 mg/dL, the saturation point for urate crystals. Long-term studies show significant reduction in gout flare frequency (70-80% reduction after 1 year), resolution of tophi, and prevention of joint damage. The medication is generally well-tolerated with proper dosing and monitoring, though the risk of severe cutaneous reactions, while rare, necessitates careful patient selection and education. Renal function remains the primary consideration in dosing, with studies confirming the safety of appropriately adjusted regimens even in advanced CKD. The decades of clinical experience with allopurinol position it as a first-line urate-lowering therapy with a well-characterized risk-benefit profile.