Allopurinol: Effective Uric Acid Control for Gout Management
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Synonyms
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Allopurinol is a xanthine oxidase inhibitor prescribed primarily for the long-term management of hyperuricemia, the underlying cause of gout. By reducing the production of uric acid in the body, it helps prevent the formation of urate crystals, which are responsible for the painful inflammation and joint damage characteristic of gout. This medication is a cornerstone in prophylactic therapy, offering a systematic approach to controlling serum urate levels and reducing the frequency and severity of gout attacks. It is also used in the management of uric acid nephropathy and during chemotherapy to prevent tumor lysis syndrome.
Features
- Active ingredient: Allopurinol
- Drug class: Xanthine oxidase inhibitor
- Available forms: Oral tablets (100 mg and 300 mg)
- Prescription-only medication
- Generic availability: Yes
- Mechanism: Inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid
Benefits
- Reduces the frequency and intensity of acute gout attacks over time
- Prevents the formation of tophi (urate crystal deposits) and joint damage
- Lowers serum uric acid levels to below the saturation point for crystal formation
- Decreases the risk of uric acid kidney stone formation
- Provides long-term management of hyperuricemia with once-daily dosing in most cases
- May help preserve renal function in patients with uric acid nephropathy
Common use
Allopurinol is primarily indicated for the management of:
- Chronic gout and gouty arthritis
- Hyperuricemia secondary to malignancies (during chemotherapy or radiation)
- Recurrent uric acid stone formation
- Prophylaxis of uric acid nephropathy in patients with neoplastic disease
It is not intended for the treatment of acute gout attacks, as initiation of therapy may precipitate an acute episode. Rather, it is used as a long-term prophylactic agent to manage underlying hyperuricemia.
Dosage and direction
Dosage must be individualized based on serum uric acid levels, renal function, and the indication for treatment. The following represents general guidance:
Initial dose: Typically 100 mg once daily, with weekly increments of 100 mg until desired uric acid levels are achieved (usually below 6 mg/dL) Maintenance dose: 200-300 mg daily for mild gout; 400-600 mg daily for moderate to severe gout; maximum dose 800 mg daily Dosing in renal impairment: Requires adjustment based on creatinine clearance:
- CrCl 10-20 mL/min: Max 200 mg daily
- CrCl 3-10 mL/min: Max 100 mg daily
- CrCl <3 mL/min: Interval extension to every 48 hours or longer
Administration should be with food or milk to minimize gastric upset. Adequate fluid intake (2-3 liters daily) is recommended to maintain neutral or slightly alkaline urine and prevent renal stone formation.
Precautions
- Initiate therapy at low doses to minimize risk of acute gout flare (prophylactic NSAIDs or colchicine may be used during first 3-6 months)
- Monitor renal function and hepatic enzymes periodically during treatment
- Perform complete blood counts periodically, especially during first few months of therapy
- Use with caution in patients with history of hepatic disease or bone marrow suppression
- May cause drowsiness or dizziness; caution patients about driving or operating machinery
- Skin reactions require immediate medical attention as they may indicate serious hypersensitivity
Contraindications
Allopurinol is contraindicated in patients with:
- History of severe hypersensitivity reaction to allopurinol or any component of the formulation
- Asymptomatic hyperuricemia (except during chemotherapy for malignancy)
- Concurrent use with didanosine (increased toxicity risk)
- Severe hepatic impairment or active liver disease
- History of allopurinol-induced severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
Possible side effect
Common side effects (≥1%):
- Skin rash (discontinue immediately if rash occurs)
- Nausea, vomiting, diarrhea
- Drowsiness, headache
- Elevated liver enzymes
Less common but serious side effects:
- Severe skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis)
- Hepatotoxicity (jaundice, dark urine, abdominal pain)
- Bone marrow suppression (leukopenia, thrombocytopenia, agranulocytosis)
- Allopurinol hypersensitivity syndrome (fever, eosinophilia, rash, hepatitis, renal impairment)
- Vasculitis, peripheral neuropathy
Drug interaction
Significant interactions include:
- Azathioprine/6-mercaptopurine: Allopurinol inhibits their metabolism, increasing toxicity (dose reduction of 65-75% required)
- Warfarin: Enhanced anticoagulant effect; monitor INR closely
- Diuretics (especially thiazides): May decrease allopurinol efficacy and increase risk of hypersensitivity
- Ampicillin/amoxicillin: Increased incidence of skin rash
- Theophylline: Increased serum levels of theophylline
- Cyclophosphamide: Enhanced bone marrow suppression
- ACE inhibitors: Increased risk of hypersensitivity reactions
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 one. Maintain regular dosing schedule to ensure consistent uric acid control.
Overdose
Symptoms may include nausea, vomiting, diarrhea, and dizziness. In severe cases, acute renal failure may occur. Management is supportive and includes gastric lavage if presented early, adequate hydration, and monitoring of renal function. Hemodialysis may be effective in removing allopurinol and its active metabolite.
Storage
Store at room temperature (15-30°C/59-86°F) in a tight, light-resistant container. Keep away from moisture and heat. Do not store in bathroom. 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 or changing any medication regimen. Dosage and treatment decisions should be made based on individual patient characteristics and under medical supervision. The prescriber should be familiar with the complete prescribing information before administering allopurinol.
Reviews
Clinical studies demonstrate that allopurinol effectively reduces serum urate levels in approximately 80-90% of patients with chronic gout when appropriate doses are used. The medication shows particular efficacy in preventing recurrent gout attacks, with studies showing a 70-80% reduction in acute episodes after 6-12 months of consistent therapy. Renal function preservation in hyperuricemic patients has been demonstrated in multiple long-term studies. The tolerability profile is generally favorable, though hypersensitivity reactions remain a concern requiring careful patient selection and monitoring.