Allopurinol exerts its therapeutic effects through its action on the enzyme xanthine oxidase. Its key mechanisms include:

1. Xanthine Oxidase Inhibition:
   • Allopurinol and its active metabolite, oxypurinol, inhibit the enzyme xanthine oxidase.
   • This enzyme is responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid.
   • By inhibiting xanthine oxidase, allopurinol reduces the production of uric acid, lowering its levels in the blood and urine.
2. Reduction of Uric Acid Formation:
   • Allopurinol decreases the formation of uric acid, preventing the deposition of urate crystals in joints and tissues, which is the underlying cause of gout.
3. Increase in Uric Acid Excretion:
   • By reducing uric acid production, allopurinol indirectly increases the excretion of uric acid, further lowering its levels in the body.

Allopurinol is approved for a variety of clinical conditions, including:

1. Gout:
   • Prevention of recurrent gout attacks and tophi (urate crystal deposits).
   • Management of chronic gouty arthritis.
2. Hyperuricemia:
   • Treatment of hyperuricemia associated with conditions such as Lesch-Nyhan syndrome and myeloproliferative disorders.
3. Chemotherapy-Induced Hyperuricemia:
   • Prevention of tumor lysis syndrome and hyperuricemia in patients undergoing chemotherapy for hematologic malignancies (e.g., leukemia, lymphoma).
4. Kidney Stones:
   • Prevention of uric acid kidney stones.
5. Off-Label Uses:
   • Treatment of calcium oxalate kidney stones (in combination with other therapies).

The dosage of allopurinol varies depending on the indication, patient response, and renal function. The following dosing guidelines are based on the British National Formulary (BNF) and clinical pharmacology references:

1. Gout and Hyperuricemia:
   • Adults: Start with 100 mg daily, increasing by 100 mg every 2–4 weeks to a maintenance dose of 100–300 mg daily. The maximum dose is 900 mg daily.
   • Elderly Patients: Lower starting doses (50–100 mg daily) and slower titration are recommended.
2. Chemotherapy-Induced Hyperuricemia:
   • Adults: 600–800 mg daily in divided doses for 2–3 days before and during chemotherapy.
3. Children:
   • Gout and Hyperuricemia: 10–20 mg/kg/day in divided doses, not exceeding 400 mg daily.
   • Chemotherapy-Induced Hyperuricemia: 200–400 mg/m²/day in divided doses.

Important Considerations:

• Allopurinol is available in oral tablets.
• Dose adjustments may be necessary for patients with renal impairment. The dose should be reduced in patients with a creatinine clearance (CrCl) of less than 30 mL/min.
• Adequate hydration is essential to prevent the formation of uric acid crystals in the urine.

Allopurinol is generally well-tolerated, but it is associated with a range of side effects, some of which can be serious. Common side effects include:

1. Gastrointestinal:
   • Nausea, vomiting, and diarrhea.
2. Dermatological:
   • Rash and pruritus (itching).
3. Other:
   • Headache and drowsiness.

Serious Side Effects:

• Hypersensitivity Reactions: Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS). These are rare but life-threatening conditions requiring immediate discontinuation of the drug.
• Hepatotoxicity: Elevated liver enzymes and, rarely, severe liver damage.
• Bone Marrow Suppression: Leukopenia, thrombocytopenia, and agranulocytosis (rare).

Allopurinol requires careful monitoring and adherence to specific precautions to ensure patient safety:

1. Hypersensitivity Reactions:
   • Patients should be advised to discontinue allopurinol and seek medical attention immediately if they develop a rash, fever, or other signs of hypersensitivity.
2. Renal Impairment:
   • Dose adjustments are necessary for patients with impaired kidney function. The dose should be reduced in patients with a creatinine clearance (CrCl) of less than 30 mL/min.
3. Pregnancy and Lactation:
   • Allopurinol should be used during pregnancy only if the potential benefits outweigh the risks. It is excreted in breast milk, so breastfeeding is generally not recommended.
4. Elderly Patients:
   • Lower doses may be required due to increased sensitivity to side effects, particularly renal impairment.
5. Hydration:
   • Adequate hydration is essential to prevent the formation of uric acid crystals in the urine.

Allopurinol has a significant potential for drug interactions due to its effects on xanthine oxidase and its metabolism. Key interactions include:

1. Azathioprine and Mercaptopurine:
   • Allopurinol inhibits the metabolism of these drugs, increasing their levels and the risk of toxicity. Dose reductions of azathioprine and mercaptopurine are necessary when used with allopurinol.
2. Warfarin:
   • Allopurinol may enhance the anticoagulant effects of warfarin, increasing the risk of bleeding.
3. Theophylline:
   • Allopurinol may increase the levels of theophylline, increasing the risk of side effects.
4. Ampicillin and Amoxicillin:
   • Allopurinol may increase the risk of rash when used with these antibiotics.
5. Diuretics:
   • Thiazide diuretics may increase the risk of hypersensitivity reactions when used with allopurinol.

Allopurinol is the generic name for this medication. It is marketed under various brand names, depending on the country and manufacturer. Some examples include:

• Zyloprim (a well-known brand in the United States and other regions).
• Allopurinol Accord.
• Allopurinol Mylan.
• Allopurinol Sandoz.