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

1. Xanthine Oxidase Inhibition:
   • Febuxostat is a selective and potent inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid.
   • By inhibiting xanthine oxidase, febuxostat reduces the production of uric acid, lowering its levels in the blood and urine.
2. Reduction of Uric Acid Formation:
   • Febuxostat 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, febuxostat indirectly increases the excretion of uric acid, further lowering its levels in the body.

Febuxostat is approved for specific clinical conditions, including:

1. Gout:
   • Management of chronic gout in patients with hyperuricemia.
   • Prevention of gout flares and tophi (urate crystal deposits).
2. Hyperuricemia:
   • Treatment of hyperuricemia associated with conditions such as Lesch-Nyhan syndrome and myeloproliferative disorders.
3. Off-Label Uses:
   • Prevention of tumor lysis syndrome in patients undergoing chemotherapy for hematologic malignancies (e.g., leukemia, lymphoma).

The dosage of febuxostat 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 80 mg once daily, increasing to 120 mg once daily if serum uric acid levels are not adequately controlled after 2–4 weeks.
   • Elderly Patients: No dose adjustment is required, but caution is advised due to potential comorbidities.
2. Renal Impairment:
   • No dose adjustment is required for patients with mild to moderate renal impairment (CrCl ≥30 mL/min). Use with caution in severe renal impairment (CrCl <30 mL/min).
3. Hepatic Impairment:
   • No dose adjustment is required for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment.

Important Considerations:

• Febuxostat is available in oral tablets.
• Adequate hydration is essential to prevent the formation of uric acid crystals in the urine.
• Prophylaxis with colchicine or NSAIDs is recommended during the initial months of febuxostat therapy to prevent gout flares.

Febuxostat 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, diarrhea, and abdominal pain.
2. Hepatic:
   • Elevated liver enzymes.
3. Other:
   • Headache and rash.

Serious Side Effects:

• Cardiovascular Events: Increased risk of cardiovascular events, including myocardial infarction and stroke.
• Hypersensitivity Reactions: Stevens-Johnson syndrome (SJS) and drug rash with eosinophilia and systemic symptoms (DRESS). These are rare but life-threatening conditions requiring immediate discontinuation of the drug.
• Hepatotoxicity: Severe liver damage (rare).

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

1. Cardiovascular Risk:
   • Use with caution in patients with a history of cardiovascular disease. Regular monitoring of cardiovascular health is recommended.
2. Hepatic Monitoring:
   • Regular monitoring of liver function tests is essential, particularly during the first 6 months of treatment.
3. Pregnancy and Lactation:
   • Febuxostat 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:
   • No dose adjustment is required, but caution is advised due to potential comorbidities and increased sensitivity to side effects.
5. Gout Flares:
   • Prophylaxis with colchicine or NSAIDs is recommended during the initial months of febuxostat therapy to prevent gout flares.

Febuxostat has a moderate potential for drug interactions due to its metabolism via hepatic enzymes. Key interactions include:

1. Azathioprine and Mercaptopurine:
   • Febuxostat inhibits the metabolism of these drugs, increasing their levels and the risk of toxicity. Concurrent use is contraindicated.
2. Theophylline:
   • Febuxostat may increase the levels of theophylline, increasing the risk of side effects.
3. Warfarin:
   • Febuxostat may enhance the anticoagulant effects of warfarin, increasing the risk of bleeding.
4. Other Interactions:
   • NSAIDs: Increased risk of gastrointestinal side effects.
   • Diuretics: May increase the risk of hyperuricemia.

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

• Adenuric (a well-known brand in the United Kingdom and other regions).
• Uloric (a well-known brand in the United States and other regions).
• Febuxostat Accord.
• Febuxostat Mylan.