Esloric

• Approved Indications:
• Gout: Prevention of gout attacks by lowering serum uric acid levels.
• Hyperuricemia: Secondary to chemotherapy or malignancies causing tumor lysis syndrome.
• Recurrent Calcium Oxalate Nephrolithiasis: Where hyperuricosuria is a contributing factor.
• Uric Acid Nephropathy: To prevent uric acid deposition in kidneys.
• Certain Enzyme Disorders: Such as Lesch-Nyhan syndrome and other purine metabolism disorders.
• Off-label/Clinically Accepted Uses:
• Prevention of hyperuricemia in organ transplant patients.
• Management of chronic tophaceous gout.

• Adults:
• Initial dose: 100 mg daily, titrated up every 1–2 weeks based on serum uric acid levels.
• Maintenance dose: 200–300 mg daily; some patients may require up to 800 mg daily divided doses.
• For tumor lysis syndrome prophylaxis: 600–800 mg daily in divided doses.
• Elderly: Same dosing as adults; start low and titrate cautiously.
• Pediatrics:
• Dose individualized based on body weight and clinical condition, usually 10 mg/kg/day in divided doses.
• Renal Impairment:
• Dose adjustment necessary; reduce dose and/or extend dosing interval based on creatinine clearance.
• Example: For CrCl <20 mL/min, initial dose may be 50 mg daily or every other day.
• Hepatic Impairment: No specific adjustment; monitor closely.
• Administration: Oral route preferred. Tablets swallowed whole with water after meals.

Allopurinol is a structural analog of hypoxanthine that inhibits xanthine oxidase, the enzyme responsible for converting hypoxanthine to xanthine and xanthine to uric acid. By inhibiting xanthine oxidase, allopurinol decreases production of uric acid, thereby lowering serum and urinary uric acid levels. This reduction prevents the formation and deposition of urate crystals, alleviating gout symptoms and reducing risk of uric acid nephropathy.

• Absorption: Rapid and almost complete oral absorption (~80–90%).
• Distribution: Widely distributed in body tissues; volume of distribution ~1.6 L/kg.
• Metabolism: Metabolized mainly in the liver to oxypurinol (alloxanthine), an active metabolite with a longer half-life.
• Half-life:
• Allopurinol: 1–2 hours.
• Oxypurinol: 15–30 hours, allowing once-daily dosing.
• Elimination: Primarily renal excretion of oxypurinol; dose adjustment needed in renal impairment.

• Pregnancy: Category C. Animal studies have shown adverse effects; human data limited. Use only if potential benefit justifies risk.
• Lactation: Excreted in breast milk in small amounts; use caution during breastfeeding.

• Primary Class: Antihyperuricemic agent
• Subclass: Xanthine oxidase inhibitor

• Hypersensitivity to allopurinol or any formulation components.
• History of allopurinol hypersensitivity syndrome or severe cutaneous adverse reactions (SCAR).
• Coadministration with didanosine (increased toxicity risk).
• Severe renal or hepatic impairment without appropriate monitoring.

• Severe cutaneous adverse reactions (SCAR): Stevens-Johnson syndrome, toxic epidermal necrolysis; discontinue immediately if rash develops.
• Hypersensitivity syndrome: Fever, rash, eosinophilia, hepatitis, renal failure; requires immediate cessation and supportive care.
• Renal impairment: Dose adjust and monitor renal function closely.
• Hepatic impairment: Monitor liver enzymes regularly.
• Use caution in patients with cardiovascular disease and gout flare risk: Initiate prophylaxis for gout attacks during early therapy with NSAIDs or colchicine.
• HLA-B*5801 allele: Increased risk of severe hypersensitivity in certain populations (e.g., Han Chinese, Thai, Korean); genetic testing may be advised in high-risk groups.

• Common: Rash, gastrointestinal upset (nausea, diarrhea), elevated liver enzymes.
• Less Common: Drowsiness, headache, acute gout attacks upon initiation, leukopenia.
• Serious/Rare: Severe hypersensitivity reactions (SCAR), hepatotoxicity, bone marrow suppression, interstitial nephritis.

• Azathioprine and mercaptopurine: Increased toxicity risk due to decreased metabolism; reduce dose of these agents if combined.
• Warfarin: Possible enhanced anticoagulant effect; monitor INR closely.
• Theophylline: Increased theophylline levels; monitor for toxicity.
• Ampicillin/amoxicillin: Increased risk of rash when combined.
• Didanosine: Contraindicated combination.
• Thiazide diuretics: Increased risk of hypersensitivity.
• Metabolized via xanthine oxidase; no major CYP450 involvement.

• Updated gout management guidelines emphasize early initiation of urate-lowering therapy with allopurinol, individualized dosing, and monitoring of serum uric acid to target <6 mg/dL.
• Genetic screening for HLA-B*5801 allele recommended in at-risk ethnicities before starting therapy.
• Safety alerts emphasize vigilance for hypersensitivity syndrome and need for early detection.

• Store at 20°C to 25°C (68°F to 77°F).
• Protect from moisture and light.
• Keep container tightly closed.
• Do not freeze.
• Keep out of reach of children.