ZYTOL ( TABLET, DISPERSIBLE )

• Prophylaxis of gout
• Prophylaxis of hyperuricaemia associated with cancer chemotherapy.

Source : IAP Pediatric Drug Formulary
Hyperuricemia due to tumor lysis syndrome: IV/ oral 100mg/sq m 3 times daily be commenced 24 hours before starting cytotoxic drugs. GSD and MMA: 10-15 mg/kg (maximum 400gm) as single daily dose if serum uric acid > 0.36 mmol/L. PRPP synthetase superactivity and Lesch-Nyhan syndrome: 10-20mg/kg (maximum 400mg) daily once at mimimum dose to maintain normal uric acid levels. APRT deficiency: 10mg/kg (maximum 400mg).

Source : NFI National Formulary of India
Oral

• Adult- Initially 100 mg daily after food,thereafter adjust according to uric acidconcentration. (Usual maintenance dosein mild conditions: 100 to 200 mg daily, inmoderately severe condition: 300 mg dailygiven in divided doses).
• Child- Neoplastic conditions and enzymedisorders: 10 to 20 mg/kg daily (max. 400 mg).

• Acute gout
• if an acute attack occurs while receiving allopurinol
• Continue prophylaxis and treat attack separately.
• Do not start during acute gout. Does not prevent neurological features of Lesch-Nyhan syndrome. Increased risk of toxicity (e.g., rashes) in hepatic and renal failure, Reduce dose in renal and hepatic failure. A high fluid intake and low purine diet are recommended in APRT deficiency, PRPP synthetase superactivity and  Lesch-Nyhan syndrome, with urinary alkalinisation in the latter two.

• Ensure adequate fluid intake of 2-3 litres daily
• Lactation
• Renal and hepatic impairment
• Withdraw treatment if rash occurs
• Reintroduce if rash is mild but discontinue immediately if it recurs
• Interactions
• Pregnancy

• Rash (see precautions above)
• Hypersensitivity reactions occur rarely, and include fever
• Lymphadenopathy
• Arthralgia
• Eosinophilia
• Erythema multiforme (Stevens-Johnson syndrome) or toxic epidermal necrolysis
• Vasculitis
• Hepatitis
• Renal impairment
• Withdraw treatment if rash develops; if mild, reintroduce cautiously but discontinue immediately if reappears. Hypersensitivity reactions (rare) include exfoliation, fever, lymphadenopathy, arthralgiam eosinophilia and vasculitis. gastrointestinal disorders. Rerely headaches, drowsiness, visual or taste disturbance, neuropathy, aalopecia, hepatotoxicity or blood disorders.

Bioavailability varies from 67-90%. Peak plasma levels of allopurinol generally occur approximately 1.5 hours after oral administration. Allopurinol is negligibly bound by plasma proteins. Elimination of allopurinol is mainly by metabolic conversion to oxipurinol by xanthine oxidase and aldehyde oxidase, with less than 10% of the unchanged drug excreted in urine.

Allopurinol and its main metabolite (oxipurinol) lower the level of uric acid by inhibition of xanthineoxidase, the enzyme catalyzing the oxidation of hypoxanthine to xanthine and xanthine to uric acid. In addition, de novo purine biosynthesis is depressed via feedback inhibition of hypoxanthine-guanine phosphoribosyltransferase.

Toxicity not reported but drug is avoided if posible.

Allopurinol enters breast milk.

Risk of toxicity increased by captopril. especially in renal impairment. Increased toxicity of azathioprine or in mercaptopurine: reduce dose of these warfarn, acenocoumaraol and cyclosporin.

Massive inhibition of xanthine oxidase activity - no untoward effect unless affection concomitant medication, especially with axathioprine or mercaptopurine. Adequate hydration facilitates excretion of allopurinol and its metabolites. If considered necessary hemodialysis may be used.