Primary & secondary gout.
Xanthine Oxidase Inhibitor; Antigout
Allopurinol is a xanthine oxidase inhibitor which is administered orally. It acts on purine catabolism without disrupting the biosynthesis of purines. It reduces the production of uric acid by inhibiting the biochemical reactions immediately preceding its formation. Allopurinol is a structural analogue of the natural purine base, hypoxanthine. It is an inhibitor of xanthine oxidase, the enzyme responsible for the conversion of hypoxanthine to xanthine and xanthine to uric acid, the end product of purine metabolism. Allopurinol is approximately 90% absorbed from the GI tract. Peak plasma levels generally occur at 1.5 hours to 4.5 hours. It has a plasma half life of about 1 to 2 hours. Approximately 20% of the ingested Allopurinol is excreted in the faeces.
Allopurinol should be introduced at low dosage e.g. 100mg/day to reduce the risk of adverse reactions & increased only if the serum urate response is unsatisfactory. Extra caution should be exercised if renal function is poor. The following dosage schedules are suggested: • 100 to 200 mg daily in mild conditions, • 300 to 600 mg daily in moderately severe conditions, • 700 to 900 mg daily in severe conditions. If dosage on a mg/kg body weight basis is required, 2 to 10 mg/kg body weight per day should be used. Dosage in Children: Children under 15 years: 10 to 20 mg/kg body weight per day up to a maximum of 400 mg daily. Dosage in the elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used. Dosage in renal impairment: In severe renal insufficiency, it may be advisable to use less than 100 mg /day or to use single doses of 100 mg at longer intervals than one day.
When 6-mercaptopurine or azathioprine is given concurrently with Allopurinol, only one-quarter of the usual dose of 6- mercaptopurine or azathioprine should be given because inhibition of xanthine oxidase will prolong their activity. Evidence suggests that the plasma half-life of vidarabine is increased in the presence of allopurinol. When the two products are used concomitantly extra vigilance is necessary, to recognise enhanced toxic effects. Theophylline levels should be monitored in patients starting or increasing allopurinol therapy. An increase in frequency of skin rash has been reported among patients receiving ampicillin or amoxicillin concurrently with allopurinol compared to patients who are not receiving both drugs. Reports suggest that the plasma concentration of ciclosporin may be increased during concomitant treatment with allopurinol.
Hypersensitivity; acute attack of gout. Ensure adequate fluid intake. Prophylactically w/ an anti-inflammatory or colchicine for at least 1 mth. Withdraw immediately when sensitivity (skin rash, etc) appears. Pregnancy, lactation. Hepatic & renal impairment.
Pruritic maculopapular skin eruptions, fever, chill, arthralgias, cholestatic jaundice, eosinophilia & mild leukocytosis or leukopenia.
This drug should be used during pregnancy only if clearly indicated, caution should be exercised when Allopurinol is administered to a lactating mother.
Ingestion of up to 22.5 g allopurinol without adverse effect has been reported. Symptoms and signs including nausea, vomiting, diarrhoea and dizziness have been reported in a patient who ingested 20 gm allopurinol. Adequate hydration to maintain optimum diuresis facilitates excretion of allopurinol and its metabolites. If considered necessary haemodialysis may be used.
Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.
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