Zyloric Dosage/Direction for Use

General: The dosage should be adjusted by monitoring serum urate concentrations and urinary urate/uric acid levels at appropriate intervals.
Allopurinol may be taken orally once a day after a meal. It is well tolerated, especially after food. Should the daily dosage exceed 300 mg and gastrointestinal intolerance be manifested, a divided dose regimen may be appropriate.
Populations: Adults: Allopurinol should be introduced at low dosage e.g. 100 mg/day to reduce the risk of adverse reactions and increased only if the serum urate response is unsatisfactory. Extra caution should be exercised if renal function is poor (see Renal impairment in the following text and Precautions).
The following dosage schedules are suggested: 100 to 200 mg daily in mild conditions; 300 to 600 mg daily in moderately severe conditions.
If dosage on a mg/kg bodyweight basis is required, 2 to 10 mg/kg bodyweight/day should be used.
Paediatric population (under 15 years): 100-300 mg daily, the response should be seen after 48 hours of treatment and dosage is adjusted if necessary. Use in children is rarely indicated, except in malignant conditions (especially leukaemia) and certain enzyme disorders such as Lesch-Nyhan syndrome.
Elderly: In the absence of specific data, the lowest dosage which produces satisfactory urate reduction should be used.
Particular attention should be paid to advice in Renal Impairment in the text as follows and Precautions.
Renal Impairment: Since allopurinol and its metabolites are excreted by the kidney, impaired renal function may lead to retention of the drug and/or its metabolites with consequent prolongation of plasma half-lives. In renal insufficiency, it is needed to take a serious consideration in starting treatment with 100 mg/day as maximum dose and increase it only if there is unsatisfaction on uric acid serum concentration. In severe renal insufficiency, it may be advisable to use less than 100 mg per day or to use single doses of 100 mg at longer intervals than one day.
If facilities are available to monitor plasma oxipurinol concentrations, the dose should be adjusted to maintain plasma oxipurinol levels below 100 micromol/litre (15.2 mg/litre).
Allopurinol and its metabolites are removed by renal dialysis. If dialysis is required two to three times a week, consideration should be given to an alternative dosage schedule of 300 to 400 mg allopurinol immediately after each dialysis with none in the interim.
Hepatic Impairment: Reduced doses should be used in patients with hepatic impairment.
Periodic liver function tests are recommended during the early stages of therapy.
Treatment of high urate turnover conditions e.g. neoplasia, Lesch-Nyhan syndrome: It is advisable to correct existing hyperuricaemia and/or hyperuricosuria with allopurinol before starting cytotoxic therapy. Adequate hydration is important to maintain optimum diuresis and alkalinisation of the urine is advisable to increase solubility of urinary urate/uric acid. Dosage of allopurinol should be at the lower end of the recommended dosage schedule.
If urate nephropathy or other pathology has compromised renal function, the advice given in Renal Impairment in the previous text should be followed. These steps may reduce the risk of xanthine and/or oxipurinol deposition complicating the clinical situation (see Interactions and Adverse Reactions).