Dosage range of 100 to 800 mg daily divided into 1 to 3 doses. Single dose should not exceed 300 mg. Allopurinol is better tolerated when taken with meals.
In all patients receiving allopurinol, a high fluid intake (e.g 2.5 to 3 litres) and the maintenance of a neutral or, preferably, slightly alkaline urine are recommended.
The dose of allopurinol varies with the severity of the disease and should be adjusted according to the response and tolerance of the patient. Some investigators have reported an increase in acute attacks of gout during the early stages of allopurinol administration. Accordingly, the patient should start with a low dose of allopurinol (100 to 200 mg/day) and increase at weekly intervals by 100 mg until a serum uric acid concentration of about 360 μmol/L (6 mg%) or less is attained or until the maximum recommended dosage of 800 mg/day (in patients with normal renal function) is reached. Also a maintenance dose of colchicine (0.6 mg twice daily) or a nonsteroidal anti-inflammatory drug should be given prophylatically when allopurinol is begun. After serum urate concentrations are controlled, it may be possible to reduce dosage; the minimum effective dose of allopurinol is 100 to 200 mg/day. The average maintenance dosage is 200 to 300 mg/day for patients with mild gout, 400 to 600 mg/day for patients with moderately severe tophaceous gout, and 700 to 800 mg/day in severe conditions.
Dosage in renal impairment:
Since allopurinol and its metabolites are excreted only by the kidney, drug accumulation can occur in renal failure and the initial dose of allopurinol should consequently be reduced. With a creatinine clearance of 0.33 to 0.17 mL/s (20 to 10 mL/min), a daily dosage of 200 mg of allopurinol is suitable. When the creatinine clearance is less than 0.17 mL/s (10 mL/min) the daily dosage should not exceed 100 mg. With extreme renal impairment (creatinine clearance less than 0.05 mL/s (3 mL/min), the interval between doses may also need to be lengthened. Some clinicians recommend the following maintenance dosages of allopurinol based on the patient’s creatinine clearance. (See table.)
Click on icon to see table/diagram/image
As no simple method of measuring allopurinol's blood concentrations is available, the correct size and frequency of dosage for maintaining the serum uric acid just within the normal range is best determined by using the serum uric acid concentration as an index.
Once the daily dose of allopurinol necessary to produce the desired serum uric acid concentration has been determined, continue this dose until serum uric acid concentration indicates a need for dosage adjustment.
Normal serum urate concentrations are achieved in 1 to 3 weeks. The upper limit of normal is about 360 μmol/L (6 mg%) for men and postmenopausal women and 300 μmol/L (5 mg%) for premenopausal women. By the selection of the appropriate dose, together with the use of uricosuric agents in certain patients, it is possible to reduce serum uric acid concentration to normal and, if desired, to hold it as low as 120 to 180 μmol/L (2 to 3 mg%). Combined therapy of allopurinol and uricosurics will often result in a dosage reduction of both agents.
In patients who are being treated with uricosuric agents colchicine and/or anti-inflammatory agents. It is wise to continue this therapy while adjusting the allopurinol dosage until a normal serum uric acid concentration and freedom from acute attacks have been maintained for several months. If desired, the patient may then be transferred to allopurinol therapy exclusively. When a uricosuric agent is being withdrawn, dosage of the uricosuric agent should be gradually reduced over several weeks.
Prevention of Uric Acid Nephropathy during the Vigorous Therapy of Neoplastic Disease:
Treatment with 600 to 800 mg daily for 2 to 3 days prior to chemotherapy or irradiation is advisable. When allopurinol is used with mercaptopurine or azathioprine, dosage of the latter drugs must be reduced (See Warnings). Continue treatment at a dosage adjusted to serum uric acid concentration until there is no longer a threat of hyperuricemia and hyperuricosuria. Allopurinol treatment can be maintained during the antimitotic therapy for prophylaxis of the hyperuricemia which may arise during the natural crises of the disease. In prolonged treatment, 300 to 400 mg of allopurinol daily is usually enough to control the serum uric acid concentration.
Prophylaxis of Renal Calcium Lithiasis:
200 to 300 mg daily therapy should be continued indefinitely. Some patients have received maintenance doses of 200 to 300 mg daily for more than 7 years. In some patients, the maintenance dose may be reduced to 100 to 200 mg daily.
For the treatment of secondary hyperuricemia associated with malignancies. (6 to 10 years of age):
give 300 mg of allopurinol daily; (<6 years of age):
give 150 mg of allopurinol daily; In Lesch-Nyhan syndrome (6 to 10 years of age):
give allopurinol in doses of 10 mg/kg/day. Evaluate the response after approximately 48 hours by monitoring serum uric acid and/or urinary uric acid concentrations and adjust the dose if necessary.