Allopurinol instructions for administration

Instructions for administration
Overview Serum urate levels Colchicine/anti-inflammatory agents Transferring patient from uricosuric agent Meals/fluid intake Renal failure Serum uric acid level Uric acid nephropathy Calcium oxalate stones Children 6 to 10 years of age with secondary hyperuricemia

Overview
The dosage of Allopurinol to accomplish full control of gout and to lower serum uric acid to normal or near-normal levels varies with the severity of the disease. The average is 200 to 300 mg per day for patients with mild gout and 400 to 600 mg per day for those with moderately severe tophaceous gout. The appropriate dosage may be administered in divided doses or as a single equivalent dose with the 300 mg tablet. Dosage requirements in excess of 300 mg should be administered in divided doses. The minimal effective dosage is 100 to 200 mg daily and the maximal recommended dosage is 800 mg daily. To reduce the possibility of flare-up of acute gouty attacks, it is recommended that the patient start with a low dose of Allopurinol (100 mg daily) and increase at weekly intervals by 100 mg until a serum uric acid level of 6 mg/dL or less is attained but without exceeding the maximal recommended dosage. Return to top

Serum urate levels
Normal serum urate levels are usually achieved in one to three weeks. The upper limit of normal is about 7 mg/dL for men and postmenopausal women and 6 mg/dL for premenopausal women. Too much reliance should not be placed on a single serum uric acid determination since, for technical reasons, estimation of uric acid may be difficult. By selecting the appropriate dosage and, in certain patients, using uricosuric agents concurrently, it is possible to reduce serum uric acid to normal or, if desired, to as low as 2 to 3 mg/dL and keep it there indefinitely. Return to top

Colchicine/anti-inflammatory agents
While adjusting the dosage of Allopurinol in patients who are being treated with colchicine and/or anti-inflammatory agents, it is wise to continue the latter therapy until serum uric acid has been normalized and there has been freedom from acute gouty attacks for several months. Return to top

Transferring patient from uricosuric agent
In transferring a patient from a uricosuric agent to Allopurinol, the dose of the uricosuric agent should be gradually reduced over a period of several weeks and the dose of Allopurinol gradually increased to the required dose needed to maintain a normal serum uric acid level. Return to top

Meals/fluid intake
It should also be noted that Allopurinol is generally better tolerated if taken following meals. A fluid intake sufficient to yield a daily urinary output of at least 2 liters and the maintenance of a neutral or, preferably, slightly alkaline urine are desirable. Return to top

Renal failure
Since Allopurinol and its metabolites are primarily eliminated only by the kidney, accumulation of the drug can occur in renal failure, and the dose of Allopurinol should consequently be reduced. With a creatinine clearance of 10 to 20 mL/min, a daily dosage of 200 mg of Allopurinol is suitable. When the creatinine clearance is less than 10 mL/min the daily dosage should not exceed 100 mg. With extreme renal impairment (creatinine clearance less than 3 mL/min) the interval between doses may also need to be lengthened. Return to top

Serum uric acid level
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 level as an index. Return to top

Uric acid nephropathy
For the prevention of uric acid nephropathy during the vigorous therapy of neoplastic disease, treatment with 600 to 800 mg daily for two or three days is advisable together with a high fluid intake. Otherwise similar considerations to the above recommendations for treating patients with gout govern the regulation of dosage for maintenance purposes in secondary hyperuricemia. Return to top

Calcium oxalate stones
The dose of Allopurinol recommended for management of recurrent calcium oxalate stones in hyperuricosuric patients is 200 to 300 mg/day in divided doses or as the single equivalent. This dose may be adjusted up or down depending upon the resultant control of the hyperuricosuria based upon subsequent 24 hour urinary urate determinations. Clinical experience suggests that patients with recurrent calcium oxalate stones may also benefit from dietary changes such as the reduction of animal protein, sodium, refined sugars, oxalate-rich foods, and excessive calcium intake as well as an increase in oral fluids and dietary fiber. Return to top

Children 6 to 10 years of age with secondary hyperuricemia
Children, 6 to 10 years of age, with secondary hyperuricemia associated with malignancies may be given 300 mg Allopurinol daily while those under 6 years are generally given 150 mg daily. The response is evaluated after approximately 48 hours of therapy and a dosage adjustment is made if necessary. Return to top