Allopurinol Dosage

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Usual Adult Dose for Gout

Initial: 100 mg orally once a day.
Maintenance: 200 to 300 mg (mild gout) orally once a day or 400 to 600 mg/day (moderately severe tophaceous gout) in divided doses.

Usual Adult Dose for Hyperuricemia Secondary to Chemotherapy

Initial:
Parenteral: 200 to 400 mg/m2/day to a maximum of 600 mg/day
Oral: 600 to 800 mg/day for 1 to 3 days with consumption of at least 2 L of fluid/day.

Maintenance:
200 to 300 mg/day orally until patient no longer at high risk for developing hyperuricemia.

Usual Adult Dose for Calcium Oxalate Calculi with Hyperuricosuria

Initial: 200 to 300 mg orally once a day.
Maintenance: 300 mg/day or less.

Usual Adult Dose for Congestive Heart Failure

Study (n=11) to prevent the formation of superoxide free radicals and improve endothelial function (in NYHA class II to III chronic heart failure): 300 mg orally daily for 1 month

Usual Adult Dose for Cardiothoracic Surgery

Studies: Coronary Artery Bypass Graft Surgery
600 mg orally one day prior to surgery and another 600 mg orally the day of surgery.

Usual Adult Dose for Leishmaniasis

Study (n=31 - Cutaneous leishmaniasis: 20 mg/kg/day plus low-dose meglumine antimoniate (30 mg/kg/day) for 20 days.

Case Reports - Visceral leishmaniasis, post renal transplant: 300 mg daily plus meglumine antimoniate (50 mg/kg/day)

Usual Adult Dose for Mania

Case Reports -- Mania (bipolar I) associated with hyperuricemia: 300 mg orally daily.

Usual Adult Dose for High Risk Percutaneous Transluminal Angioplasty

Study (n=38) - Primary Percutaneous Transluminal Coronary Angioplasty (PTCA):
400 mg orally administered immediately after admission to the emergency department (approximately 60 minutes before reperfusion) and after primary PTCA was completed.

Usual Adult Dose for Reactive Perforating Collangenosis

Case Report: 100 mg orally daily.

Usual Pediatric Dose for Hyperuricemia Secondary to Chemotherapy

Parenteral :
Less than or equal to 10 years: 200 mg/m2/day in 1 to 3 equally divided doses not to exceed 600 mg/24 hours. All doses greater than 300 mg should be given in equally divided doses.
Greater than 10 years: 200 to 400 mg/m2/day administered in 1 to 3 equally divided doses, not to exceed 600 mg/24 hours.

Oral:
Less than 6 years: 150 mg/day orally in 3 divided doses.
6 to 10 years: 300 mg/day orally in 2 to 3 divided doses.
Greater than 10 years: 600 to 800 mg/day in 2 to 3 equally divided doses

Usual Pediatric Dose for Leishmaniasis

Greater than 5 years old
Study (n=31) - Cutaneous leishmaniasis: 20 mg/kg/day plus low-dose meglumine antimoniate (30 mg/kg/day) for 20 days.

Renal Dose Adjustments

Parenteral:
CrCl less than 3 mL/min: 100 mg/day at extended intervals
CrCl 3 to 10 mL/min: 100 mg/day
CrCl 10 to 20 mL/min: 200 mg/day

Oral:
CrCl less than 10 mL/min: 100 mg orally three times per week.
CrCl 10 mL/min: 100 mg orally on alternate days.
CrCl 20 mL/min: 100 mg orally once a day.
CrCl 40 mL/min: 150 mg orally once a day.
CrCl 60 mL/min: 200 mg orally once a day.

Liver Dose Adjustments

Data not available

Dose Adjustments

For treating gout, the dose should be titrated at weekly intervals to achieve the desired clinical response, typically a serum uric acid level of 6 mg/dl or less. Normal serum urate levels are usually achieved in 1 to 3 weeks. Doses greater than 300 mg/day should be given in divided doses.

Allopurinol for injection in combination therapy with mercaptopurine or azathioprine will require dose reductions of one-third to one-fourth the usual dose of mercaptopurine or azathioprine.

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.

Precautions

Allopurinol should be discontinued at the first sign of skin rash or any other signs or symptoms suggestive of a hypersensitivity reaction. In some instances, a skin rash may be followed by more severe adverse reactions such as exfoliative, urticarial, and purpuric lesions, as well as Stevens-Johnson syndrome (erythema multiforme exudativum), and/or generalized vasculitis, irreversible hepatotoxicity, and, rarely, death. Renal dysfunction increases the risk of allopurinol hypersensitivity.

A few cases of reversible clinical hepatotoxicity have been observed in patients administered allopurinol, and in some patients, asymptomatic rises in serum alkaline phosphatase or serum transaminase have been reported. Monitor liver function closely in patient who develop anorexia, weight loss, or pruritus, and in patients with pre-existing liver disease. Liver function tests are recommended at initiation of therapy.

Because allopurinol has been associated with drowsiness, patients should be cautious when engaging in activities where alertness is mandatory.

An increase in acute attacks of gout have been observed during the early stages of use of allopurinol, even when normal or subnormal serum uric acid levels have been reached. Accordingly, maintenance doses of colchicine generally should be given prophylactically when allopurinol therapy is started. The administration of colchicine or anti-inflammatory agents may be necessary to suppress gouty attacks in some instances. The gout attacks usually become shorter and less severe after several months of treatment. The mobilization of urates from tissue deposits which lead to fluctuations in the serum uric acid levels may be a possible explanation for these attacks. Even with adequate allopurinol treatment, it may require several months to deplete the uric acid pool adequately to achieve control of the acute attacks.

In the case of allopurinol injection, hydration to yield a daily urinary output of at least 2 L in adults and the maintenance of a slightly alkaline urine are recommended by the manufacturer to avoid the formation of xanthine calculi, and to prevent renal precipitation of urates in patients also receiving uricosuric drugs.

Some patients with preexisting renal disease or poor urate clearance have shown a rise in BUN during allopurinol therapy. Although the mechanism responsible for this has not been determined, patients with impaired renal function should be carefully monitored during the early stages of allopurinol use and the dosage decreased or the drug withdrawn if increased abnormalities in renal function appear and persist. Renal failure in association with allopurinol use has been reported among patients with hyperuricemia secondary to neoplastic diseases. Concurrent conditions such as multiple myeloma and congestive myocardial disease were present among those patients whose renal dysfunction increased after allopurinol therapy was started. Renal failure is frequently observed with the use of allopurinol therapy. Albuminemia has been observed in patients who developed clinical gout following chronic glomerulonephritis and chronic pyelonephritis. Patients with decreased renal function require lower doses of allopurinol therapy than those with normal renal function. Periodic monitoring of renal function is recommended during the course of therapy.

Bone marrow depression has been observed in patients receiving allopurinol therapy, most of whom received concomitant drugs with the potential for causing this adverse event. This has occurred as early as 6 weeks to as long as 6 years after the start of allopurinol. Rarely, a patient may develop varying degrees of bone marrow depression, affecting one or more cell lines, while receiving allopurinol therapy alone.

Prothrombin time should be reassessed periodically in patients receiving dicumarol and allopurinol.

Dialysis

Allopurinol is dialyzable. The dose may be given post hemodialysis or a 50% supplemental dose given.

Other Comments

The maximum recommended daily dose is 800 mg. Due to an initial increased risk of gouty attacks, prophylactic colchicine or an NSAID should be given concurrently for at least the first 6 months of allopurinol therapy.

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