Description
Allopurinol Pharmacodynamics
A remedy that interferes with the synthesis of uric acid. It is a structural analog of hypoxanthine. It inhibits xanthine oxidase enzyme, which is involved in conversion of hypoxanthine into xanthine and xanthine into uric acid. This is due to a decrease in the concentration of uric acid and its salts in the liquid media of the body and urine, which helps to dissolve existing urate deposits and prevents their formation in the tissues and kidneys. Allopurinol administration increases urinary excretion of hypoxanthine and xanthine.
Indications
Treatment and prevention of gout and hyperuricaemia of various genesis (including in combination with nephrolithiasis, renal failure, urate nephropathy). Recurrent mixed oxalate-calcium kidney stones in the presence of hyperuricosuria. Increased formation of urate due to enzyme disorders. Prevention of acute nephropathy in cytostatic and radiation therapy for tumors and leukemia, as well as complete therapeutic fasting.
Contraindications .
Severe liver and/or renal dysfunction, pregnancy, lactation, hypersensitivity to allopurinol.
Dosage and administration
- Inside, after a meal, with plenty of water. The daily urine volume should be more than 2 liters, and the urine reaction should be neutral or slightly alkaline. The daily dose of more than 300 mg should be divided into several doses.
- In adults, the drug is prescribed in a daily dose of 100-200 mg/day in mild disease, 300-600 mg/day in moderate disease, 700-900 mg/day in severe disease. The dose of the drug is adjusted individually, the effectiveness of therapy is monitored in the initial stages by repeated determination of uric acid levels in blood (desirable level <0.36 mmol/l). Decrease of uric acid level under the influence of the drug occurs in 24-48 hours.
To reduce the risk of gout exacerbation, treatment begins with a dose of 100-300 mg/day, with weekly, if necessary, increasing the dose by 100 mg/day. - For prevention of urate nephropathy in anti-tumor therapy, allopurinol is prescribed in a daily dose of 600-800 mg and the treatment is continued during 2-3 days.
In recurrent oxalate kidney stones in patients with hyperuricosemia, the drug dose is 200-300 mg/day. - Children from 10 to 15 years of age are prescribed 10-20 mg/kg/day or 100-400 mg/day; up to 10 years of age, 5-10 mg/kg/day.
- In patients with impaired renal excretory function, the daily dose of allopurinol should be reduced. During the first 6-8 weeks of treatment, regular liver function tests are necessary, in blood diseases regular laboratory monitoring is required.
- In chronic renal insufficiency, it is necessary to start with daily dose not more than 100 mg/day at intervals longer than 1 day, increasing it only at insufficient therapeutic effect. Allopurinol dose is gradually increased when added to uricosuric drugs, and uricosuric agents are decreased. During treatment, it is necessary to ensure daily diuresis of at least 2 liters, maintain urine pH at neutral or slightly alkaline level.
- At creatinine Cl >20 ml/min, the usual doses of allopurinol are prescribed; at creatinine Cl <10-20 ml/min, the daily dose should not exceed 200 mg.
