Allopurinol - instructions for use, dose, side effects, contraindications

Competitive (allopurinol in low concentrations) and non-competitive (oxypurinol, allopurinol in high concentrations) inhibition of xanthine oxidase, preventing the transition of hypoxanthine to xanthine and the formation of uric acid from it. Increased use of xanthine and hypoxanthine for the synthesis of nucleotides and nucleic acids. Reduction of the concentration of uric acid and its salts in serum and urine.

Pharmacological effects

Antihyperuricemic. Antifedial. Urolithic (urates). Increase in the concentration of xanthine and hypoxanthin in blood and urine.

Pharmacokinetics:

F - 50-90%. VD - 0,87 ± 0,13 l / kg. Does not bind to plasma proteins. Biotransformation in the liver, active metabolite - oxypurinol. T1 / 2 allopurinol - 1-3 hours, T1 / 2 oxipurinol - 12-30 hours (an average of 15 hours), an increase in CRF. Cl 9.9 ± 2.4 mg / ml / min. Elimination of the kidneys 70-76% in the form of oxypurinol, 12% - unchanged allopurinol, with faeces - 20%. Removed during hemodialysis.

Indications:

- diseases accompanied by hyperuricemia (treatment and prevention)

- gout(primary and secondary)

- Renal stone disease (with the formation of urates)

- hyperuricemia (primary and secondary)

- diseases accompanied by increased decay of nucleoproteins and an increase in the content of uric acid in the blood, including various hemoblastoses (acute leukemia, chronic myelogenous leukemia, lymphosarcoma)

- cytostatic and radiation therapy of tumors (including children) (weak and unreliable evidence of efficacy in the treatment of mucositis of the oral cavity)

- psoriasis

- Extensive traumatic injuries

- enzymatic disorders (Lesch-Nichin syndrome)

- Violations of purine metabolism in children

- uric acid nephropathy with impaired renal function (renal failure)

- recurrent mixed oxalate-calcium kidney stones (in the presence of uricosuria)

ICD-10

XIII.M05-M14.M10 Gout

Contraindications:

Hypersensitivity, hepatic insufficiency, chronic renal failure (stage of azotemia), primary (idiopathic) hemochromatosis, asymptomatic hyperuricemia, acute attack of gout, pregnancy, breast-feeding.

Carefully:

Renal failure, CHF, diabetes, AH. Children's age (up to 14 years is prescribed only during cytostatic therapy of leukemia and other malignant diseases, as well as symptomatic treatment of enzyme disorders).

Pregnancy and lactation:

Pregnancy

Recommendations FDA category C. Adequate and well-controlled studies on humans have not been conducted. In small uncontrolled studies did not have a negative effect on the fetus. The animals had a teratogenic effect and increased the frequency of intrauterine death. Do not apply!

Lactation

Penetrates into breast milk. Violations are not registered. Do not apply!

Dosing and Administration:

Diseases accompanied by hyperuricemia (treatment and prevention). Podagra (primary and secondary). The low severity of gout symptoms is 200-300 mg / day, severe gout with tofusi is 400-600 mg / day, for a lesser risk of gout exacerbation - 100 mg / day with a weekly increase of 100 mg (until the uric acid content in the plasma decreases to 6 mg / dL). The onset of action after 2-3 days, the maximum effect develops after 1-3 weeks of constant admission, the duration of the action is 1-2 weeks after discontinuation of therapy. Renal stone disease (with the formation of urates).200-300 mg / day, with chronic renal failure, the dose is reduced: with CC 10-20 ml / min - 200 mg, 10 ml / min - 100 mg, <3 ml / min - 100 mg after 36-72 hours. Hyperuricemia (primary and secondary). In diseases accompanied by increased disintegration of nucleoproteins and increased levels of uric acid in the blood, including with various hemoblastoses (acute leukemia, chronic myelogenous leukemia, lymphosarcoma). With cytostatic and radiation therapy of tumors (including children) (weak and unreliable evidence of efficacy in the treatment of mucositis of the oral cavity). During the first 2-3 days 600-800 mg / day, abundant fluid intake. In case of psoriasis. In case of extensive traumatic injuries. Due to enzymatic disorders (Lesch-Nichena syndrome). Violations of purine metabolism in children. Myocardial nephropathy with impaired renal function (renal failure). Recurrent mixed oxalate-calcium kidney stones (in the presence of uricosuria). Inside after eating in 2 divided doses or once. Doses exceeding 300 mg, take a fraction. The minimum effective dose is 100-200 mg / day, the maximum is 800-900 mg / day.

When adding allopurinol to uricosuric drugs, its dose should be gradually increased, and the dose of uricosuric drugs should be reduced. Daily diuresis - at least 2 liters, the pH of the urine is neutral or slightly alkaline.

Use in children

Prevention of hyperuricemia associated with antitumor chemotherapy, prevention of urate nephropathy, Lesch-Nichena syndrome (enzyme-conditioned hyperuricemia). Inside. 1 month to 15 years: 10-20 mg / kg / day (maximum 400 mg) after meals. 15-18 years: from 100 mg / day after meals, the dose is selected depending on the concentration of uric acid in the blood / urine (maximum 900 mg), doses of more than 300 mg are taken in several doses.

Side effects:

Allergic dermatitis. Diarrhea, drowsiness, headache, indigestion, abdominal pain, alopecia, nausea, vomiting, fever, muscle pain. Agranulocytosis, aplastic anemia, thrombocytopenia, nasal bleeding, allergic vasculitis, exfoliative dermatitis, erythema multiforme, hepatotoxicity, allopurinol-induced allergy, weakness of nail plates, toxic epidermal necrolysis, peripheral neuritis, kidney stones (xanthine), acute renal failure, Stevens-Johnson syndrome.

Overdose:

Nausea, vomiting, diarrhea, dizziness, oliguria. Treatment is symptomatic, hemodialysis or peritoneal dialysis.

Interaction:

Alcohol, diazoxide, mecamylamine, pyrazinamide - an increase in the plasma concentration of uric acid, the need to adjust the dose of allopurinol.

Azathioprine, mercaptopurine - oppression of xanthine oxidase may result in increased therapeutic and toxic effects of these agents.

Anticoagulants, derivatives of coumarin and indanedione inhibit the metabolism of anticoagulants, enhance their effect.

Vidarabine - increased risk of neurotoxic effects and other side effects of virabina.

Dakarbazine, sulfinpyrazone - potentiation of inhibition of xanthine oxidase, an increase in the hypo-uricemic effect.

Xanthines: theophylline, aminophylline, oxypheline - increased plasma concentrations of xanthines, an increased risk of overdose.

Penicillins - increased risk of rash.

Probenecid, etebenecid - increased excretion of oxypurinol (the main active metabolite of allopurinol), however, combined use reduces the concentration of uric acid in the blood.

Antitumor agents - an increase in the plasma concentration of uric acid, the need to correct the dose of allopurinol. Increased risk of oppression of bone marrow hematopoiesis.

Remedies that acidify urine, such as ammonium chloride, ascorbic acid, potassium or sodium phosphate, - increased risk of formation of xanthine stones.

Thiazide diuretics - prescribe with caution, especially those with impaired renal function; risk of development of hypersensitivity reactions to allopurinol.

Chlorpropamide is a violation of the elimination of chlorpropamide by the kidneys, an increase in its plasma concentration.

Cyclosporine - a metabolic disorder of cyclosporine, a risk of toxic effects.

Special instructions:

Common to all agents for treating gout.

To prevent stone formation, it is advisable to consume abundant alkaline drink, to limit the intake of foods high in purines.

Monitoring the concentration of uric acid in the blood and urine, OAK, liver and kidney function, PV.

Distinctive characteristics.

Structural analogue of hypoxanthine. In patients suffering from hyperuricemia, when 100 mg of allopurinol is combined with 20 mg of benzbromarone, the serum uric acid level decreases more noticeably than when 300 mg of allopurinolB10 is administered.

Instructions

Allopurinol (Allopurinolum)