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|Allopurinol 300 mg|
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Pharmacological properties of the drug Allopurinol
Theagent, inhibiting xanthine oxidase, prevents the transition of hypoxanthine to xanthine and the formation of uric acid from it. Reduces the concentration of uric acid and its salts in body fluids, helps dissolve existing urate deposits, and prevents their formation in tissues and kidneys. By reducing the transformation of hypoxanthine and xanthine, it enhances their use for the synthesis of nucleotides and nucleic acids. The accumulation of xanthines in the plasma does not disrupt the normal exchange of nucleic acids, precipitation and precipitation of xanthines in the plasma does not occur (high solubility). The renal clearance of xanthines is 10 times higher than the clearance of uric acid, an increase in the excretion of xanthines in the urine is not accompanied by an increased risk of nephrourolithiasis.
Absorption after a single oral administration of 300 mg is 80-90%. Penetrates into breast milk. In the liver, about 70% of the dose is metabolized into the active metabolite - oxypurinol (alloxanthin). After a single dose of 300 mg - TCmax of allopurinol (2-3 μg / ml) -0.5-2 hours, oxypurinol (5-6 μg / ml) - 4.5-5 hours. T1 / 2 of allopurinol - 1-3 hours (rapid oxidation to oxypurinol and high glomerular filtration), T1 / 2 oxypurinol - 12-30 hours (average 15 hours). In the renal tubules, oxypurinol is largely reabsorbed (the mechanism of reabsorption is similar to that of uric acid). About 20% of the dose is excreted unchanged through the intestines; kidneys - 10% in the form of allopurinol and 70% in the form of oxypurinol. Hemodialysis is effective.
Diseases accompanied by hyperuricemia (treatment and prevention):
gout (primary and secondary),
kidney stones (with the formation of urates).
Hyperuricemia (primary and secondary), which occurs in diseases accompanied by increased disintegration of nucleoproteins and an increase in the content of uric acid in the blood, incl. with various hematoblastomas (acute leukemia, chronic myeloid leukemia, lymphosarcoma, etc.), with cytostatic and radiation therapy of tumors (including in children), psoriasis, extensive traumatic injuries due to enzyme disorders (Lesch-Nyhan syndrome), and with massive therapy of corticosteroids, when, due to the intensive disintegration of tissues, the amount of purines in the blood significantly increases. Purine metabolism disorders in children.
Uric acid nephropathy with impaired renal function (renal failure).
Recurrent mixed calcium oxalate kidney stones (if uricosuria is present).
Inside, after meals. Patients with low severity of symptoms of gout are prescribed orally 200-300 mg / day; for patients with severe gout with tophuses - 400-600 mg / day. The daily dose can be divided into 2 doses or taken at the same time; doses exceeding 300 mg are taken fractionally (with the appearance of side effects from the gastrointestinal tract). The minimum effective dose is 100-200 mg / day, the maximum is 800-900 mg / day. To reduce the risk of exacerbation of gout, treatment begins with low doses - 100 mg / day with a weekly increase of 100 mg (until the content of uric acid in plasma decreases to 6 mg / dL).
To prevent urate nephropathy during chemotherapy of malignant blood diseases, 600-800 mg / day is prescribed during the first 2-3 days and an abundant fluid intake is recommended. With recurrent oxalate kidney stones in patients with hyperuricosuria - 200-300 mg / day; with chronic renal failure, the dose is reduced: with CC 10-20 ml / min - the maximum dose is 200 mg, 10 ml / min - 100 mg, less than 3 ml / min - the interval between taking 100 mg is 36-72 hours.
Children under 6 years old - 5 mg / kg / day, from 6 to 10 years - 10 mg / kg / day, from 15 years old is prescribed at the rate of 10-20 mg / kg / day or 100-400 mg / day. Dose adequacy is assessed after 48 hours, frequency of administration is 3-4 times a day. With severe chronic renal failure - 100 mg / day or 100 mg with an interval of more than 1 day. The lowest dose is recommended for elderly patients. When allopurinol is added to uricosuric drugs, its dose is gradually increased, while uricosuric drugs are reduced. During treatment, it is necessary to provide a daily diuresis of at least 2 liters, to maintain the pH of urine at a neutral or slightly alkaline level.
Hypersensitivity, liver failure, chronic renal failure (azotemia stage), primary (idiopathic) hemochromatosis, asymptomatic hyperuricemia, acute gout attack, pregnancy, lactation period.
Carefully. Renal failure, CHF, diabetes mellitus, arterial hypertension. Children's age (up to 14 years old is prescribed only during cytostatic therapy of leukemias and other malignant diseases, as well as symptomatic treatment of enzyme disorders).
Category of action on the fetus.
Uricosuric drugs increase the renal clearance of the active metabolite of oxypurinol, thiazide diuretics slow down (increase toxicity).
Enhances the effect of oral hypoglycemic drugs. Increases blood concentration and toxicity (inhibits metabolism) of azathioprine, mercaptopurine, methotrexate, adenine arabinoside, xanthines (theophylline, aminophylline).
Colchicine, ASA increase the effectiveness (salicylates in large doses reduce the effectiveness).
It lengthens T1 / 2 of indirect coumarin anticoagulants, increases the hypoprothrombinemic effect.
Ampicillin, amoxicillin increase the incidence of skin rashes; cyclophosphamide, doxorubicin, bleomycin, procarbazine increase the risk of bone marrow aplasia.
When taken together with Fe-containing drugs, Fe accumulation in the liver tissues is possible.
The risk of toxicity increases when combined with ACE inhibitors, especially captopril; this is most clearly manifested in renal failure. Increases plasma concentrations of cyclosporine, which increases the risk of nephrotoxicity.
Thiazide diuretics, furosemide, ethacrynic acid and thiophosphamide, pyrazinamide, uricosuric drugs reduce the antihyperuricemic effect.
Asymptomatic uricosuria is not an indication for appointment.
With adequate therapy, it is possible to dissolve large urate stones in the renal pelvis and get them into the ureter (renal colic). Children are prescribed only for malignant neoplasms and congenital disorders of purine metabolism.
You should not start therapy until the acute attack of gout has completely stopped; during the first month of treatment, prophylactic NSAIDs or colchicine are recommended; in the case of an acute attack of gout during treatment, anti-inflammatory drugs are additionally prescribed.
In case of impaired renal and liver function (the risk of side effects increases), the dose is reduced. The use of azathioprine or 6-mercaptopurine against the background of allopurinol allows a decrease in their doses by 4 times. Combine with caution with vidarabine.
From the digestive system: dyspepsia, diarrhea, nausea, vomiting, abdominal pain, stomatitis, hyperbilirubinemia, cholestatic jaundice, increased activity of "hepatic" transaminases and alkaline phosphatase, rarely hepatonecrosis, hepatomegaly, granulomatous hepatitis. From the CVS: pericarditis, increased blood pressure, bradycardia, vasculitis. From the musculoskeletal system: myopathy, myalgia, arthralgia.
From the nervous system: headache, peripheral neuropathy, neuritis, paresthesia, paresis, depression, drowsiness.
From the senses: perversion of taste, loss of taste, visual impairment, cataract, conjunctivitis, amblyopia. From the genitourinary system: acute renal failure, interstitial nephritis, increased urea concentration (in patients with initially reduced renal function), peripheral edema, hematuria, proteinuria, decreased potency, infertility, gynecomastia. From the side of hematopoiesis: agranulocytosis, anemia, aplastic anemia, thrombocytopenia, eosinophilia, leukocytosis, leukopenia. Allergic reactions: skin rash, pruritus, urticaria, exudative erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), purpura, bullous dermatitis, eczematous dermatitis, exfoliative dermatitis, rarely bronchospasm.
Others: furunculosis, alopecia, diabetes mellitus, dehydration, nosebleeds, necrotizing tonsillitis, lymphadenopathy, hyperthermia, hyperlipidemia.
Overdose. Symptoms: nausea, vomiting, diarrhea, dizziness, oliguria.
Treatment: forced diuresis, hemo- and peritoneal dialysis.