Allopyrinolum of Sandoz®

General characteristics. Structure:

Active ingredient: allopurinol.
1 tablet contains Allopyrinolum 100 mg or 300 mg;
excipients: cellulose powdery, povidone, macrogoal 4000, кросповидон, talc, magnesium stearate, cellulose microcrystallic.

Pharmacological properties:

Pharmacodynamics. Active ingredient of the drug Allopyrinolum Sandoz — Allopyrinolum — and its main metabolite — оксипуринол — break synthesis of uric acid, have urostatichesky property, based preferential on ability to suppress enzyme a xanthineoxidase, catalyzing oxidation of hypoxanthine to xanthine and xanthine to uric acid that leads to decrease in concentration of uric acid and promotes dissolution of urates.
Pharmacokinetics. Allopyrinolum is quickly soaked up in a digestive tract. After oral administration is defined in plasma in 30–60 min.
Cmax of Allopyrinolum and its metabolite — an oksipurinol — are reached in plasma respectively through 1,5 and in 3–5 h after reception. Gastric absorption is absent, more favorable conditions for absorption in duodenal and thin guts. At a usual therapeutic dose of 300 mg of Cmax of Allopyrinolum in plasma from 1 to 2,6 mkg/ml, on average — 1,8 mkg/ml fluctuate. For an oksipurinol the corresponding indicators make from 5 to 11 mkg/ml, on average — 8,4 mkg/ml.
In 24 h after oral administration of a single dose of 300 mg of Allopyrinolum average concentration of an oksipurinol in a blood plasma makes 3,78 mkg/ml.
Taking into account long T½ of an oksipurinol cumulation was noted at the beginning of therapy. The balance is reached approximately in a week. At patients with normal function of kidneys concentration in a blood plasma does not increase.
The volume of distribution of Allopyrinolum makes about 1,6 l/kg. Allopyrinolum quickly (T½ is about 2 h) is oxidized thanks to a xanthineoxidase and aldehyde oxidase to an oksipurinol which is also powerful inhibitor of a xanthineoxidase, however contacts enzyme more slowly.
Neither Allopyrinolum, nor its main metabolite have no the expressed affinity to proteins of plasma. Allopyrinolum is removed mainly by kidneys, and less than 10% are removed in not changed look. About 20% of the entered Allopyrinolum are removed with a stake in 48–72 h Oksipurinol is brought with urine in not changed look after a canalicular reabsorption.
Significant individual differences are characteristic of T½ of an oksipurinol. It makes 18–43 h at healthy volunteers, and in some cases (for example at a diet without purine) reaches 70 h. The renal failure leads to prolongation of T½ of an oksipurinol therefore at use of Allopyrinolum for patients with renal failures it is necessary to adhere to recommendations concerning a dosage.
Absolute bioavailability of 100 and 300 mg of Allopyrinolum makes respectively 67 and 90%.

Indications to use:

Adults
Treatment of a hyperuricemia (with the level of uric acid in blood serum within 500 µmol (8,5 mg / 100 ml) and above when the hyperuricemia is not controlled by a diet); the diseases caused by increase in level of uric acid in blood, especially at gout, an uratny nephropathy and an uratny urolithiasis; secondary hyperuricemia of various etiology; primary and secondary hyperuricemia at various hemoblastoses (an acute leukosis, a myelosis, a lymphosarcoma).
Allopyrinolum of 100 mg
Children
Treatment of the uratny nephropathy which resulted from treatment of leukemia; secondary hyperuricemia of various origin; inborn enzymatic insufficiency, in particular Lesh's syndrome — Niyena (partial or full deficit гипоксантин-гуанин-фосфорибозилтрансферазы) and inborn deficit adenine-fosforiboziltransferazy.

Route of administration and doses:

Pill is taken after food, without chewing, washing down with a large amount of liquid.
Adults
The daily dose is defined individually depending on the level of uric acid in blood serum and usually makes from 100 to 300 mg of Allopyrinolum of 1 times a day. For decrease in risk of side reactions treatment it is necessary to begin with reception 100 mg of Allopyrinolum of 1 times a day.
If necessary, if the level of uric acid in blood serum decreases insufficiently, the initial dose is gradually raised on 100 mg by each 1–3 weeks to obtaining the maximum effect. The maintenance dose usually makes 200–600 mg/days, however in some cases the dose can be raised to 600–800 mg/days.
If the daily dose of Allopyrinolum exceeds 300 mg, it is divided into 2–4 receptions. At increase in a dose control of level of an oksipurinol in blood serum which should not exceed 15 mkg/ml (100 µmol) is necessary.
Duration of treatment depends on a current of a basic disease.
The maximum daily dose — 800 mg.
Children
To children aged from 15 years Allopyrinolum appoint in a daily dose 10–20 mg to 1 kg of body weight. Frequency rate of reception — 3 times a day. The maximum daily dose — 400 mg.
Patients with a renal failure.
Treatment begin 100 mg which is raised only when efficiency of drug is insufficient with a daily dose. When determining a dose of drug are guided by an indicator of clearance of creatinine.

Clearance of creatinine                             Daily dose

    > 20                             ml/min. 100-300 mg of Allopyrinolum
 10–20                            ml/min. 100-200 mg of Allopyrinolum
     <10                 ml/min. 100 mg of Allopyrinolum or high doses through big
                                         intervals (for example in 1–2 days or more in dependence
                                         from a condition of the patient and functional capacity of kidneys)

Patients who are on a hemodialysis have to apply 300–400 mg of Allopyrinolum after each session (2–3 times a week).

Features of use:

Drug is not recommended to be used if the level of uric acid is lower than 506 µmol/l (there correspond 8,5 mg / 100 to ml), at observance of recommendations concerning a diet and lack of damage of kidneys. Not to use products with the high content of purine (for example an offal: kidneys, brain, liver, heart and language; meat gains and alcohol, especially beer).
At hypersensitivity reaction emergence (rash) use of Allopyrinolum should be stopped immediately.
At a renal failure and a liver or earlier established disturbances of a hemogenesis especially careful medical control is necessary. For patients with renal failures or a liver it is necessary to consider the corresponding recommendations concerning doses. At patients with AG or heart failure which accept APF inhibitors or diuretics it is necessary to apply Allopyrinolum with extra care.
At treatment of gout and an urolithiasis the volume of the emitted urine has to make not less than 2 l/days.
For prevention of increase in concentration of uric acid in serum or urine that can occur at radiotheraphy or chemotherapy of new growths, and also at Lesh's syndrome — Niyena, except Allopyrinolum it is necessary to use a large amount of liquid for maintenance of a sufficient diuresis. It is possible to make urine alkalization for improvement of removal of uric acid that leads to dissolution of urates / uric acid.
If the uratny nephropathy and other pathological changes already led to a renal failure, the dose should be otkorrigirovat according to indicators of function of kidneys.
In the presence of attacks of acute gout treatment by Allopyrinolum should not be begun before their total disappearance. In an initiation of treatment Allopyrinolum bad attacks of gout can amplify as a result of mobilization of a large amount of uric acid. Therefore during the first 4 weeks of treatment simultaneous use of analgetics or colchicine is necessary.
In the presence in a renal pelvis of large stones of uric acid it is impossible to exclude that at treatment by Allopyrinolum a part of stones can be dissolved and get into a bladder.
Use during pregnancy or feeding by a breast
There are no sufficient data concerning use of Allopyrinolum during pregnancy. As Allopyrinolum influences purine metabolism, and the potential risk for the person is unknown, Allopyrinolum is not recommended to apply during pregnancy. Allopyrinolum is allocated in breast milk therefore drug should not be accepted during feeding by a breast.
Children. Drug is not used at children aged up to 15 years.
Ability to influence speed of response at control of vehicles or work with other mechanisms
Before clarification of individual reaction to Allopyrinolum it is necessary to be careful at control of vehicles or work with other mechanisms because of possibility of dizziness or drowsiness.

Side effects:

Assessment of side effects is based on information on their frequency: very often (≥1/10), it is frequent (≥1/100, <1/10), infrequently (≥1/1000, <1/100), is rare (≥1/10 000, <1/1000), is very rare (<1/10 000), frequency is unknown (it is impossible to estimate by means of available data).
In an initiation of treatment reactive attacks of gout can arise Allopyrinolum.
Manifestations of side reactions are most frequent at a renal and/or liver failure or at simultaneous use with ampicillin or amoxicillin.
From system of blood: seldom — heavy injury of marrow (thrombocytopenia, an agranulocytosis, aplastic anemia) especially at patients with a renal failure; very seldom — an angioimmunoblastny lymphadenopathy (reversible after cancellation of Allopyrinolum), changes of indicators of blood (a leukopenia, a leukocytosis, an eosinophilia).
From immune system: seldom — exfoliation, a lymphadenopathy, an arthralgia, Stephens's syndrome — Johnson, a Lyell's disease, an epidermal necrolysis, a vasculitis, hypersensitivity reactions (fever, rash, a fever, a joint pain), an abnormal liver function (reversible increase in transaminases and ShchF), an acute cholangitis and ksantinovy stones; very seldom — an acute anaphylaxis.
Metabolic disturbances: very seldom — a diabetes mellitus, a lipidemia.
Mental disturbances: very seldom — a depression.
From a nervous system: very seldom — an ataxy, peripheral neuritis, disturbance of flavoring feelings, a lump, a headache, neuropathy, paralysis, dizziness, drowsiness, paresthesias.
From an organ of sight: very seldom — a cataract, a degeneration of a retina, a vision disorder.
From cardiovascular system: very seldom — arterial hypotension; frequency is unknown — bradycardia.
From respiratory system: very seldom — quinsy.
From a GIT: very seldom — a hematemesis, a steatorrhea, stomatitis, nausea, vomiting, diarrhea.
From a liver: seldom — an abnormal liver function from symptomless increase in indicators of function of a liver to hepatitis (including a necrosis of a liver and granulematozny hepatitis).
From skin: very seldom — an alopecia, a furunculosis, a Quincke's edema, decolouration of hair.
The most widespread skin reactions (about 4%) arise during any period of treatment and can be shown in the form of a purpura, makulopapulezny, squamous or exfoliative rash.
At emergence of these reactions reception of Allopyrinolum should be stopped immediately. After reduction of expressiveness of symptoms it is possible to appoint drug in low doses (for example 50 mg/days). If necessary the dose can be raised gradually. At repeated display of skin rash administration of drug needs to be stopped as heavy generalized reactions of hypersensitivity can appear.
From a musculoskeletal system: very seldom — muscular pain.
From an urinary system: very seldom — a hamaturia, uraemia.
From reproductive system: very seldom — a gynecomastia, impotence, infertility.
General disturbances: very seldom — a febricula, an adynamy, hypostases.

Interaction with other medicines:

Allopyrinolum slows down removal of a probenetsid.
Efficiency of Allopyrinolum decreases at use of the drugs capable to remove uric acid — Sulfinpyrazonum, a probenitsid and a benzbromaron or salicylates.
If Allopyrinolum is accepted along with 6 Mercaptopurinum or Azathioprinum, usual doses of the last should be reduced to 25% as metabolism of these drugs is slowed down in connection with xanthineoxidase inhibition, and their effect is prolonged.
At simultaneous use of Allopyrinolum with ampicillin or amoxicillin there is a probability of emergence of allergic reactions (dieback) therefore the patients accepting Allopyrinolum have to apply other antibiotics.
Simultaneous use of Allopyrinolum and captopril can increase risk of skin reactions, especially at chronic diseases of kidneys.
The effect of anticoagulants (coumarin) therefore more frequent control of coagulability of blood, and also a dose decline of derivatives of coumarin is required can amplify.
At a renal failure, especially at simultaneous use of Allopyrinolum, the hypoglycemic effect of Chlorproramidum can be prolonged that demands a dose decline.
In high doses Allopyrinolum inhibits theophylline metabolism therefore in an initiation of treatment Allopyrinolum or at increase in its dose it is necessary to control theophylline level in plasma.
At use of Allopyrinolum to cytostatics (for example change of composition of blood, than at separate administration of active agents therefore indicators of blood should be controlled through short intervals of time happens cyclophosphamide, doxorubicine, bleomycin, Procarbazinum, alkyl halides) more often.
At simultaneous use of Allopyrinolum with vidarabiny T½ of the last of plasma therefore this combination should be applied with care in order to avoid increase in expressiveness of side reactions is prolonged.
At use of Allopyrinolum concentration of cyclosporine in plasma — possibly increase in expressiveness of side reactions at cyclosporine can increase.
Allopyrinolum can break metabolism of Phenytoinum in a liver; it is unknown whether have these data clinical value.
Allopyrinolum can lead to increase in expressiveness of side reactions of separate medicines, in particular: at simultaneous use with captopril the risk of emergence of skin reactions can increase, especially in case of a chronic renal failure; use of Allopyrinolum with cytostatics leads to more frequent changes of indicators of blood, than in case of separate use of these medicines therefore blood test should be done through short intervals of time; at use of Allopyrinolum together with ampicillin and amoxicillin of emergence of allergic reactions it is possible to expect more often.

Contraindications:

Hypersensitivity to Allopyrinolum or any of drug components. Heavy renal failures (clearance of creatinine <2 ml/min.) and liver. Period of pregnancy and feeding by a breast.

Overdose:

Symptoms. After a single dose of 20 g one patient had such symptoms as nausea, vomiting, diarrhea and dizziness. The dose of 22,5 g of Allopyrinolum did not cause undesirable effects in other patient. After long reception of 200-400 mg of Allopyrinolum a day at patients with renal failures heavy symptoms of intoxication (skin reactions, fever, hepatitis, an eosinophilia and an exacerbation of a renal failure) are described.
Treatment. Therapy is symptomatic. If necessary — a hemodialysis. There is no specific antidote.

Storage conditions:

Period of validity of 5 years. To store at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 100 mg, No. 50

Tablets of 300 mg, No. 50