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

100 mg tablets: lactose monohydrate 50 mg, potato starch 32 mg, povidone K-25 6.5 mg, talc 6 mg, magnesium stearate 3 mg, sodium carboxymethyl starch (type A) 2.5 mg;

300 mg tablets: magnesium stearate 3 mg, silicon dioxide colloidal anhydrous 3 mg, gelatin 12 mg, sodium carboxymethyl starch (type A) 20 mg, microcrystalline cellulose 52 mg.

Description:

Tablets 100 mg: Round flat tablets of white or grayish-white color, with a facet, with a risk on one and with engraving E 351 on the other side, without or almost no smell.

Tablets 300 mg: Round flat tablets of white or grayish-white color, with a facet, with a risk on one and with engraving E 352 on the other side, without or almost no smell.

With the help of the risks, tablets can be divided into two identical doses.

Pharmacotherapeutic group:Antifungal agent - xanthine oxidase inhibitor

ATX: & nbsp

M.04.A.A Inhibitors of uric acid synthesis

Pharmacodynamics:

Allopurinol is a structural analogue of hypoxanthine. Allopurinol, as well as its main active metabolite, oxypurinol, inhibit xanthine oxidase, an enzyme that converts hypoxanthine to xanthine, and xanthine to uric acid. Allopurinol reduces the concentration of uric acid in both serum and urine. Thus, it prevents the deposition of uric acid crystals in the tissues and (or) facilitates their dissolution. In addition to suppressing catabolism of purines in some (but not all) patients with hyperuricemia, a large amount of xanthine and hypoxanthine becomes available for the re-formation of purine bases, which leads to suppression of purine biosynthesis de novo by the feedback mechanism, which is mediated by inhibition of the hypoxanthine-guanine phosphoribosyl transferase enzyme. Other metabolites of allopurinol are allopurinol-riboside and oxypurinol-7 riboside.

Pharmacokinetics:

Suction

Allopurinol is active when given orally. It is quickly absorbed from the upper parts of the gastrointestinal tract.According to pharmacokinetic studies, allopurinol is determined in the blood after 30-60 minutes after administration. The bioavailability of allopurinol varies from 67% to 90%. The maximum concentration of the drug in the blood plasma is usually recorded approximately 1.5 hours after oral administration. The concentration of allopurinol is then rapidly reduced. After 6 hours after administration, only the trace concentration of the drug is determined in the blood plasma. The maximum concentration of the active metabolite - oxypurinol is usually recorded 3-5 hours after oral administration of allopurinol. The level of oxypurinol in the blood plasma decreases significantly more slowly.

Distribution

Allopurinol almost does not bind to blood plasma proteins, therefore changes in the level of binding to proteins should not have a significant effect on the clearance of the drug. The apparent volume of distribution of allopurinol is approximately 1.6 liters / kg, indicating a fairly pronounced absorption of the drug by the tissues. The content of allopurinol in various human tissues has not been studied, but it is very likely that allopurinol and oxypurinol in the maximum concentration accumulate in the liver and intestinal mucosa, where high activity of xanthine oxidase is recorded.

Biotransformation

Under the action of xanthine oxidase and aldehyde oxidase allopurinol is metabolized with the formation of oxypurinol. Oxipurinol inhibits the activity of xanthine oxidase. However, oxypurinol is not a potent inhibitor of xanthine oxidase, compared to allopurinol, but its half-life is much longer. Due to these properties, after taking a single daily dose of allopurinol, effective inhibition of xanthine oxidase activity is maintained for 24 hours. In patients with normal renal function, the content of oxypurinol in the blood plasma slowly increases until equilibrium concentration is reached. After receiving allopurinol at a dose of 300 mg per day, the concentration of allopurinol in the blood plasma, as a rule, is 5-10 mg / l. Other metabolites of allopurinol include allopurinol-ribozide and oxypurinol-7-riboside.

Excretion

Approximately 20% of the per os Allopurinol is excreted with feces unchanged.About 10% of the daily dose is excreted by the glomerular apparatus of the kidney in the form of unchanged allopurinol. Another 70% of the daily dose of allopurinol is excreted in the urine in the form of oxypurinol. Oxipurinol is excreted by the kidneys unchanged, but in connection with tubular reabsorption it has a long half-life. The half-life of allopurinol is 1-2 hours, while the half-life of oxypurinol varies from 13 to 30 hours. Such significant differences are probably due to differences in the structure of studies and / or creatinine clearance in patients.

Patients with impaired renal function

In patients with impaired renal function, excretion of allopurinol and oxypurinol can be significantly slowed down, which, with prolonged therapy, leads to an increase in the concentration of these compounds in the blood plasma. In patients with impaired renal function and creatinine clearance of 10-20 ml / min after long-term therapy with allopurinol at a dose of 300 mg per day, the concentration of oxypurinol in the blood plasma reached approximately 30 mg / l. This concentration of oxypurinol can be determined in patients with normal renal function against the background of therapy with allopurinol at a dose of 600 mg per day.Therefore, in the treatment of patients with impaired renal function, the dose of allopurinol should be reduced.

Elderly patients

In elderly patients, significant changes in the pharmacokinetic properties of allopurinol are unlikely. Exceptions are patients with concomitant renal pathology (see section Pharmacokinetics in patients with impaired renal function).

Indications:

Suppression of the formation of uric acid and its salts with the confirmed accumulation of these compounds (eg, gout, cutaneous tofusi, nephrolithiasis) or the estimated clinical risk of their accumulation (for example, treatment of malignant tumors can be complicated by the development of acute urinary nephropathy).

The main clinical conditions that can be accompanied by the accumulation of uric acid and its salts include:

- idiopathic gout;

- urolithiasis (formation of concrements from uric acid);

- acute urinary nephropathy;

- tumor diseases and myeloproliferative syndrome with a high rate of renewal of the cell population, when hyperuricemia occurs spontaneously or after cytotoxic therapy;

- certain enzymatic disorders accompanied by hyperproduction of uric acid salts, for example, reduced hypoxanthine guanine phosphoribosyltransferase activity (including Lesch-Nayhan syndrome), reduced activity of glucose-6-phosphatase (including glycogenoses), increased phosphoribosyl pyrophosphate synthetase activity, increased phosphoribosyl pyrophosphate activity -amido-transferase, decreased activity of adenine-phosphoribosyltransferase.

Treatment of urolithiasis accompanied by the formation of 2,8-dihydroxyadenine (2,8-DHA) stones in connection with a decreased activity of adenine phosphoribosyltransferase.

Prevention and treatment of urolithiasis, accompanied by the formation of mixed calcium-oxalate stones in the background of hyperuricosuria, when diet and increased fluid intake were unsuccessful.

Contraindications:

Hypersensitivity to allopurinol or any of the excipients that make up the drug.

Hepatic insufficiency, chronic renal failure (stage of azotemia), primary hemochromatosis, asymptomatic hyperuricemia, acute attack of gout, childhood up to 3 years (taking into account the solid dosage form)

Pregnancy, the period of breastfeeding (see.section "Application during pregnancy and breastfeeding").

Patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take the drug (lactose monohydrate is included in the formulation).

Carefully:Dysfunctions of the liver, hypothyroidism, diabetes mellitus, arterial hypertension, simultaneous administration of angiotensin converting enzyme (ACE) inhibitors or diuretics, children's age (up to 15 years are prescribed only during cytostatic therapy of leukemias and other malignant diseases, as well as symptomatic treatment of enzyme disorders); elderly age.

Pregnancy and lactation:

Pregnancy

Currently, data on the safety of allopurinol therapy during pregnancy is not enough, although this drug has been widely used for a long time without obvious adverse effects. Pregnant women should not take Allopurinol-EGIS tablets, unless there is no less dangerous alternative treatment and the disease is more risky for the mother and fetus than taking the drug.

Breastfeeding period

According to existing reports, allopurinol and oxypurinol are excreted in breast milk. In women receiving allopurinol in a dose of 300 mg / day, the concentration of allopurinol and oxypurinol in breast milk reached, respectively, 1.4 mg / L and 53.7 mg / L. Nevertheless, there is no information on the effect of allopurinol and its metabolites on infants who are breastfeeding. Thus, the drug Allopurinol-EGIS tablets is not recommended during breastfeeding.

Dosing and Administration:

Inside. The drug should be taken once a day after meals, washed down with plenty of water. If the daily dose exceeds 300 mg or symptoms are observed intolerance from the gastrointestinal tract, then the dose should be divided into several receptions.

Adult patients

In order to reduce the risk of side effects, it is recommended to use allopurinol in an initial dose of 100 mg once a day. If this dose is not enough to properly reduce the concentration of uric acid in the blood serum, then the daily dose of the drug can be gradually increased to achieve the desired effect. Care should be taken if the renal function is impaired.With an increase in the dose of allopurinol every 1-3 weeks, it is necessary to determine the concentration of uric acid in the serum.

When choosing a dose of the drug, the following dosing regimens are recommended (depending on the chosen dosing regimen, tablets of 100 mg or 300 mg are recommended).

The recommended dose of the drug is: 100-200 mg per day for mild disease; 300-600 mg per day for moderate to moderate flow; 700-900 mg per day in severe conditions.

If the dose is calculated from the patient's body weight, the dose of allopurinol should be 2 to 10 mg / kg / day.

Children and adolescents under the age of 15

Recommended dose for children from 3 to 10 years: 5-10 mg / kg / day. For low doses, 100 mg tablets are used, which, with the help of risks, can be divided into two identical doses of 50 mg each. The recommended dose for children from 10 to 15 years is 10-20 mg / kg / day. The daily dose of the drug should not exceed 400 mg.

Allopurinol is rarely used for pediatric therapy. The exception is malignant oncological diseases (especially leukemia) and some enzymatic disorders (for example, Lesha-Naikhan syndrome).

Elderly patients

Since there is no specific data on the use of allopurinol in the population of elderly people, a minimal dose should be used to treat such patients, providing a sufficient reduction in serum uric acid concentration. Particular attention should be given to recommendations for the selection of a dose of the drug for patients with impaired renal function (see section Special instructions).

Renal impairment

Because the allopurinol and its metabolites are excreted from the body by the kidneys, impaired renal function can lead to a delay in the drug and its metabolites in the body, followed by an elongation of the half-life of these compounds from the blood plasma. In severe renal failure, it is recommended that allopurinol in a dose below 100 mg per day, or use single doses of 100 mg with an interval of more than one day.

If the conditions allow controlling the concentration of oxypurinol in the blood plasma, the dose of allopurinol should be selected so that the level of oxypurinol in the blood plasma is below 100 μmol / l (15.2 mg / l).

Allopurinol and its derivatives are removed from the body by hemodialysis.If hemodialysis sessions are held 2-3 times a week, it is advisable to determine the need for switching to an alternative treatment regimen - receiving 300-400 mg allopurinol immediately after hemodialysis (between hemodialysis drug is not accepted).

In patients with impaired renal function, the combination of allopurinol with thiazide diuretics should be performed with extreme caution. Allopurinol should be given at the lowest effective doses with careful monitoring of kidney function (see section Interaction with other drugs)

Dysfunction of the liver

If the liver function is impaired, the dose of the drug should be reduced. At an early stage of therapy, it is recommended to monitor laboratory parameters of liver function.

Conditions accompanied by increased exchange of uric acid salts (eg, tumor diseases, Lesha-Naikhan syndrome)

Before starting therapy with cytotoxic drugs, it is recommended to correct existing hyperuricemia and / or hyperuricosuria with allopurinol. Adequate hydration is very important,which helps maintain optimal diuresis, as well as alkalinization of urine, due to which the solubility of uric acid and its salts increases. The dose of allopurinol should be close to the lower limit of the recommended dose range.

If renal dysfunction is caused by the development of acute urinary nephropathy or other renal pathology, the treatment should continue in accordance with the recommendations presented in the section "Impairment of kidney function."

The measures described can reduce the risk of xanthine and uric acid accumulation complicating the course of the disease.

Monitoring Recommendations

To correct the dose of the drug, it is necessary to estimate the concentration of uric acid salts in blood serum, as well as uric acid and urate urate levels at optimal intervals.

Side effects:

There are no modern clinical data for determining the incidence of side effects. Their frequency may vary depending on the dose and on whether the drug was administered as monotherapy or in combination with other drugs.

Classification of frequency of side effects is based on a rough estimate, for the majority of side effects no data to determine the frequency of their development.

Classification of undesirable reactions depending on frequency of occurrence looks like in the following way:

very frequent (≥1/10),

frequent (from ≥1/100 to <1/10),

infrequent ≥1/1000 to <1/100),

rare (from ≥1/10000 to <1/1000),

very rare (<1/10000),

frequency is unknown (can not be determined from available data).

The undesirable reactions associated with allopurinol therapy observed in the postgrade period are rare or very rare. In the general population of patients in most cases are of an easy nature. The incidence of adverse events increases with impaired renal and / or liver function.

Infections and parasitic diseases: very rare: furunculosis.

Disorders from the blood and lymphatic system:

very rare: agranulocytosis, aplastic anemia, thrombocytopenia, granulocytosis, leukopenia, leukocytosis, eosinophilia and aplasia, relating only to erythrocytes.

There have been very few reports of thrombocytopenia, agranulocytosis, and aplastic anemia, especially in individuals with impaired renal and / or liver function, which underscores the need for extreme caution in these patient groups.

Immune system disorders:

infrequent: hypersensitivity reactions; rare: severe hypersensitivity reactions, including skin reactions with epidermal detachment, fever, lymphadenopathy, arthralgia, and / or eosinophilia (including Stevens-Johnson syndrome and toxic epidermal necrolysis) (see "Skin and subcutaneous tissue disorders" section). Concomitant vasculitis or reactions from the tissue may have various manifestations, including hepatitis, kidney damage, acute cholangitis, xanthine stones and, in very rare cases, convulsions. In addition, the development of anaphylactic shock was very rare. With the development of severe adverse reactions, allopurinol therapy immediately stop and do not resume. With delayed multi-organ hypersensitivity (known as drug hypersensitivity syndrome /DRESS/) the following symptoms can develop in different combinations: fever, skin rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, changes in liver function tests, disappearing bile duct syndrome (destruction or disappearance of intrahepatic bile ducts).If such reactions develop in any treatment period, Allopurinol-EGIS should be immediately discontinued and never restarted. Generalized hypersensitivity reactions developed in patients with impaired renal and / or liver function. Such cases were sometimes fatal; very rare: angioimmunoblastic lymphadenopathy. Angioimmunoblast Lymphadenopathy was very rarely diagnosed after lymph node biopsy for generalized lymphadenopathy. Angioimmunoblastic lymphadenopathy is reversible and regresses after cessation of therapy with allopurinol.

Disorders from the metabolism and nutrition:

very rare: diabetes mellitus, hyperlipidemia

Disorders of the psyche:

very rare: depression

Disturbances from the nervous system:

very rare: coma, paralysis, ataxia, neuropathy, paresthesia, drowsiness, headache, perversion of taste sensations

Disturbances on the part of the organ of sight:

very rare: cataract, visual impairment, macular changes

Hearing disorders and labyrinthine disorders:

very rare: dizziness (vertigo)

Heart Disease:

very rare: angina, bradycardia.

Vascular disorders:

very rare: increase in blood pressure

Disorders from the gastrointestinal tract: infrequent: vomiting, nausea, diarrhea;

In previous clinical studies, nausea and vomiting have been observed, but later observations confirmed that these reactions are not a clinically significant problem and can be avoided by prescribing allopurinol after meal.

very rare: recurrent bloody vomiting, steatorrhea, stomatitis, changes in the frequency of defecation

Frequency unknown: abdominal pain

Disturbances from the liver and bile ducts:

infrequent: asymptomatic increase in the concentration of hepatic enzymes (elevated levels of alkaline phosphatase and transaminase in the blood serum) rare: Hepatitis (including necrotic and granulomatous forms).

Dysfunction of the liver can develop without obvious signs of generalized hypersensitivity

Disturbances from the skin and subcutaneous tissues:

Frequent: rash; rare: severe skin reactions: Stevens-Johnson syndrome (SDS) and toxic epidermal necrolysis (TEN), very rare: angioedema, local medical ailment, alopecia, hair discoloration.

In patients receiving allopurinol, the most common adverse reactions from the skin. Against the background of drug therapy, these reactions can develop at any time. Skin reactions can be manifested by itching, maculopapular and scaly rashes. In other cases purple may develop. In rare cases, exfoliative skin lesions are observed (SSD / TEN). With the development of such reactions, therapy with allopurinol should be stopped immediately. If the reaction from the skin is light, then after the disappearance of these changes, you can resume taking allopurinol in a smaller dose (for example, 50 mg per day). Subsequently, the dose can be gradually increased. In case of recurrence of skin reactions, allopurinol therapy should be stopped and no longer restarted, as further administration of the drug may lead to the development of more severe hypersensitivity reactions (see "Immune system disorders").

According to existing information, against the background of therapy with allopurinol, angioedema has developed in isolation, as well as in combination with the symptoms of a generalized hypersensitivity reaction.

Disturbances from musculoskeletal and connective tissue:

very rare: myalgia.

Disorders from the nochek and urinary tract:

very rare: hematuria, renal insufficiency, uremia, frequency is unknown: urolithiasis disease.

Disorders from the reproductive system and breast:

very rare: male infertility, erectile dysfunction, gynecomastia.

General disorders and disorders at the injection site:

very rare: edema, general malaise, general weakness, fever.

According to existing information, against the background of therapy with allopurinol, fever developed both in isolation and in combination with the symptoms of a generalized hypersensitivity reaction (see "Immune system disorders")

Reports of possible adverse reactions

In case of adverse reactions, including those not indicated in this manual, the use of the drug should be discontinued.

In the post-marketing period, any information on possible adverse reactions is important, since these reports help to constantly monitor the drug's safety.Health care professionals are required to report any suspicions of adverse reactions to local pharmacovigilance authorities.

Overdose:

Symptoms: nausea, vomiting, diarrhea and dizziness. Severe overdose allopurinol can lead to a significant inhibition of xanthine oxidase activity. By itself, this effect should not be accompanied by undesirable reactions. An exception is the effect on concomitant therapy, in particular on the treatment with 6-mercaptopurine and (or) azathioprine.

Treatment:

The specific antidote of allopurinol is unknown. Adequate hydration, supporting the optimal diuresis, promotes the excretion of allopurinol and its derivatives in the urine. If there are clinical indications, hemodialysis is performed.

Interaction:

6-mercaptopurine and azathioprine

Azathioprine is metabolized to form 6-mercaptopurine, which is inactivated by the enzyme xanthine oxidase. In cases where therapy with 6-mercaptopurine or azathioprine is combined with allopurinol, patients should be assigned only one a quarter of the usual dose of 6-mercaptopurine or azathioprine, since inhibition of xanthine oxidase activity increases the duration of action of these compounds.

Vidarabine (adenine arabinoside)

In the presence of allopurinol, the half-life of vidarabine increases. With the simultaneous application of these drugs must be respected alertness to the increased toxic effects of therapy.

Salicylates and uricosuric agents

The main active metabolite of allopurinol is oxypurinol, which is excreted by the kidneys similarly to salts of uric acid. Therefore, drugs with uricosuric activity, such as probenecid or high doses of salicylates, can enhance the excretion of oxypurinol. In turn, increased excretion of oxypurinol is accompanied by a decrease in the therapeutic activity of allopurinol, but the significance of this type of interaction must be assessed individually in each case.

Chloropropamide

With the simultaneous use of allopurinol and chlorpropamide, patients with impaired renal function increase the risk of developing prolonged hypoglycemia, since the tubular excretion allopurinol and chlorpropamide compete with each other.

Anticoagulant coumarin derivatives

With simultaneous use with allopurinol, there was an increase in the effects of warfarin and other anticoagulants of coumarin derivatives. In this regard, it is necessary to carefully monitor the condition of patients receiving concomitant therapy with these drugs.

Phenytoin

Allopurinol is able to suppress the oxidation of phenytoin in the liver, but the clinical significance of this interaction is not established.

Theophylline

It is known that allopurinol depresses the metabolism of theophylline. Such an interaction can be explained by the involvement of xanthine oxidase in the process of biotransformation of theophylline in the human body. The concentration of theophylline in serum should be monitored at the beginning of concomitant therapy with allopurinol, and also with an increase in the dose of the latter.

Ampicillin and amoxicillin

In patients who simultaneously received ampicillin or amoxicillin and allopurinol, an increased incidence of skin reactions was recorded, compared with patients who did not receive similar concomitant therapy. The cause of this type of drug interaction is not established. However, patients receiving allopurinol, instead of ampicillin and amoxicillin it is recommended to prescribe other antibacterial drugs.

Cytotoxic drugs (cyclophosphamide, doxorubicin, bleomycin, procarbazine, mechlorethamine)

In patients suffering from tumor diseases (except leukemia) and receiving allopurinol, enhanced suppression of bone marrow activity by cyclophosphamide and other cytotoxic drugs was observed. Nevertheless, according to the results of controlled trials, in which patients who received cyclophosphamide, doxorubicin, bleomycin, procarbazine and (or) mechlorethamine (chloromethine hydrochloride), concomitant allopurinol therapy did not enhance the toxic effect of these cytotoxic drugs.

Cyclosporin

According to some reports, the concentration of cyclosporine in the blood plasma may increase against the background of concomitant therapy with allopurinol. With the simultaneous use of these drugs must take into account the possibility of increasing the toxicity of cyclosporine.

Didanosine

In healthy volunteers and HIV-infected patients receiving didanosine, against the background of concomitant therapy with allopurinol (300 mg per day) there was an increase in C_m_Oh(the maximum concentration of the drug in the blood plasma) and AUC (the area under the concentration-time curve) didanosine is approximately twice. The half-life of Didanosine did not change. As a rule, the simultaneous use of these drugs is not recommended. If concomitant therapy is unavoidable, a reduction in didanosine dose and careful monitoring of the patient's condition may be required.

ACE Inhibitors

Simultaneous use of ACE inhibitors with allopurinol is accompanied by an increased risk of developing leukopenia, so these drugs should be combined with caution.

Thiazide diuretics

The simultaneous use of thiazide diuretics, including hydrochlorothiazide, may increase the risk of side effects of hypersensitivity associated with allopurinol, especially in patients with impaired renal function.

Special instructions:

Syndrome of drug hypersensitivity, SSD and TEN

Against the background of the use of allopurinol, there have been reports of life-threatening reactions from the skin, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SSD / TEN).Patients should be informed of the symptoms of these reactions (progressive skin rash, often with vesicles and mucosal lesions) and carefully monitor their development. Most often, SSD / TEN develop during the first weeks of taking the drug. In the presence of signs and symptoms of SSD / TEN, the drug Allopurinol-EGIS should be immediately canceled and no longer prescribed!

The manifestation of hypersensitivity reactions to allopurinol can be very different, including maculopapular exanthema, drug hypersensitivity syndrome (DRESS) and SSD / TEN. These reactions are a clinical diagnosis and their clinical manifestations are the basis for making appropriate decisions. Therapy with Allopurinol-EGIS should be stopped immediately if skin rashes or other manifestations of hypersensitivity reaction appear. It is impossible to resume therapy in patients with hypersensitivity syndrome and SSD / TEN. Corticosteroids can be used to treat skin reactions with hypersensitivity.

Chronic renal dysfunction

Patients with chronic renal dysfunction have a greater risk of developing hypersensitivity reactions associated with allopurinol, including SSD / TEN.

Allele HLA-B*5801

It was found that the presence of an allele HLA-B*5801 is associated with the development of a hypersensitivity syndrome to allopurinol and SSD / TET. Allele frequency HLA- В * 5801 is different in different ethnic groups and can reach 20% in the Han population, about 12% in Koreans and 1-2% in Japanese and Europeans. The use of genotyping to make decisions about the therapy with allopurinol has not been investigated. If it is known that the patient is the carrier of the allele HLA-B*5801, then allopurinol It should be prescribed only if the benefit of the treatment exceeds the risk. It should be very closely monitor the development of the hypersensitivity syndrome and SSD / TEN. The patient should be informed of the need for immediate withdrawal of treatment at the first occurrence of such symptoms.

Impaired liver and kidney function

In the treatment of patients with impaired renal or hepatic function, the dose of allopurinol should be reduced. Patients receiving treatment for hypertension or heart failure (eg, patients taking diuretics or ACE inhibitors) may experience concomitant renal impairment, so allopurinol in this group of patients should be used with caution.

Asymptomatic hyperuricemia in itself is not an indication for the use of allopurinol. In such cases, the improvement of the patient's condition can be achieved through changes in diet and fluid intake along with the elimination of the underlying cause of hyperuricemia.

Acute attack of gout.

Allopurinol should not be used until the acute acute attack of gout is completely stopped, as this can provoke an additional exacerbation of the disease.

Similarly to uricosuric therapy, the onset of allopurinol treatment can trigger an acute attack of gout. In order to avoid this complication, it is recommended that preventive therapy with non-steroidal anti-inflammatory drugs or colchicine is carried out for at least one month prior to the appointment of allopurinol. Details on recommended doses, warnings and precautions can be found in the relevant literature.

If an acute attack of gout develops with allopurinol therapy, then the drug should be continued at the same dose, and an appropriate non-steroidal anti-inflammatory agent should be prescribed to treat the attack.

Xanthine deposits

In cases where the formation of uric acid is significantly increased (for example, malignant tumor pathology and corresponding antitumor therapy, Lesch-Nayhan syndrome), the absolute concentration of xanthine in urine in rare cases can increase significantly, which contributes to the deposition of xanthine in the tissues of the urinary tract. The likelihood of xanthine deposition in tissues can be minimized by adequate hydration, which ensures optimal urine dilution.

Injection of stones from uric acid

Adequate therapy with allopurinol may lead to the dissolution of large concrements from uric acid in the renal pelvis, however, the probability of wedging these concrements into the ureters is low.

Hemochromatosis

The main effect of allopurinol in the treatment of gout is to suppress the activity of the enzyme xanthine oxidase. Xanthine oxidase may be involved in reducing the content and excretion of iron deposited in the liver. Studies demonstrating the safety of allopurinol therapy in the population of patients with hemochromatosis are lacking.Patients with hemochromatosis, as well as their blood relatives allopurinol should be administered with caution.

Lactose

Each 100 mg tablet of the drug Allopurinol-EGIS contains 50 mg of lactose. Therefore, this drug should not be taken by patients with a rare hereditary intolerance to galactose, a deficiency of lactase and a syndrome of malabsorption of glucose and galactose.

Effect on the ability to drive transp. cf. and fur:

Against the background of therapy with allopurinol, development of such undesirable reactions as drowsiness, dizziness (vertigo) and ataxia was observed. These undesirable phenomena can affect the ability to drive vehicles and control mechanisms. Patients taking the drug Allopurinol-EGIS tablets should not drive vehicles and mechanisms until they are sure that allopurinol does not adversely affect the relevant abilities.

Form release / dosage:Tablets 100 mg, 300 mg.

Packaging:

Tablets of 100 mg: 50 tablets each in a bottle of brown glass with a PE cover with a control of the first opening and an accordion damper. 1 bottle in a cardboard box together with instructions for medical use.

Tablets of 300 mg: 30 tablets in brown glass bottle with a lid with a PE controls the first opening and the absorber accordion. 1 bottle in a cardboard pack together with instructions for medical use.

Storage conditions:

Allopurinol-EGIS tablets 100 mg: Store at a temperature of no higher than 30 ° C.

Allopurinol-EGIS tablets 300 mg: Store at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012684 / 01

Date of registration:31.08.2010 / 12.04.2016

Expiration Date:Unlimited

The owner of the registration certificate:Egis Pharmaceutical Plant OJSCEgis Pharmaceutical Plant OJSC Hungary

Manufacturer: & nbsp

EGIS PHARMACEUTICALS, Plc Hungary

Representation: & nbspEGIS ZAO Pharmaceutical Plant EGIS ZAO Pharmaceutical Plant Hungary

Information update date: & nbsp10.07.2017

Illustrated instructions

Instructions

Allopurinol-Aegis (Allopurinol-Egis)