Milurite (Allopurinol-Egis) pills 100mg, 50pcs

Composition

For 1 tablet:

Active ingredient:

allopurinol 100 mg;

excipients:

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

Pharmacological action

Pharmacotherapy group: anti-gouty agent-xanthine oxidase inhibitor

ATX CODE: M04AA01

PHARMACOLOGICAL PROPERTIES

Pharmacodynamics :

Allopurinol is a structural analog of hypoxanthine. Allopurinol and 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, both in the blood serum and in the urine. Thus, it prevents the deposition of uric acid crystals in the tissues and (or) promotes their dissolution.

In addition to inhibiting purine catabolism in some (but not all) hyperuricemic patients, large amounts of xanthine and hypoxanthine are available for the re-formation of purine bases, which leads to inhibition of de novo purine biosynthesis via a feedback mechanism mediated by inhibition of the enzyme hypoxanthine-guanine phosphoribosyl transferase. Other metabolites of allopurinol are allopurinol-riboside and oxypurinol-7 riboside.

Pharmacokinetics:

Absorption

Allopurinol is active when administered orally. It is rapidly absorbed from the upper gastrointestinal tract (GIT). According to pharmacokinetic studies, allopurinol is detected in the blood within 30-60 minutes after use. The bioavailability of allopurinol varies from 67% to 90%. The maximum concentration of the drug in blood plasma (TC_max) is usually recorded approximately 1.5 hours after oral use.

Then the concentration of allopurinol decreases rapidly. 6 hours after use, only a trace concentration of the drug is detected in the blood plasma. The maximum concentration (cmax) of the active metabolite oxypurinol is usually recorded 3-5 hours after oral use of allopurinol. The concentration of oxypurinol in the blood plasma decreases much more slowly.

Distribution

Allopurinol is almost not bound to plasma proteins, so changes in the degree of protein binding should not significantly affect the clearance of the drug. The apparent volume of distribution₍vd) of allopurinol is approximately 1.6 liters / kg, which indicates a fairly pronounced absorption of the drug by tissues. The concentration 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 xanthine oxidase activity is recorded.

Biotransformation

Under the action of xanthine oxidase and aldehyde oxidase, allopurinol is metabolized to form oxypurinol. Oxypurinol inhibits xanthine oxidase activity. However, oxypurinol is not as potent a xanthine oxidase inhibitor as allopurinol, but its half-life (_half-life) is significantly longer. Due to these properties, after taking a single daily dose of allopurinol, effective suppression of xanthine oxidase activity is maintained for 24 hours.

In patients with normal renal function, the concentration of oxypurinol in the blood plasma slowly increases until the equilibrium concentration is reached. After taking allopurinol at a dose of 300 mg per day, the concentration of allopurinol in blood plasma is usually 5-10 mg/l. Other metabolites of allopurinol include allopurinol-riboside and oxypurinol-7-riboside.

Deduction

Approximately 20% of allopurinol taken per os is excreted unchanged through the intestine. 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 by the kidneys in the form of oxypurinol. Oxypurinol is excreted unchanged by the kidneys, but due to 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 likely due to differences in the structure of studies and / or creatinine clearance (CC) in patients.

Patients with impaired renal function

In patients with impaired renal function, the elimination of allopurinol and oxypurinol can significantly slow down, which leads to an increase in the concentration of these compounds in the blood plasma during long-term therapy. 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 blood plasma reached approximately 30 mg/l. Such a concentration of oxypurinol can be determined in patients with normal renal function on the background of therapy with allopurinol at a dose of 600 mg per day. Therefore, when treating 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. The exception is patients with concomitant kidney disease.

Indications

Adults:

·  All types of hyperuricemia that cannot be controlled by diet, including secondary hyperuricemia of various origins, and clinical complications of hyperuricemia, in particular, severe gout, urate nephropathy, as well as the dissolution and prevention of uric acid crystals (kidney stones).

* Treatment of recurrent, mixed calcium oxalate crystals, accompanied by hyperuricemia, if the use of various liquids, diet and similar measures do not have an effect.

Children and teenagers:

·  Secondary hyperuricemia of various origins.

·  Uric acid-induced nephropathy in the treatment of leukemia.

·  Congenital enzyme deficiency, Lesch-Nihan syndrome (complete or partial hypoxanthine-guanine phosphoribosyltransferase deficiency) and adenine phosphoribosyltransferase deficiency.

Use during pregnancy and lactation

Pregnancy

Currently, there are insufficient data on the safety of allopurinol therapy during pregnancy, although this drug has been widely used for many years without obvious adverse effects. Pregnant women should not take Milurit tablets, unless there is no less dangerous alternative treatment and the disease poses a greater risk to the mother and fetus than taking the drug.

Breast-feeding period

Allopurinol and its metabolite oxypurinol are excreted in human breast milk. The drug Milurit ® tablets is not recommended during breastfeeding. In women taking allopurinol at 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. However, there is no data available on the effects of allopurinol and its metabolites on breastfed infants.

Contraindications

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

Liver failure, chronic renal failure (azotemia stage), acute gout attack, children under 3 years of age (including solid dosage form)

Pregnancy and lactation (see section “Use during pregnancy and lactation”).

Patients with rare hereditary diseases such as lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome (tablets contain lactose monohydrate – only for 100 mg tablets.

With caution

Violations of liver function, hypothyroidism, diabetes mellitus, arterial hypertension, primary hemochromatosis, concomitant use of angiotensin-converting enzyme inhibitors (ACE) or diuretics, children’s age (under 15 years old are prescribed only during cytostatic therapy of leukemias and malignant diseases etc., as well as symptomatic treatment of enzyme disorders), older age, impaired renal function (impaired renal function may lead to a delay of the drug and its metabolites with consequent lengthening of the T _½ of these compounds from plasma).

Side effects

There are no current clinical data to determine the frequency of side effects. Their frequency may vary depending on the dose and whether the drug was prescribed as monotherapy or in combination with other drugs.

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

The classification of adverse reactions depending on the frequency of occurrence is as follows:

very frequent (>1/10), >

frequent (>1/100 to ><1/10),

infrequent (>1/1000 to ><1/100),

rare (>1/10 000 to >< 1/1000),

very rare (<1/10 000),

frequency unknown (cannot be determined based on available data).

Post-marketing adverse reactions associated with allopurinol therapy are rare or very rare. In the general patient population, most cases are mild in nature. The frequency of adverse events increases with impaired renal and / or liver function.

Infections and parasitic diseases:

Very rare: furunculosis.

Disorders of the blood and lymphatic system:

Very rare: agranulocytosis, aplastic anemia, thrombocytopenia, granulocytosis, leukopenia, leukocytosis, eosinophilia and aplasia affecting only red blood cells.

Thrombocytopenia, agranulocytosis, and aplastic anemia have been reported very rarely, especially in individuals with impaired renal and/or hepatic function, which underscores the need for special caution in these groups of patients.

Immune system disorders:

Infrequent: hypersensitivity reactions; severe hypersensitivity reactions, including skin reactions with epidermal detachment, fever, lymphadenopathy, arthralgia and /or eosinophilia (including Stevens-Johnson syndrome (SDS) and toxic epidermal necrolysis (TEN)) (see the section “Skin and subcutaneous tissue disorders”). Concomitant vasculitis or tissue reactions can have a variety of manifestations, including hepatitis, kidney damage, acute cholangitis, xanthine calculi, and, in very rare cases, seizures. In addition, the development of anaphylactic shock was very rare. If severe adverse reactions develop, allopurinol therapy should be stopped immediately and not resumed. Delayed multi-organ hypersensitivity (known as drug-induced hypersensitivity syndrome) may develop the following symptoms in various 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). Other organs may be affected (such as the liver, lungs, kidneys, pancreas, myocardium, and large intestine). If such reactions occur during any period of treatment, Milurit should be discontinued immediately and never resumed. Patients with hypersensitivity syndrome and SSD/TEN should not start taking the drug again. Corticosteroids may be useful in the treatment of skin hypersensitivity reactions.

Generalized hypersensitivity reactions developed in patients with impaired renal and / or hepatic function. Such cases were sometimes fatal.

Very rare: angioimmunoblastic T-cell lymphoma.

Angioimmunoblastic T-cell lymphoma was very rarely diagnosed after a lymph node biopsy for generalized lymphadenopathy. Angioimmunoblastic lymphadenopathy is reversible and regresses after discontinuation of allopurinol therapy.

Metabolic and nutritional disorders:

Very rare: diabetes mellitus, hyperlipidemia.

Mental disorders:

Very rare: depression.

Nervous system disorders:

Very rare: coma, paralysis, ataxia, peripheral neuropathy, paresthesia, drowsiness, headache, dysgeusia.

Visual disturbances:

Very rare: cataracts, visual disturbances, maculopathy.

Hearing disorders and labyrinth disorders:

Very rare: vertigo (vertigo).

Cardiac disorders:

Very rare: angina pectoris, bradycardia.

Vascular disorders:

Very rare: high blood pressure.

Disorders of the gastrointestinal tract:

Infrequent: vomiting, nausea, diarrhea;

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

Very rare: bloody vomiting, steatorrhea, stomatitis, changes in the frequency of bowel movements and stool patterns;

Frequency unknown: abdominal pain.

Liver and biliary tract disorders:

Infrequent: asymptomatic increase in the activity of liver enzymes (increased activity of alkaline phosphatase and transaminases in blood serum);

Rare: hepatitis (including necrotic and granulomatous forms).

Liver function disorders can develop without obvious signs of generalized hypersensitivity.

Skin and subcutaneous tissue disorders:

Common: rash.

Rare: severe skin reactions: SSD and TEN

Skin reactions are the most common type of reaction, and they can develop at any time during treatment. They can be itchy, maculopapular, sometimes scaly or purplish rashes, and in rare cases exfoliative lesions such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SSD/TEN). The greatest risk of developing SS and TEN or other serious hypersensitivity reactions is noted during the first weeks of allopurinol use. The best treatment results for these reactions are achieved with early diagnosis and immediate discontinuation of all suspected medications. If such a reaction develops, Milurit® should be discontinued immediately. When returning to normal after mild reactions, the use of allopurinol can be resumed at a low dose (such as 50 mg/day), which can be gradually increased. The HLA-B*5801 allele has been shown to be associated with the risk of allopurinol-dependent hypersensitivity syndrome and SS/TEN. If a skin reaction occurs repeatedly, allopurinol should be discontinued immediately and permanently, taking into account the possibility of developing more severe hypersensitivity (see the section “Immune system disorders”). If the presence of SS/TEN or other serious hypersensitivity reactions cannot be excluded, DO NOT resume the use of allopurinol, due to the possibility of developing a severe or even fatal reaction. The basis for making a decision is the presence of a clinical diagnosis of SSD / TEN. If such reactions occur at any time during treatment, allopurinol should be discontinued immediately and permanently.

Very rare: angioedema, local drug rash, alopecia, hair discoloration.

According to the available data, angioedema developed in isolation during allopurinol therapy, as well as in combination with symptoms of a generalized hypersensitivity reaction.

Musculoskeletal and connective tissue disorders:

Very rare: myalgia.

Kidney and urinary tract disorders:

Rare: Urolithiasis

Very rare: hematuria, azotemia;

Disorders of 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, asthenia, fever.

According to available data, fever developed both in isolation and in combination with symptoms of a generalized hypersensitivity reaction during allopurinol therapy (see “Disorders of the immune system”).

Influence on the results of laboratory and instrumental studies

Frequent: increased thyroid-stimulating hormone (TSH)levels

The increase in TSH levels observed in the corresponding studies did not affect T4 levels and did not indicate the occurrence of subclinical hypothyroidism.

Reports of possible adverse reactions

Providing data on suspected adverse drug reactions is very important, allowing for continuous monitoring of the risk / benefit ratio of the drug. Health professionals should provide information about any suspected adverse reactions to the contacts listed at the end of the instructions, as well as through the national information collection system.

Interaction

of 6-mercaptopurine and azathioprine

Azathioprine is metabolized to form 6-mercaptopurine, which is inactivated by the enzyme xanthine oxidase. In cases where 6-mercaptopurine or azathioprine therapy is combined with allopurinol, patients should be prescribed only one-quarter of the usual dose of 6-mercaptopurine or azathioprine, since inhibition of xanthine oxidase activity increases the duration of action of these compounds. If the dose of these drugs is not reduced, their serum concentrations can reach toxic levels.

Vidarabine (Adenine arabinoside)

In the presence of allopurinol, the elimination half-life of vidarabine increases. With the simultaneous use of these drugs, special caution should be observed regarding the increased toxic effects of therapy.

Salicylates and uricosuric agents

The main active metabolite of allopurinol is oxypurinol, which is excreted by the kidneys in a similar way to uric acid salts. Therefore, drugs with uricosuric activity, such as probenecid or high doses of salicylates, may increase the excretion of oxypurinol. In turn, increased elimination of oxypurinol is accompanied by a decrease in the therapeutic activity of allopurinol, however, the significance of this type of interaction should be evaluated individually in each case.

Chlorpropamide

Concomitant use of allopurinol and chlorpropamide increases the risk of long-term hypoglycemia in patients with impaired renal function, since allopurinol and chlorpropamide compete with each other during the tubular excretion stage.

Anticoagulants coumarin derivatives

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

Phenytoin

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

Theophylline

Allopurinol is known to inhibit theophylline metabolism. This 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 the blood serum should be monitored at the beginning of concomitant therapy with allopurinol, as well as with an increase in the dose of the latter.

Ampicillin and amoxicillin

Patients treated with ampicillin or amoxicillin and allopurinol at the same time had an increased incidence of skin reactions compared to patients who did not receive such concomitant therapy. The cause of this type of drug interaction has not been established. However, patients receiving allopurinol are advised to take other antibacterial drugs instead of ampicillin and amoxicillin.

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

When allopurinol is co-administered with cytostatic drugs (such as cyclophosphamide, doxorubicin, bleomycin, procarbazine, and alkyl halides), blood dyscrasias develop more frequently than when these drugs are used separately.

The number of blood cells should be counted regularly.

Cyclosporine

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

Aluminum Hydroxide

When allopurinol is co-administered with aluminum hydroxide, the effect of allopurinol may decrease. You should take a break of at least 3 hours between taking both medications.

Didanosine

In healthy volunteers and patients infected with the human immunodeficiency virus receiving didanosine, concomitant therapy with allopurinol (300 mg per day) increased cmax (maximum concentration of the drug in blood plasma) and AUC (area under the concentration-time curve) of didanosine 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, it may be necessary to reduce the dose of didanosine and carefully monitor the patient’s condition.

ACE inhibitors

Concomitant use of ACE inhibitors with allopurinol is associated with an increased risk of leukopenia, so these drugs should be combined with caution.

An increased risk of hypersensitivity has been reported when allopurinol was used with ACE inhibitors, especially in patients with renal insufficiency.

Concomitant use of allopurinol with captopril may increase the risk of skin reactions, especially in patients with chronic renal failure.

Diuretics

An interaction between allopurinol and furosemide has been reported, leading to an increase in serum urate levels and plasma oxypurinol concentrations.

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

How to take, course of use and dosage

Inside. The drug should be taken once a day after meals, washed down with plenty of water. It is well tolerated, especially after a meal. If the daily dose exceeds 300 mg or there are undesirable reactions from the gastrointestinal tract, then the dose should be divided into several doses.

Using this method, the tablets can be divided into two identical doses.

Adult patients

In order to reduce the risk of side effects, it is recommended to use allopurinol at an initial dose of 100 mg once a day. If this dose is not sufficient to properly reduce the concentration of uric acid in the blood serum, then the daily dose of the drug can be gradually increased.

Special care should be taken if renal function is impaired. The recommended dose of the drug is:

100-200 mg per day in mild cases;

300-600 mg per day in moderate cases;

700-900 mg per day in severe cases.

If the dose calculation is based on the patient’s body weight, then the dose of allopurinol should be from 2 to 10 mg / kg / day.

Children and teenagers under 15 years of age

Recommended dose: 10-20 mg / kg / day. For low doses,100 mg tablets are used, which can be divided into two identical doses of 50 mg with the help of the drug. The daily dose of the drug should not exceed 400 mg in three doses per day.

Allopurinol is rarely used in pediatric practice. The exceptions are malignant oncological diseases (especially leukemias) and some enzymatic disorders (for example, Lesh-Nyhan syndrome).

Elderly patients

Since there are no specific data on the use of allopurinol in the elderly population, for the treatment of such patients, the drug should be used at a minimum dose that provides a sufficient decrease in the concentration of uric acid in the blood serum. Special attention should be paid to the recommendations for selecting the dose of the drug for patients with impaired renal function (see section Special instructions).

Impaired renal function

Since allopurinol and its metabolites are eliminated 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 extension of the half-life of these compounds from the blood plasma.

The following scheme can serve as a guideline for dose adjustment in patients with renal insufficiency:

Creatinine clearance	Daily dose
>20 ml / min>	Normal dose
10-20 ml / min	100-200 mg / day
<10 ml / min	100 mg / day or prolongation of dosage intervals

In severe renal insufficiency, it is recommended to use allopurinol at a dose below 100 mg per day, or use single doses of 100 mg at intervals of more than one day.

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

Allopurinol and its derivatives are removed from the body by hemodialysis. If hemodialysis sessions are performed 2-3 times a week, it is advisable to determine the need to switch to an alternative therapy regimen – taking 300-400 mg of allopurinol immediately after the end of the hemodialysis session (the drug is not taken between hemodialysis sessions).

In patients with impaired renal function, allopurinol should be combined with thiazide diuretics with extreme caution. Allopurinol should be administered in the lowest effective doses with careful monitoring of renal function.

Liver function disorders

In case of impaired liver function, 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 associated with increased uric acid metabolism (for example, tumor diseases, Lesch-Nyhan syndrome)

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

If the impaired renal function is caused by the development of acute uric acid nephropathy or other renal pathology, then treatment should be continued in accordance with the recommendations presented in the section “Impaired renal function”.

These measures can reduce the risk of accumulation of xanthine and uric acid, which complicates the course of the disease.

Monitoring recommendations

To adjust the dose of the drug, it is necessary to assess the concentration of uric acid salts in the blood serum, as well as the level of uric acid and urates in the urine at optimal intervals.

Recommendations for dose selection in case of skin reactions

In case of skin reactions, the use of allopurinol should be stopped immediately. When returning to normal after mild reactions, allopurinol may be resumed at a low dose (such as 50 mg/day) after careful consideration of the risks. After that, the dose can be gradually increased if skin reactions and other possible adverse events are observed. If the rash reappears, the use of allopurinol should be permanently discontinued, taking into account the possibility of more severe hypersensitivity reactions.

Overdose

A case of oral use of allopurinol at a dose of up to 22.5 g without adverse events is described.

Symptoms of overdose: nausea, vomiting, diarrhea and dizziness were observed in the patient. who has taken 20 g of allopurinol.

Severe overdose of allopurinol can lead to significant inhibition of xanthine oxidase activity.By itself, this effect should not be accompanied by undesirable reactions. The exception is the effect on concomitant therapy, especially on treatment with 6-mercaptopurine and / or azathioprine.

Treatment:

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

Description

Tablets of 100 mg: Round flat tablets of white or grayish-white color, with a chamfer, with a risk on one and with the inscription E 351 on the other side, without or almost odorless.

Special instructions

Drug hypersensitivity syndrome, SSD and TEN (Stevens-Johnson syndrome and toxic epidermal necrolysis)

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 serve as a basis for making appropriate decisions. Treatment with Milurit should be discontinued immediately if a skin rash or other hypersensitivity reaction occurs. Do not resume therapy in patients with hypersensitivity syndrome and SSD/TEN. Glucocorticosteroids can be used to treat skin reactions with hypersensitivity.

HLA-B allele*5801

It was found that the presence of the HLA-B*5801 allele is associated with the development of hypersensitivity syndrome to allopurinol and SSD/TEN. The frequency of the HLA-B*5801 allele is different in different ethnic groups and can reach 20% in the Han Chinese population,8-15% in Thais, about 12% in Koreans, and 1-2% in Japanese and Europeans.

Consideration should be given to screening for the HLA-B*5801 allele before starting treatment with allopurinol in subgroups of patients with a known high prevalence of the HLA-B*5801 allele. Chronic kidney disease may further increase this risk in these patients. If there is no possibility of genotyping in Han Chinese, Thai or Korean patients, then allopurinol should be prescribed only if the benefit of treatment outweighs the possible increased risk. The use of genotyping for decision – making on allopurinol therapy in other patient groups has not been studied.

If it is known that the patient is a carrier of the HLA-B*5801 allele (especially in Han Chinese, Thais, Koreans) allopurinol therapy should not be initiated unless there are no other possible adequate treatment options.

Hypersensitivity syndrome and SDS/TEN should be monitored very closely, and patients should be informed about the need to immediately discontinue treatment at the first appearance of such symptoms.

Patients who lack the HLA-B*5801 allele may also develop SD/TEN, regardless of their ethnic origin.

Chronic renal failure

Patients with chronic renal failure may be at an increased risk of developing hypersensitivity reactions, including allopurinol-related SS/TEN, with concomitant use of diuretics, especially thiazide diuretics. Special caution is required regarding signs of hypersensitivity syndrome or SS/TEN, and patients should be informed of the need to immediately and permanently discontinue allopurinol treatment at the first onset of symptoms.

Impaired liver or kidney function

In patients with impaired liver or kidney function, reduced doses of allopurinol should be used. Patients receiving treatment for hypertension or heart failure, such as with diuretics or ACE inhibitors, may experience a slight decrease in renal function. In such patients, allopurinol should be used with caution.

Asymptomatic hyperuricemia

Allopurinol is not indicated in all cases of hyperuricemia that occurs without clinical manifestations. In such cases, improvement in patients ‘ condition can be achieved through changes in diet and fluid intake, along with eliminating the underlying cause of hyperuricemia.

Acute attack of gout

Do not start using allopurinol until the acute attack of gout is completely stopped, since this can provoke an additional exacerbation of the disease.

Similar to uricosuric therapy, start treatment with Milurit® it can also trigger an acute attack of gout. In order to avoid this complication, it is recommended to conduct preventive therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) or colchicine for at least one month before prescribing allopurinol. Detailed information on recommended doses, warnings, and precautions can be found in the relevant literature.

If an acute attack of gout develops during therapy with allopurinol, then the drug should be continued at the same dose, and a suitable NSAID should be prescribed to treat the attack.

Azathioprine or 6-mercaptopurine

Allopurinol should not be prescribed to patients receiving treatment with azathioprine or 6-mercaptopurine, unless the dose of these drugs is reduced to 25% of the originally prescribed dose.

Xanthine Deposition

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

Effect on uric acid concretions

Adequate therapy with allopurinol can lead to the dissolution of large uric acid stones in the renal pelvis, with a long-term probability of their entry into the ureters.

In the treatment of gouty kidney damage and urate stones, the daily volume of urine excreted should be at least 2 liters, and the pH value of urine should be in the range of 6.4-6.8.

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 the reduction and elimination of iron deposited in the liver. There are no studies demonstrating the safety of allopurinol therapy in the population of patients with hemochromatosis. Patients with hemochromatosis, as well as their blood relatives, should be prescribed allopurinol with caution.

Thyroid disorders

Elevated TSH (thyroid-stimulating hormone) values (>5.5 MIU / ml) were observed in patients who received allopurinol for a long time (5.8%) as part of a long-term open-label additional clinical study. Caution should be exercised when using allopurinol in patients with impaired thyroid function.

Lactose

Each 100 mg tablet of Milurit® contains 50 mg of lactose. Therefore, this drug should not be taken by patients with lactose intolerance, lactase deficiency and glucose-galactose malabsorption syndrome.

Influence on the ability to drive vehicles and mechanisms

Adverse reactions such as drowsiness, vertigo (vertigo), and ataxia were observed during allopurinol therapy. These undesirable effects can affect the ability to drive vehicles and work with mechanisms. Patients taking the drug Milurit ® tablets should not drive vehicles and mechanisms until they are sure that allopurinol does not adversely affect their respective abilities.

Storage conditions

Keep out of reach of children at a temperature not exceeding 30 ° C.

Shelf

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

Active ingredient

Allopurinol

Conditions of release from pharmacies

By prescription

Dosage form

Tablets