ALLOPURINOL PILLS 300MG

Dosage and administration

Inside The drug should be taken 1 time / day after meals, drinking plenty of water. If the daily dose exceeds 300 mg or there are symptoms of intolerance from the gastrointestinal tract, then the dose should be divided into several doses.

Adult patients

In order to reduce the risk of side effects, it is recommended to use Allopurinol in the initial dose of 100 mg 1 time / day.If this dose is not enough to properly reduce the concentration of uric acid in the serum, then the daily dose of the drug can be gradually increased to achieve the desired effect. Special care should be taken when kidney function is impaired. With increasing doses of allopurinol every 1-3 weeks, it is necessary to determine the concentration of uric acid in serum.

When selecting the dose of the drug, it is recommended to use the following dosing regimens (depending on the selected dosing regimen, 100 mg or 300 mg pills are recommended).

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

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

Children and teenagers under the age of 15

The recommended dose for children from 3 to 10 years: 5-10 mg / kg / day. For low doses, 100 mg pills are used, which with the help of the risks can be divided into two equal doses of 50 mg. 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 exceptions are malignant oncological diseases (especially leukemia) and some enzymatic disorders (for example, Lesch-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 in the minimum dose that provides a sufficient reduction in serum uric acid concentration. Particular attention should be paid to the recommendations on the selection of the dose of the drug for patients with impaired renal function (see section "Special instructions").

Adverse effects

There are no current clinical data to determine 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 the incidence of side effects is based on a rough estimate, for most side effects there is no data to determine the frequency of their development.

The classification of undesirable reactions depending on the frequency of occurrence is as follows: very frequent (≥1 / 10), frequent (from ≥1 / 100 to <1/10), infrequent (from ≥1 / 1000 to <1/100), rare (from ≥1 / 10,000 to <1/1000), very rare (<1/10 000), frequency unknown (cannot be determined from the available data).

Observed in the post-registration period, adverse reactions associated with allopurinol therapy are rare or very rare. In the general population of patients in most cases are easy. The incidence of adverse events increases with impaired renal function and (or) liver.

Infections and parasitic diseases: very rare: furunculosis.

Violations of the blood system and lymphatic system: very rare - agranulocytosis, aplastic anemia, thrombocytopenia, granulocytosis, leukopenia, leukocytosis, eosinophilia and aplasia, affecting only erythrocytes; very rarely have there been reports of thrombocytopenia, agranulocytosis and aplastic anemia, especially in people with impaired renal and / or liver function, which emphasizes the need for special care in these groups of patients.

Immune system disorders: infrequent - hypersensitivity reactions; rare - severe hypersensitivity reactions, including skin reactions with epidermis detachment, fever, lymphadenopathy, arthralgia and (or) eosinophilia (including Stevens-Johnson syndrome and toxic epidermal necrolysis) (see section "Disorders of the skin and subcutaneous tissues "). Concomitant vasculitis or tissue reactions can have various manifestations, including hepatitis, kidney damage, acute cholangitis, xanthine stones and, in very rare cases, seizures. In addition, the development of anaphylactic shock was very rarely observed. With the development of severe adverse reactions, allopurinol therapy should be immediately stopped and not resumed.With delayed multiorgan hypersensitivity (known as drug hypersensitivity syndrome / DRESS /), the following symptoms may develop in various combinations: fever, skin rash, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly, changes in the effects of sephagia, cramping, changes in the effects of the masters. disappearing bile ducts (destruction or disappearance of intrahepatic bile ducts). With the development of such reactions during any period of treatment, Allopurinol-Egis should be immediately canceled and never renewed. Generalized hypersensitivity reactions developed in patients with impaired renal function and (or) liver. Such cases have sometimes been fatal; very rare - angioimmunoblastic lymphadenopathy. Angioimmunoblastic lymphadenopathy is very rarely diagnosed after a biopsy of the lymph nodes for generalized lymphadenopathy. Angioimmunoblastic lymphadenopathy is reversible and regresses after cessation of allopurinol therapy.

Metabolic and nutritional disorders: very rare - diabetes, hyperlipidemia.

Mental Disorders: very rare - depression.

Nervous system disorders: very rare - coma, paralysis, ataxia, neuropathy, paresthesia, drowsiness, headache, taste perversion.

Violations by the organ of vision: very rare - cataract, visual impairment, macular changes.

Disturbances from an organ of hearing and labyrinth frustration: very rare - vertigo.

Heart disorders: very rare - angina, bradycardia.

Vascular disorders: very rare - increased blood pressure.

Violations of the gastrointestinal tract: infrequent - vomiting, nausea, diarrhea. In earlier clinical studies, nausea and vomiting were observed, however, later observations confirmed that these reactions are not a clinically significant problem and can be avoided by prescribing allopurinol after a meal; very rare - recurrent bloody vomiting, steatorrhea, stomatitis, changes in the frequency of bowel movements; frequency unknown - abdominal pain.

Disorders of the liver and biliary tract: infrequent - asymptomatic increase in the concentration of liver enzymes (elevated levels of alkaline phosphatase and transaminases in serum); rare - hepatitis (including necrotic and granulomatous forms).

Liver dysfunction can develop without obvious signs of generalized hypersensitivity.

Violations of the skin and subcutaneous tissues: frequent - rash; rare - severe skin reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEH); very rare - angioedema, local medical rash, alopecia, hair discoloration.

In patients taking allopurinol, the most common adverse skin reactions. Against the background of drug therapy, these reactions can develop at any time. Skin reactions can occur with itching, maculopapular and scaly rashes. In other cases, purpura may develop. In rare cases, an exfoliative skin lesion is observed (SSD / TEN). With the development of such reactions, therapy with allopurinol must be stopped immediately. If the skin reaction is mild, then after the disappearance of these changes, you can resume taking allopurinol in a lower dose (for example, 50 mg / day). Subsequently, the dose can be gradually increased. When skin reactions recur, allopurinol should be stopped and no longer resumed, since further use of the drug may lead to more severe hypersensitivity reactions (see "Immune system disorders").

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

Disorders of the musculoskeletal and connective tissue: very rare - myalgia.

Kidney and urinary tract disorders: very rare - hematuria, renal failure, uremia; frequency is unknown - urolithiasis.

Disorders of the reproductive system and the breast: very rare - male infertility, erectile dysfunction, gynecomastia.

General disorders and disorders at the injection site: very rare - swelling, general malaise, general weakness, fever.

According to the available information, during the treatment 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, incl.not indicated in this manual, you should stop using the drug.

In the post-registration period, any information on possible adverse reactions is important, as these messages help to constantly monitor the safety of the drug. Health officials are required to report any suspicion of adverse reactions to local pharmacovigilance authorities.

Contraindications

- hypersensitivity to allopurinol or any of the excipients that make up the drug;

- liver failure;

- chronic renal failure (azotemia stage);

- primary hemochromatosis;

- asymptomatic hyperuricemia;

- acute attack of gout;

- children's age up to 3 years (taking into account the solid dosage form);

- pregnancy, breastfeeding period (see section “Use during pregnancy and breastfeeding”).

- patients with rare hereditary diseases, such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take the drug (the preparation includes lactose monohydrate).

Carefully: abnormal liver function, hypothyroidism, diabetes mellitus, arterial hypertension, concomitant use of ACE inhibitors or diuretics, children age (up to 15 years prescribed only during cytotoxic therapy of leukemia and other malignant diseases, as well as symptomatic treatment of enzyme disorders), old age.

Use during pregnancy and lactation

Pregnancy

Currently, there are insufficient data on the safety of therapy with allopurinol during pregnancy, although this drug was widely used for long periods without obvious adverse effects. Pregnant women should not take Allopurinol-Aegis tablets, except in cases where there is no less dangerous alternative treatment and the disease poses a greater risk to the mother and fetus than taking the drug.

Breastfeeding period

According to existing reports, allopurinol and oxypurinol are excreted in breast milk. In women taking 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.However, there is no information on the effect of allopurinol and its metabolites on breastfed infants. Thus, Allopurinol-Egis pills are not recommended during breastfeeding.

Application for violations of the liver

Use with caution in patients with impaired liver function.

Use of the drug is contraindicated in patients with hepatic insufficiency.

Application for violations of kidney function

The drug is contraindicated in patients with chronic renal insufficiency (azotemia stage).

Use in children

Use of the drug is contraindicated in children under the age of 3 years (taking into account the solid dosage form).

To use the drug with caution in children and adolescents under the age of 15 years (prescribed only during cytotoxic therapy of leukemia and other malignant diseases, as well as symptomatic treatment of enzyme disorders).

Use in elderly patients

To use the drug with caution in elderly patients.

special instructions

Syndrome of drug hypersensitivity, SJS and TEN

Allopurinol has been reported to develop life-threatening skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS / TEN). Patients should be informed about the symptoms of these reactions (progressive skin rash, often with blisters and mucosal lesions) and carefully monitor their development. The most common SSD / TEN develop in the first weeks of taking the drug. If there are signs and symptoms of SSD / TEN, Allopurinol-Egis should be immediately canceled and no longer prescribed!

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

Chronic renal failure

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

Allele HLA-B * 5801

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

Impaired liver and kidney function

When treating patients with impaired renal or liver function, the dose of allopurinol should be reduced. Patients receiving treatment for hypertension or heart failure (for example, patients taking diuretics or ACE inhibitors) may have a concomitant renal dysfunction, so allopurinol should be used with caution in this group of patients.

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

Acute attack of gout

Allopurinol should not be used until the acute relief of an acute attack of gout, since this can provoke an additional exacerbation of the disease.

Similarly, treatment with uricosuric drugs, the start of treatment with allopurinol can trigger an acute attack of gout. In order to avoid this complication, it is recommended to carry out prophylactic therapy with nonsteroidal anti-inflammatory drugs or colchicine for at least one month before the appointment of allopurinol. Detailed information about recommended doses, cautions 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 for the treatment of an attack it is necessary to prescribe a suitable non-steroidal anti-inflammatory agent.

Xanthine deposits

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

Congestion of uric acid

Adequate therapy with allopurinol can lead to the dissolution of large stones from the uric acid in the renal pelvis, however, the likelihood of these stones in the ureters is small.

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 hemochromatosis. Patients with hemochromatosis, as well as their blood relatives, should be prescribed allopurinol 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 rare hereditary intolerance to galactose, lactase deficiency and malabsorption syndrome of glucose and galactose.

Ability to drive vehicles

Allopurinol therapy was accompanied by the development of undesirable reactions such as drowsiness, dizziness (vertigo) and ataxia. These adverse events can affect the ability to drive and control machinery. Patients taking the drug Allopurinol-Egis pills should not drive vehicles and mechanisms until they are sure that allopurinol does not adversely affect the respective abilities.

Overdose

Symptoms: nausea, vomiting, diarrhea, and dizziness. Severe allopurinol overdose can lead to 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, especially on treatment with 6-mercaptopurine and (or) azathioprine.

Treatment: allopurinol specific antidote is unknown. Adequate hydration, supporting optimal diuresis, promotes the removal of allopurinol and its derivatives with urine. If clinically indicated, hemodialysis is performed.

Drug interaction

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 is combined with allopurinol, patients should be given 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.

Vidarabine (adenine arabinoside)

In the presence of allopurinol T1/2 Vidarabina increases. With the simultaneous use of these drugs, it is necessary to observe special vigilance regarding the enhanced toxic effects of therapy.

Salicylates and uricosuric drugs

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

Chlorpropamide

With the simultaneous use of allopurinol and chlorpropamid, in patients with impaired renal function, the risk of developing long-term hypoglycemia increases, since at the stage of canalicular excretion, allopurinol and chlorpropamid compete with each other.

Anticoagulants 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 can suppress the oxidation of phenytoin in the liver, however, the clinical significance of this interaction has not been established.

Theophylline

It is known that allopurinol inhibits theophylline metabolism. Such an interaction can be explained by the participation of xanthine oxidase in the theophylline biotransformation process in the human body. Serum theophylline concentration should be monitored at the beginning of concomitant therapy with allopurinol, as well as increasing the dose of the latter.

Ampicillin and Amoxicillin

Patients who received ampicillin or amoxicillin and allopurinol at the same time had an increased incidence of skin reactions compared with patients who did not receive similar concomitant therapy. The cause of this type of drug interaction has not been established. However, in 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 leukemias) and receiving allopurinol, an increased inhibition of bone marrow activity by cyclophosphamide and other cytotoxic drugs was observed. However, according to the results of controlled studies, in which patients receiving cyclophosphamide, doxorubicin, bleomycin, procarbazine and (or) mechlorethamine (chlormethine hydrochloride) took part, concomitant therapy with allopurinol did not increase the toxic effect of these cytotoxic drugs.

Cyclosporine

According to some reports, plasma plasma cyclosporine levels may increase with concomitant therapy with allopurinol. With the simultaneous use of these drugs it is necessary to consider the possibility of increasing the toxicity of cyclosporine.

Didanosine

In healthy volunteers and HIV-infected patients receiving didanosine, with the background of concomitant therapy with allopurinol (300 mg / day), an increase in C was observedmax and AUC of didanosine approximately 2 times. T1/2 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 lower the dose of didanosine and carefully monitor the patient’s condition.

ACE Inhibitors

The simultaneous use of an ACE inhibitor with allopurinol is accompanied by an increased risk of leukopenia, so these drugs should be combined with caution.