Allopurinol-KV tablets 300 mg blister No. 30

Instructions for use Allopurinol-KV tablets 300 mg blister No. 30

Composition

active ingredient: allopurinol;

1 tablet contains allopurinol 300 mg;

excipients: powdered cellulose, microcrystalline cellulose, povidone, polyethylene glycol, crospovidone, talc, colloidal anhydrous silicon dioxide, magnesium stearate.

Dosage form

Pills.

Main physicochemical properties:

for 300 mg tablets: white or almost white tablets, flat-cylindrical in shape with a bevel and a score on one side.

Pharmacotherapeutic group

Drugs that inhibit the formation of uric acid.

ATX code M04A A01.

Pharmacological properties

Pharmacodynamics

Allopurinol and its main metabolite oxypurinol disrupt the synthesis of uric acid, exhibit urostatic properties, which are based mainly on the ability to inhibit the enzyme xanthine oxidase, which catalyzes the oxidation of hypoxanthine to xanthine and xanthine to uric acid, which leads to a decrease in the concentration of uric acid and promotes the dissolution of urates.

Pharmacokinetics

Allopurinol is rapidly absorbed from the upper gastrointestinal tract. After oral administration, allopurinol is detected in the blood plasma within 30-60 minutes. The bioavailability of the drug is 67-90%.

Peak plasma concentrations of allopurinol and its metabolite oxypurinol are reached 1.5 hours and 3-5 hours after administration, respectively. Allopurinol is almost not bound to plasma proteins. Its volume of distribution is approximately 1.3 l/kg.

Allopurinol is rapidly (plasma half-life 1-2 hours) oxidized by xanthine oxidase and aldehyde oxidase to oxypurinol, which is also a potent inhibitor of xanthine oxidase, but the half-life of the metabolite can be as long as 13 to 30 hours. Given the long half-life of oxypurinol, gradual accumulation may occur at the beginning of therapy until steady-state plasma concentrations are reached. In patients with normal renal function, the average plasma concentration of oxypurinol is usually 5-10 mg/l after a single dose of 300 mg allopurinol.

Allopurinol is excreted primarily by the kidneys, with less than 10% of the drug excreted unchanged. Approximately 20% of allopurinol is excreted in the feces. Oxypurinol is excreted unchanged in the urine after tubular reabsorption.

Impaired renal function leads to a prolongation of the half-life of oxypurinol, therefore, patients with renal insufficiency should follow the dosage recommendations.

Indication

Adults. Treatment of all forms of hyperuricemia not controlled by diet, with serum uric acid levels of 535 μmol/l (9 mg/100 ml) and above; diseases caused by increased serum uric acid levels, including gout, urate nephropathy and urate urolithiasis; secondary hyperuricemia of various origins; primary and secondary hyperuricemia in various hemoblastoses (acute leukemia, chronic myelogenous leukemia, lymphosarcoma).

Tablets of 300 mg

Children and adolescents weighing ≥ 45 kg:

secondary hyperuricemia of various origins; urate nephropathy resulting from leukemia treatment; congenital enzymatic deficiency, in particular Lesch-Nyhan syndrome (partial or complete deficiency of hypoxanthine-guanine-phosphoribosyltransferase) and adenine-phosphoribosyltransferase deficiency.

Contraindication

Hypersensitivity to allopurinol or to any of the components of the drug. Severe renal dysfunction (creatinine clearance less than 2 ml/min) and liver. With creatinine clearance less than 20 ml/min, 300 mg tablets are not used.

Interaction with other medicinal products and other types of interactions

6-Mercaptopurine and azathioprine. When allopurinol is taken simultaneously with 6-mercaptopurine or azathioprine, the doses of the latter should be reduced by 25%, since the metabolism of these drugs is slowed down due to inhibition of xanthine oxidase, and their effect is prolonged.

Vidarabine (adenine arabinoside). The simultaneous use of allopurinol with vidarabine prolongs the half-life of the latter from blood plasma, so this combination should be used with caution to avoid possible increased toxic effects.

Salicylates and drugs that promote the excretion of uric acid. The effectiveness of allopurinol may be reduced when used concomitantly with drugs that can excrete uric acid (sulfinpyrazone, probenecid, benzbromarone or salicylates).

Allopurinol slows down the elimination of probenecid.

Chlorpropamide. In case of impaired renal function, especially when used simultaneously with allopurinol, the hypoglycemic effect of chlorpropamide may be prolonged, requiring a dose reduction.

Anticoagulants (coumarin derivatives). The effect of warfarin and other anticoagulants - coumarin derivatives may be enhanced, therefore more frequent monitoring of blood coagulation is required, as well as a reduction in the dose of anticoagulants.

Theophylline, caffeine. In high doses, allopurinol inhibits the metabolism and increases the plasma concentration of theophylline and caffeine. At the beginning of treatment with allopurinol or when increasing its dose, it is necessary to monitor the level of theophylline in the blood plasma.

Ampicillin/amoxicillin: There is a risk of allergic skin reactions (exanthema) when allopurinol is used concomitantly with ampicillin or amoxicillin, therefore patients taking allopurinol should be given other antibiotics.

Cytostatics. When allopurinol is used with cytostatics (cyclophosphamide, doxorubicin, bleomycin, procarbazine, mechlorethamine), increased bone marrow suppression has been observed, therefore blood counts should be monitored at short intervals in such patients.

Cyclosporine: When used with allopurinol, cyclosporine plasma concentrations may increase and its toxicity may increase.

Didanosine: Concomitant use with allopurinol is not recommended as an almost two-fold increase in Cmax and AUC of didanosine has been observed.

Captopril: Concomitant use of allopurinol and captopril may increase the risk of skin reactions, especially in chronic kidney disease.

Application features

If hypersensitivity reactions occur, including Stevens-Johnson syndrome, toxic epidermal necrolysis, maculopapular exanthema, allopurinol should be discontinued immediately and not re-administered.

The presence of the HLA-B*5801 allele (a genetic marker) in patients treated with allopurinol is associated with an increased risk of hypersensitivity reactions. The frequency of this genetic marker varies considerably between ethnic groups (20% of Han Chinese, 12% of Koreans, 1-2% of Japanese and Caucasians). If a patient is known to have the HLA-B*5801 allele, allopurinol should only be considered if the expected benefits of treatment outweigh the potential risks.

Such patients should be informed of the need to discontinue treatment at the first symptoms of hypersensitivity syndrome.

Allopurinol is not recommended if the plasma uric acid level is below 535 μmol/L (9 mg/100 mL), following dietary recommendations and in the absence of renal impairment. Avoid foods high in purine (e.g. offal: kidneys, brain, liver, heart and tongue; meat broths and alcohol, especially beer).

If hypersensitivity reactions (e.g. eczema) occur, allopurinol should be discontinued immediately.

In case of impaired renal or hepatic function or previously diagnosed disorders of hematopoiesis, particularly careful medical supervision is required. For patients with impaired renal or hepatic function, the appropriate dosage recommendations should be taken into account. Allopurinol should be used with particular caution in patients suffering from arterial hypertension or heart failure and receiving ACE inhibitors or diuretics.

When treating gout and urolithiasis, the volume of urine excreted should be at least 2 liters per day.

To prevent an increase in serum or urine uric acid concentration, which may occur during radiotherapy or chemotherapy of neoplasms, as well as in Lesch-Nyhan syndrome, in addition to allopurinol, large amounts of fluid should be consumed to maintain adequate diuresis. In addition, to improve the excretion of uric acid, alkalinization of the urine, which leads to the dissolution of urates/uric acid, can be performed.

If urate nephropathy or other pathological changes have already caused renal dysfunction, the dose should be adjusted according to renal function indicators.

In the presence of acute gout attacks, treatment with allopurinol should not be started until they have completely disappeared. At the beginning of treatment with allopurinol, acute gout attacks may be aggravated by the mobilization of large amounts of uric acid. Therefore, during the first 4 weeks of treatment, concomitant use of analgesics or colchicine is necessary.

In the presence of large uric acid stones in the renal pelvis, it cannot be ruled out that during treatment with allopurinol, some of the stones may dissolve and enter the bladder, which may subsequently cause obstruction of the ureter.

Ability to influence reaction speed when driving vehicles or other mechanisms

Until the individual response to allopurinol is determined, caution should be exercised when driving or operating machinery due to the possibility of dizziness, drowsiness, and ataxia.

Use during pregnancy or breastfeeding

There are insufficient data on the use of allopurinol during pregnancy. Since allopurinol affects purine metabolism and the potential risk to humans is unknown, allopurinol is not recommended for use during pregnancy.

Allopurinol passes into breast milk, so the drug should not be taken during breastfeeding.

Method of administration and doses

The daily dose is determined individually depending on the level of uric acid in the blood serum. To reduce the risk of adverse reactions, treatment should be started with 100 mg of allopurinol once a day and the dosage should be increased only if the level of uric acid in the blood serum is not sufficiently reduced.

The following dosage regimens are recommended:

for mild conditions – from 100 to 200 mg per day;

for moderately severe conditions – from 300 to 600 mg per day;

in severe conditions: from 700 to 900 mg per day.

If the daily dose of allopurinol exceeds 300 mg, it should be divided into several doses (no more than 300 mg at a time).

When calculating the dose of the drug based on the patient's body weight, doses of 2-10 mg/kg of body weight per day should be used.

Children and adolescents weighing ≥ 15 kg

The daily dose of allopurinol is 10 mg/kg body weight, divided into 3 doses.

The maximum daily dose is 400 mg. Use 100 mg tablets.

Children and adolescents weighing ≥ 45 kg

The daily dose of allopurinol is 10 mg/kg body weight, divided into 3 doses.

The maximum daily dose is 400 mg.

Elderly patients

In the absence of specific data on the use of allopurinol in this category of patients, it is recommended to use the lowest therapeutically justified doses. The possibility of impaired renal function in elderly patients should be taken into account.

Patients with renal failure.

Since allopurinol and its metabolites are excreted by the kidneys, overdose is possible if their function is impaired if the dose has not been selected properly.

In severe renal impairment, the maximum daily dose is 100 mg. A single dose of 100 mg may be administered at intervals of more than 24 hours (every 2-3 days).

If it is necessary to increase the dose, the serum level of oxypurinol should be monitored, which should not exceed 15.2 μg/ml.

During hemodialysis, after each session (2-3 times a week), use 300-400 mg of allopurinol.

Patients with liver dysfunction

Patients with impaired liver function should be prescribed lower doses. At the beginning of treatment, it is recommended to periodically monitor liver function tests. Tablets of 300 mg should not be prescribed to these patients due to the high content of the active substance. The tablets should be taken after meals, without chewing, with plenty of liquid. The duration of treatment depends on the course of the underlying disease. In order to prevent the formation of oxalate and urate stones and in primary hyperuricemia and gout, long-term therapy is required in most cases. In secondary hyperuricemia, short-term treatment is recommended in accordance with the duration of the increase in uric acid levels.

Children

The drug should not be used in children weighing < 15 kg. The 300 mg tablets should not be used in children weighing < 45 kg.

Overdose

Symptoms. After taking a single dose of 20 g, one patient experienced symptoms such as nausea, vomiting, diarrhea, and dizziness. In another patient, a dose of 22.5 g of allopurinol did not cause any undesirable effects. After prolonged intake of 200-400 mg of allopurinol per day in patients with impaired renal function, severe symptoms of intoxication (skin reactions, fever, hepatitis, eosinophilia, and exacerbation of renal failure) have been described. In case of overdose, allopurinol significantly inhibits the activity of xanthine oxidase, but only in the case of simultaneous use with 6-mercaptopurine and azathioprine is the drug accompanied by significant side effects.

If an overdose is suspected, especially when 6-mercaptopurine and azathioprine are taken simultaneously, you can wash the stomach, induce vomiting, or take activated charcoal and sodium phosphate, if no more than 1 hour has passed after taking the drug.

Treatment. Symptomatic therapy. If necessary, hemodialysis. Specific antidote is unknown.

Adverse reactions

Reactive gout attacks may occur at the beginning of treatment with allopurinol.

Adverse reactions are most common in the presence of renal and/or hepatic insufficiency or when used concomitantly with ampicillin or amoxicillin.

Skin: Stevens-Johnson syndrome, toxic epidermal necrolysis, alopecia, furunculosis, angioedema, hair discoloration.

The most common skin reactions (approximately 4%) occur at any time during treatment and may present as purpuric, maculopapular, squamous or exfoliative rashes.

On the part of the immune system: delayed-type hypersensitivity reactions accompanied by fever, skin rashes, vasculitis, lymphadenopathy, pseudolymphoma, arthralgia, leukopenia, eosinophilia, hepatosplenomegaly, abnormal liver function tests (reversible increase in transaminases and alkaline phosphatase); acute cholangitis and xanthine stones; anaphylactic shock.

Hepatic: liver dysfunction ranging from asymptomatic elevation of liver function tests to hepatitis (including hepatic necrosis and granulomatous hepatitis).

From the digestive tract: nausea, vomiting, diarrhea; hematemesis, steatorrhea, stomatitis.

On the part of the circulatory system: severe bone marrow damage (thrombocytopenia, agranulocytosis, aplastic anemia), especially in patients with renal failure; changes in blood parameters (leukopenia, leukocytosis, granulocytosis and eosinophilia), pure red cell aplasia.

Respiratory, thoracic and mediastinal disorders: angina pectoris.

Nervous system: ataxia, peripheral neuritis, taste disturbance, coma, headache, neuropathy, paralysis, dizziness, drowsiness, paresthesia.

Cardiovascular system: bradycardia, arterial hypertension.

Metabolic disorders: diabetes mellitus, hyperlipidemia.

Psychiatric: depression.

From the reproductive system: gynecomastia, impotence, infertility.

From the urinary system: hematuria, uremia.

From the organs of vision: cataract, retinal degeneration, visual impairment.

Musculoskeletal system: muscle pain.

General disorders: malaise, asthenia, edema.

Expiration date

5 years.

Storage conditions

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging

300 mg tablets: 10 tablets in a blister; 3 blisters in a pack.

Vacation category

According to the recipe.

Producer

JSC "KYIV VITAMIN FACTORY".

Location of the manufacturer and its business address

04073, Ukraine, Kyiv, Kopylivska St., 38.