Glibomet film-coated tablets blister pack No. 40

Instructions for use Glibomet film-coated tablets, blister pack No. 40

Composition

active ingredients: metformin hydrochloride and glibenclamide;

1 film-coated tablet contains metformin hydrochloride 400 mg and glibenclamide 2.5 mg;

excipients: colloidal anhydrous silica, macrogol 6000, povidone, croscarmellose sodium, microcrystalline cellulose, glycerol dibehenate, magnesium stearate; Opadry White coating (hypromellose, titanium dioxide (E 171), talc, macrogol 6000).

Dosage form

Film-coated tablets.

Main physicochemical properties: white to off-white, round, biconvex, film-coated tablets, scored on one side and debossed with “2.5” on the flat side and debossed with “B” and “1” on the semicircular halves of the other side.

Pharmacotherapeutic group

Antidiabetic agents. Combination of oral hypoglycemic agents. ATX code A10B D02.

Pharmacological properties

Pharmacodynamics

The drug Glibomet® contains glibenclamide, a second-generation sulfonylurea, which in low doses affects the kinetics of insulin production for a short period of time and repeatedly after each dose, and metformin, a biguanide, which stimulates peripheral tissue sensitivity to insulin action (increasing insulin binding to receptors, enhancing the effect at the postreceptor level), regulates glucose absorption in the intestine, inhibits gluconeogenesis and restores lipid metabolism, reduces excess body weight in overweight diabetic patients, and also reduces platelet adhesion and has a fibrinolytic effect; all these effects are associated with improved tolerability, ease of use and a reduced risk of lactacidemia compared to other biguanides.

The mutually reinforcing activity of the two active components of the drug: the stimulating effect of sulfonylurea on the production of endogenous insulin (pancreatic action) and the direct effect of biguanide on muscle tissue, which leads to a significant increase in glucose absorption (extrapancreatic action), and liver tissue (reduction in gluconeogenesis), allows, at a certain dose ratio, to reduce the content of each component, which contributes to the prevention of excessive stimulation of pancreatic beta cells, and, consequently, to reduce the risk of organ dysfunction, and also ensures safety and a decrease in the frequency of side effects.

Pharmacokinetics

Glibenclamide is 84% absorbed in the digestive tract and excreted through the digestive tract and in the urine after its conversion in the liver into inactive metabolites; the half-life is 5 hours; the degree of binding to plasma proteins is 97%.

Metformin is absorbed in the digestive tract; rapidly excreted in feces and urine; does not bind to plasma proteins, is not metabolized in the body; the half-life in plasma is about two hours.

Indication

Type II diabetes mellitus (non-insulin-dependent diabetes mellitus – NIDDM) with insufficient effectiveness of diet therapy or diet therapy with the use of sulfonylurea drugs or biguanides.

Contraindication

Hypersensitivity to the active substances (glibenclamide, metformin), to other components of the drug or to other sulfonylurea drugs, to sulfonamides; complete ineffectiveness of glibenclamide treatment in type II diabetes mellitus; gestational diabetes mellitus; type I diabetes mellitus (insulin-dependent); any type of acute metabolic acidosis (e.g., lactic acidosis, diabetic ketoacidosis); diabetic coma and precoma; diabetes with episodes of lactic acidosis in history; pancreatectomy; hepatic failure; severe renal failure (glomerular filtration rate (GFR) < 30 ml/min); concomitant therapy with diuretics or antihypertensive drugs that may cause deterioration of renal function, simultaneous intravenous administration of iodinated radiocontrast agents; severe cardiovascular diseases (heart failure class I–IV according to the NYHA (New York Heart Association) classification, cardiogenic or toxic shock, recent myocardial infarction, unstable angina, peripheral arterial circulatory disorders); respiratory failure; adrenocortical insufficiency; acute alcohol intoxication, chronic alcoholism; strict low-calorie diet, especially fasting, and/or malnutrition; acute conditions with a risk of developing renal dysfunction: dehydration, severe infectious diseases; severe degenerative diseases; severe acute bleeding; shock; gangrene; pregnancy and breastfeeding; simultaneous treatment with bosentan; use 2 days before or after surgery; porphyria; concomitant therapy with miconazole (see section "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions

Combinations whose use is contraindicated.

Interactions with glibenclamide.

Miconazole (for systemic use, oral gel) enhances the hypoglycemic effect with possible symptoms of hypoglycemia or even coma (see section "Contraindications").

Combinations that are not recommended for use.

Alcohol – Antabuse effect (alcohol intolerance), especially when using chlorpropamide, glibenclamide, glipizide, tolbutamide.

Increased hypoglycemic action (due to inhibition of compensatory reactions) may lead to hypoglycemic coma.

While taking the drug, you should avoid drinking alcohol and using medications containing alcohol.

Phenylbutazone (for systemic use) enhances the hypoglycemic effect of sulfonylurea derivatives (displaces their binding to plasma proteins and/or reduces their excretion). It is recommended to use another anti-inflammatory drug with fewer interactions, or to warn the patient about the need for increased self-monitoring. If necessary, the dose of the drug should be adjusted during and after therapy with the anti-inflammatory drug.

Antibacterial agents: Concomitant use of sulfonylureas, including glibenclamide, with certain antibacterial agents, such as sulfonamides (e.g. co-trimoxazole), levofloxacin or clarithromycin, may increase the risk of severe hypoglycemia.

Cyclophosphamide: Concomitant use of sulfonylureas, including glibenclamide, and cyclophosphamide may increase the risk of severe hypoglycemia.

Pheniramidol. Concomitant use of sulfonylureas, including glibenclamide, and pheniramidol may increase the risk of severe hypoglycemia.

Interactions with all antidiabetic agents.

Danazol: If this combination is necessary, the patient should be advised to increase blood glucose monitoring. If necessary, the dose of the antidiabetic agent should be adjusted during and after danazol therapy.

Interactions with metformin.

Alcohol: Increased risk of lactic acidosis during acute alcohol intoxication, especially with

starvation, malnutrition; liver failure.

Alcohol consumption and the use of medications containing alcohol should be avoided.

Iodinated radiopaque agents: Metformin should be discontinued prior to or at the time of the radiopaque examination and not resumed until 48 hours afterwards and only after renal function has been re-evaluated and there has been no further deterioration in renal function (see sections 4.2 and 4.4).

Combinations that should be used with caution.

Interactions with all antidiabetic agents.

Chlorpromazine. When taking high doses (100 mg of chlorpromazine per day), blood glucose levels increase (reduced insulin production). The patient should be warned about the need for increased blood glucose control. If necessary, the dose of the hypoglycemic drug should be adjusted during and after therapy with neuroleptics.

Perhexiline. The use of perhexiline may lead to the development of hypoglycemia. When using perhexiline simultaneously with antidiabetic drugs, the patient should be warned about the need for increased control of blood glucose levels.

Corticosteroids (glucocorticoids) and tetracosactides (systemic and local action). Blood glucose levels increase, sometimes accompanied by ketosis (reduced carbohydrate tolerance with corticosteroids, relative insulin deficiency). The patient should be warned about the need for increased blood glucose monitoring. If necessary, the dose of the antidiabetic drug should be adjusted during and after corticosteroid therapy.

β2-agonists. Blood glucose levels increase. The patient should be warned about the need for increased blood glucose control and, if necessary, transferred to insulin therapy.

Angiotensin-converting enzyme inhibitors (e.g. captopril, enalapril). Blood glucose levels decrease. If necessary, the dose of Glibomet® should be adjusted during and after discontinuation of ACE inhibitors.

With metformin.

Organic cation transporter 2 (OCT2)

Caution should be exercised when co-administered with drugs that transport cations and are excreted by the kidneys by tubular secretion (cimetidine or ranolazine). Co-administration of drugs that transport cations affects the pharmacokinetics of metformin hydrochloride, therefore, careful monitoring of blood glucose levels is required. In patients with type 2 diabetes mellitus, co-administration of metformin (1000 mg twice daily) and ranolazine at a dose of 500 mg and 1000 mg twice daily resulted in an increase in metformin plasma exposure by 1.4 and 1.8 times, respectively.

Other interactions.

Some medicinal products may have an adverse effect on renal function, which may increase the risk of lactic acidosis. These include NSAIDs, including selective cyclooxygenase (COX-2) inhibitors, ACE inhibitors, angiotensin II receptor antagonists and diuretics, especially loop diuretics. Careful monitoring of renal function is necessary at the beginning and during treatment with the above-mentioned medicinal products in combination with metformin.

With glibenclamide.

All β-blockers, clonidine, reserpine, guanethidine and sympathomimetics mask symptoms of hypoglycaemia such as palpitations and tachycardia. Most non-selective β-blockers increase the frequency and severity of hypoglycaemic episodes. The patient should be warned and blood glucose monitoring should be increased, especially at the start of therapy.

Fluconazole. Prolongation of the half-life of sulfonylureas with possible symptoms of hypoglycemia. The patient should be warned and blood glucose levels should be monitored more closely. If necessary, the dose of the drug should be adjusted during and after fluconazole therapy.

Bosentan. The risk of hepatotoxicity increases with concomitant administration, therefore these drugs should not be used together. There is a risk of reduced hypoglycemic effect of glibenclamide, as bosentan reduces the concentration of glibenclamide in the blood plasma.

Interactions to consider.

Interactions with glibenclamide.

Desmopressin: Decreased antidiuretic effect.

The hypoglycemic effect of sulfonylureas may be increased by concomitant use with monoamine oxidase inhibitors, chloramphenicol, probenecid, salicylates, sulfinpyrazone; and, conversely, may be reduced by oral contraceptives, thiazide diuretics, and barbiturates.

It should be noted that biguanides may enhance the effect of anticoagulants.

Colesevelam. When used simultaneously, it reduces the concentration of glibenclamide in the blood plasma, which may lead to a decrease in the hypoglycemic effect. This effect was not observed if glibenclamide was taken before the use of other drugs. It is recommended to take Glibomet® at least 4 hours before taking colesevelam.

Application features

Any treatment and, in particular, the transition from one hypoglycemic agent to another is prescribed by a doctor. The patient must strictly follow the doctor's recommendations regarding the dosage and method of administration of the drug, as well as the accompanying diet and exercise regimen. It is recommended to periodically conduct routine diagnostic tests (fasting and postprandial glycemia, HbA1c)

Since glibenclamide is a sulfonylurea derivative, Glibomet® should only be used in patients with type 2 diabetes mellitus when diet therapy is not effective enough.

If symptoms of hypoglycemia appear (see section "Adverse reactions"), saccharides (sugar) are taken; in more severe cases, which may lead to loss of consciousness, a slow intravenous infusion of glucose solution is prescribed.

In case of injuries, surgery, infectious diseases and feverish conditions, it is necessary to switch to temporary insulin treatment for precise control of metabolism.

It is necessary to take into account the possible development of a disulfide-like reaction after taking ethyl alcohol.

Treatment should be discontinued 48 hours before angiography or urography and, if necessary, resumed 48 hours after the examination.

Epidemiological studies have shown that glibenclamide has been associated with an increased risk of cardiovascular mortality compared with metformin or gliclazide. The increased risk of cardiovascular mortality was observed, in particular, in patients with ischemic heart disease.

Lactic acidosis is a rare but very serious metabolic disorder, most often occurring in acute renal failure or cardiorespiratory disease, or sepsis. Metformin accumulation occurs in acute renal failure and increases the risk of lactic acidosis.

In case of dehydration (due to severe diarrhea or vomiting, fever or insufficient fluid intake), metformin should be temporarily discontinued and medical advice should be sought. Medicinal products that may cause acute renal failure (such as antihypertensives, diuretics, NSAIDs [nonsteroidal anti-inflammatory drugs]) should be used with caution in patients receiving metformin. Other risk factors for lactic acidosis include alcohol abuse, hepatic insufficiency, inadequately controlled diabetes, ketosis, prolonged fasting and any disorders that cause hypoxia, as well as the use of medicinal products that may cause lactic acidosis (see sections “Contraindications” and “Interaction with other medicinal products and other types of interactions”).

Patients and/or caregivers should be informed of the risk of lactic acidosis. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, muscle cramps, asthenia, and hypothermia, which may progress to coma. If lactic acidosis is suspected, the patient should discontinue metformin and seek immediate medical attention. Diagnostic laboratory findings include low blood pH (< 7.35), elevated plasma lactate (> 5 mmol/L), increased anion gap, and increased lactate/pyruvate ratio.

Lactic acidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia, and may progress to coma. The diagnosis of lactic acidosis should be suspected in the presence of nonspecific symptoms such as severe fatigue and malaise, vomiting, muscle spasms and digestive disorders such as abdominal pain and complete loss of appetite. Diagnostic laboratory parameters are low blood pH, increased plasma lactate levels, more than 5 mmol/l, increased anion gap and increased lactate/pyruvate ratio. If metabolic acidosis is suspected, further use of the drug should be immediately discontinued and the patient urgently hospitalized. The risk of lactic acidosis depends on the accumulation of metformin in the body, which is possible with worsening renal function. Therefore, renal function should be monitored before starting treatment and regularly during therapy. Patients should be provided with comprehensive information regarding the risk of lactic acidosis.

Kidney function

Glomerular filtration rate (GFR) should be determined before starting treatment and regularly during therapy, see section "Method of administration and dosage". Metformin is contraindicated in patients with GFR < 30 ml/min, the drug should be temporarily discontinued in case of the development of diseases that can worsen renal function, see section "Contraindications".

Deterioration of renal function in elderly patients is common and is not accompanied by specific symptoms. Particular caution is required in cases where renal function may deteriorate, for example, after starting antihypertensive or diuretic therapy, as well as after starting therapy with non-steroidal anti-inflammatory drugs (NSAIDs).

Administration of iodinated contrast agents

Intravascular administration of iodinated radiocontrast agents may result in contrast-induced nephropathy, leading to metformin accumulation and an increased risk of lactic acidosis. Metformin should be discontinued prior to such an examination and may not be resumed until 48 hours after the procedure, provided that renal function has been assessed and stable renal function has been confirmed (see sections 4.2 and 4.5).

Surgical interventions

Metformin should be discontinued prior to surgery under general, spinal or epidural anaesthesia. Metformin should not be restarted until 48 hours after surgery or resumption of independent feeding, provided that renal function has been re-evaluated and that renal function is stable.

Hypoglycemia

Given that the drug contains a sulfonylurea derivative, its use is associated with the risk of hypoglycemia. Appropriate dose adjustment after the start of therapy helps prevent the development of hypoglycemia. Therapy is indicated only for patients who adhere to a regular diet (including breakfast). Regular sugar intake is important, since the risk of hypoglycemia increases with too late meal consumption, insufficient or unbalanced intake of sugars. The likelihood of hypoglycemia increases with a low-calorie diet, after intense or prolonged physical exertion, with the consumption of alcoholic beverages or when used in combination with other hypoglycemic agents.

Elderly patients

Age 65 years and older is an identified risk factor for hypoglycemia in patients receiving sulfonylureas. Hypoglycemia may be difficult to diagnose in the elderly. At the beginning of treatment and in the case of maintenance doses of glibenclamide, the dose should be carefully adjusted to reduce the risk of hypoglycemia (see section "Method of administration and dosage").

Diagnostics.

Symptoms of hypoglycemia include: headache, hunger, nausea, vomiting, severe fatigue, sleep disturbances, nervousness, aggression, impaired concentration and reaction, depression, confusion, speech disorders, visual disturbances, tremor, paralysis and paresthesia, dizziness, delirium, convulsions, drowsiness, fainting, shallow breathing and bradycardia. Excessive sweating, fear, tachycardia, hypertension, palpitations, angina pectoris and arrhythmia may occur due to antiregulatory mechanisms caused by hypoglycemia. The latter symptoms may be absent if hypoglycemia develops slowly, in the presence of autonomic neuropathy, as well as in patients taking beta-blockers, clonidine, reserpine, guanethidine and other sympathomimetics.

Treatment of hypoglycemia.

Individual dosage adjustment and appropriate patient education are important factors in reducing the risk of hypoglycemic episodes. If a patient experiences recurrent hypoglycemic episodes, either severe or associated with unpredictable situations, a change in therapy or the use of another antidiabetic agent other than Glibomet® should be considered.

Factors that contribute to the development of hypoglycemia:

simultaneous alcohol consumption, in particular in combination with fasting; refusal to cooperate or (especially in elderly patients) inability of the patient to cooperate; malnutrition, irregular eating, skipping meals, fasting or changing the diet; imbalance between physical activity and sugar intake; renal failure; severe liver failure; overdose of the drug Glibomet®; some endocrine disorders: insufficiency of the thyroid gland, parathyroid gland and adrenal medulla; simultaneous administration with some other drugs.

Liver and kidney failure.

The pharmacokinetic and/or pharmacodynamic characteristics of Glibomet® may be altered in patients with hepatic impairment or severe renal impairment. Hypoglycemia in such patients may be persistent, and appropriate treatment is necessary.

Informing the patient.

The patient and their close relatives should be informed about the risk of hypoglycemia, the symptoms of the disorder, appropriate treatment and factors contributing to its development. The risk of lactic acidosis should be considered and appropriate information should be provided to the patient in the event of non-specific symptoms such as muscle spasms associated with digestive disorders, abdominal pain and severe asthenia, dyspnea accompanied by acidosis, hypothermia and coma.

The patient should be informed about the importance of following a diet, a regular exercise program, and regularly checking glucose levels.

Potential metabolic decompensation

In the event of trauma, surgery, infectious or febrile illness, or other potential causes of diabetic decompensation, temporary use of insulin in place of current therapy should be considered to maintain adequate metabolic control.

Symptoms of hyperglycemia include frequent urination, extreme thirst, and dry skin.

Concomitant use of glibenclamide and other drugs

The simultaneous use of glibenclamide with alcoholic beverages, phenylbutazone or danazol is not recommended (see section "Interaction with other medicinal products and other types of interactions").

Other caveats

All patients should follow a diet that provides a regular supply of sugar throughout the day. Overweight patients should continue to follow a low-calorie diet.

Regular physical activity is as important as taking Glibomet®.

Regular laboratory tests are necessary (blood glucose, HbA1c).

Hemolytic anemia may develop in patients with G6PD (glucose-6-phosphate dehydrogenase) enzyme deficiency when taking sulfonylureas.

Given that glibenclamide belongs to the sulfonylurea class, caution is recommended when using Glibomet® in patients with G6PD deficiency. Treatment of such patients without sulfonylurea should be considered.

Ability to influence reaction speed when driving vehicles or other mechanisms

Patients should be particularly careful when driving or operating machinery due to the risk of developing symptoms of hypoglycemia.

Use during pregnancy or breastfeeding

The drug is contraindicated for use during pregnancy and breastfeeding.

Pregnancy.

There are no preclinical and clinical data on the use of Glibomet® during pregnancy.

Risk associated with diabetes.

Uncontrolled diabetes during pregnancy (gestational or other types of diabetes) increases the risk of congenital anomalies and perinatal mortality. It is necessary to control diabetes at the time of conception to reduce the risk of congenital anomalies.

Risk associated with metformin.

Animal studies have not revealed any teratogenic effects, therefore, in humans, the development of fetal malformations is not expected, since all teratogenic effects of known substances have been observed in animal studies. Clinical studies have not revealed any evidence of fetal malformations associated with metformin.

Risk associated with glibenclamide.

Animal studies have not revealed any teratogenic effects, therefore, in humans, the development of fetal malformations is not expected, since all teratogenic effects of known substances have been observed in animal studies. In clinical practice, there are no relevant data on the basis of which an assessment of teratogenic or fetotoxic effects is formed when using glibenclamide during pregnancy.

Adequate blood glucose control contributes to the normal course of pregnancy in this category of patients. Glibomet® should not be used for the treatment of diabetes during pregnancy.

If the therapeutic diet is insufficient to fully compensate for the metabolism, insulin treatment is necessary, regardless of the type of disease (type I or II diabetes, gestational diabetes).

Regarding gestational diabetes, it is recommended to replace oral antidiabetic drugs with insulin from the moment of planning pregnancy or immediately upon the onset of pregnancy and use of this drug. It is recommended to monitor the blood glucose level in the newborn.

Breastfeeding.

Since there is insufficient data on the penetration of metformin and glibenclamide into human breast milk, and due to the risk of hypoglycemia in the newborn, the drug is contraindicated for use during breastfeeding.

Method of administration and doses

Dosage.

The dose is determined by the doctor for each patient strictly individually and according to the results of laboratory tests (glycemia, HbA1c).

As a rule, the initial dose is 2 tablets per day, which should be taken with meals. If necessary, the dose can be gradually increased until blood glucose control is achieved. Gradually, the dose of Glibomet® can be reduced to the minimum dose sufficient to maintain blood glucose control.

The maximum recommended daily dose of Glibomet® is 6 tablets.

Adults with normal renal function (GFR ≥ 90 mL/min).

Typically, the starting dose is 2 film-coated tablets per day.
The treatment regimen depends on the individual daily dose, for example:
• 1 film-coated tablet per day during breakfast, if the recommended daily dose is 1 tablet;

1–2 film-coated tablets twice a day, morning and evening, if the recommended daily dose is 2–4 tablets; 1–2 film-coated tablets three times a day, morning, afternoon and evening, if the recommended daily dose is 3–6 tablets.

Kidney failure.

Glomerular filtration rate (GFR) should be measured before starting treatment and at least annually after starting treatment with metformin-containing products. In patients at increased risk of further worsening of renal failure and in elderly patients, renal function should be checked more frequently, namely every 3–6 months.

The maximum daily dose is recommended to be divided into 2-3 doses per day. Before starting treatment with Glibomet®, factors that may increase the risk of lactic acidosis should be analyzed (see section "Special instructions") in patients with GFR <60 ml/min.

In the absence of the drug Glibomet®, separate monocomponent drugs should be used instead of a fixed combination of active substances.

For patients with GFR ≥ 60 and ≤ 89 ml/min, the daily dose of Glibomet® should not exceed the maximum, i.e. 6 film-coated tablets.

For patients with GFR ≥ 45 and ≤ 59 ml/min, the maximum daily dose of Glibomet® should not exceed 5 film-coated tablets.

For patients with GFR ≥ 30 and < 44 ml/min, the daily dose of Glibomet® should not exceed 2 film-coated tablets.

Glibomet® is contraindicated in patients with GFR < 30 ml/min.

Elderly patients.

In this group of patients, the dose of Glibomet® depends on the state of renal function (at the beginning of therapy - 1 tablet of Glibomet®); renal function should be checked regularly (see the section "Special instructions for use").

Patients aged 65 years and over: the initial and maintenance doses of Glibomet® should be carefully adjusted to reduce the risk of hypoglycemia. Treatment should be started with the lowest possible dose and gradually increased if necessary (see section "Special instructions").

Method of application.

The tablets should be swallowed whole during meals, without chewing and with sufficient liquid. To prevent hypoglycemia, it is recommended to eat food with sufficient carbohydrate content after taking the drug.

Combination therapy with insulin.

There are no clinical data on the use of this medicinal product with insulin.

Children

The medicine is contraindicated for use in children.

Overdose

In case of lactic acidosis, the patient should be immediately hospitalized and appropriate therapy should be administered. The most effective measure for removing lactate and metformin from the body is hemodialysis.

Since the drug contains a sulfonylurea, in case of overdose, hypoglycemia may develop (see section "Special instructions") and gastrointestinal symptoms.

Plasma clearance of glibenclamide may be prolonged in patients with liver disease.

Due to its close protein binding, glibenclamide is not removed during hemodialysis.

Adverse reactions

The most common adverse reactions at the beginning of treatment are gastrointestinal symptoms such as nausea, vomiting, diarrhea, abdominal pain, and loss of appetite. In most cases, these symptoms subside with continued treatment. With a gradual increase in the dose, the gastrointestinal tolerability of the drug improves.

Short-term visual disturbances may develop at the beginning of treatment due to hypoglycemia.

Life-threatening or even fatal lactic acidosis may occur during metformin therapy, especially in patients with risk factors such as renal insufficiency and cardiogenic shock. In such severe cases, metformin therapy should be discontinued immediately and appropriate measures should be taken.

Increased blood lactic acid levels, increased lactate/pyruvate ratio, decreased blood pH, and hyperazotemia have been reported, with an exclusively adverse outcome.

Alcohol consumption during treatment contributes to the development of lactic acidosis (see section "Special instructions").

Adverse reactions may develop during treatment with Glibomet®. The following classification is used to assess the frequency of adverse reactions:

very often >1/10; often >1/100, <1/10; sometimes >1/1000, <1/100; rarely >1/10000, <1/1000; very rarely <1/10000.

From the blood and lymphatic system.

Rare: leukopenia, thrombocytopenia.

Very rare: agranulocytosis, hemolytic anemia, bone marrow aplasia, pancytopenia, acute hemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.

These reactions are reversible and disappear after discontinuation of treatment.

From the side of metabolism and nutrition.

Sometimes: acute hepatic porphyria, porphyria cutanea.

Rare: hypoglycemia.

Very rare: lactic acidosis, decreased vitamin B12 levels due to reduced absorption. This etiology is recommended to be considered in patients with megaloblastic anemia.

Disulfiram-like reaction after drinking alcohol.

From the organs of vision.

Common: visual disturbances (temporary).

From the nervous system.

Common: headache, taste disturbance.

From the digestive tract.

Very common: nausea, vomiting, diarrhea, abdominal pain, loss of appetite. Most often, these side effects occur at the beginning of treatment and, as a rule, disappear spontaneously. To prevent the occurrence of side effects from the digestive system, it is recommended to slowly increase the dosage and use the drug Glibomet® 2–3 times a day.

On the part of the hepatobiliary system.

Very rare: hepatitis (treatment should be discontinued immediately); abnormal liver function tests.

On the skin and subcutaneous fat.

Cross-hypersensitivity to sulfonamides and their derivatives may develop.

Rare: pruritus, urticaria, maculopapular rash.

Very rare: allergic granulomatous angiitis, erythema multiforme, exfoliative dermatitis, photosensitivity reactions, urticaria, up to the development of shock.

Additional research methods.