Glibenfazh (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmasintez-Tyumen, LLC (Russia)

ATC Code

A10BD02 (Metformin and sulfonamides)

Active Substances

Metformin (Rec.INN registered by WHO)

Glibenclamide (Rec.INN registered by WHO)

Dosage Forms

	Glibenfazh	Film-coated tablets, 2.5 mg + 500 mg: 10, 20, 30, 40, 60, 90, 100 or 120 pcs.
		Film-coated tablets, 5 mg + 500 mg: 10, 20, 30, 40, 60, 90, 100 or 120 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oval, biconvex; the core on the cross-section is white or almost white.

Excipients: hypromellose – 16 mg, croscarmellose sodium – 20.5 mg, sodium stearyl fumarate – 7 mg, povidone K30 – 15 mg, povidone (kollidon F90) – 19 mg.

Film coating composition: hypromellose E15 – 7 mg, macrogol 6000 (polyethylene glycol 6000) – 0.9 mg, titanium dioxide – 2 mg, polysorbate 80 (Tween 80) – 0.1 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.
120 pcs. – jars (1) – cardboard packs.

Film-coated tablets white, capsule-shaped, biconvex; the core on the cross-section is white or almost white.

Excipients: hypromellose – 16 mg, croscarmellose sodium – 18 mg, sodium stearyl fumarate – 7 mg, povidone K30 – 15 mg, povidone (kollidon F90) – 19 mg.

Film coating composition: hypromellose E15 – 7 mg, macrogol 6000 (polyethylene glycol 6000) – 0.9 mg, titanium dioxide – 2 mg, polysorbate 80 (Tween 80) – 0.1 mg.

10 pcs. – contour cell packaging (1) – cardboard packs.
10 pcs. – contour cell packaging (2) – cardboard packs.
10 pcs. – contour cell packaging (3) – cardboard packs.
10 pcs. – contour cell packaging (4) – cardboard packs.
10 pcs. – contour cell packaging (6) – cardboard packs.
10 pcs. – contour cell packaging (9) – cardboard packs.
10 pcs. – contour cell packaging (10) – cardboard packs.
30 pcs. – jars (1) – cardboard packs.
40 pcs. – jars (1) – cardboard packs.
60 pcs. – jars (1) – cardboard packs.
90 pcs. – jars (1) – cardboard packs.
100 pcs. – jars (1) – cardboard packs.
120 pcs. – jars (1) – cardboard packs.

Clinical-Pharmacological Group

Hypoglycemic agent for oral administration (second-generation sulfonylurea derivative + biguanide)

Pharmacotherapeutic Group

Oral hypoglycemic agent (second-generation sulfonylurea + biguanide)

Pharmacological Action

Oral combined hypoglycemic agent, a second-generation sulfonylurea derivative.

It has pancreatic and extrapancreatic effects.

Glibenclamide stimulates insulin secretion by lowering the glucose irritation threshold of pancreatic beta-cells, increases insulin sensitivity and the degree of its binding to target cells, increases insulin release, enhances the effect of insulin on glucose uptake by muscles and liver, and inhibits lipolysis in adipose tissue. It acts in the second phase of insulin secretion.

Metformin inhibits gluconeogenesis in the liver, reduces glucose absorption from the gastrointestinal tract and increases its utilization in tissues; reduces the content of triglycerides and cholesterol in blood serum. It increases insulin binding to receptors (the therapeutic effect does not manifest in the absence of insulin in the blood). It does not cause hypoglycemic reactions.

The hypoglycemic effect develops after 2 hours and lasts for 12 hours.

Pharmacokinetics

Glibenclamide is rapidly and sufficiently completely (84%) absorbed in the gastrointestinal tract, time to reach C_max is 7-8 hours.

Plasma protein binding is 97%.

It is almost completely metabolized in the liver to inactive metabolites.

50% is excreted by the kidneys, 50% with bile. T_1/2 is 10-16 hours.

Metformin, after absorption in the gastrointestinal tract (absorption 48-52%), is excreted by the kidneys (mainly unchanged), partially by the intestines. T_1/2 is 9-12 hours.

Indications

Type 2 diabetes mellitus (in case of ineffectiveness of diet therapy or monotherapy with oral hypoglycemic drugs).

ICD codes

Dosage Regimen

Take orally with meals.

The dosing regimen and duration of treatment are determined by the attending physician depending on the state of carbohydrate metabolism and blood glucose concentration.

The initial daily dose is usually, depending on the dosage form used, from 2.5 mg glibenclamide + 400-500 mg metformin to 7.5 mg glibenclamide + 1.2-1.5 g metformin, with further gradual selection of an effective dose until stable normalization of blood glucose concentration is achieved.

Depending on the dosage of active substances in the dosage form used, the maximum daily dose can be 15 mg glibenclamide + 2.4-3 g metformin or 20 mg glibenclamide + 2 g metformin.

Adverse Reactions

From the digestive system: nausea, vomiting, abdominal pain, decreased appetite, metallic taste in the mouth, decreased absorption and, as a consequence, concentration of cyanocobalamin in blood plasma (with long-term use), discomfort in the epigastric region, increased activity of liver transaminases, hepatitis.

From the skin: erythema (as a manifestation of hypersensitivity), photosensitization, skin itching, maculopapular rash (including on mucous membranes), urticaria.

From metabolism: lactic acidosis, hypoglycemia, cutaneous and hepatic porphyria; hyponatremia, hypercreatininemia, increased urea in blood plasma.

From the hematopoietic system: leukopenia, thrombocytopenia, agranulocytosis, hemolytic anemia, bone marrow aplasia, pancytopenia.

Other: disulfiram-like reactions (with simultaneous use with ethanol).

Contraindications

Hypersensitivity to the components of the combination, type 1 diabetes mellitus; diabetic ketoacidosis; diabetic precoma and coma; lactic acidosis (including in history); renal failure (creatinine clearance <30 ml/min); acute conditions that may lead to impaired renal function (including dehydration, severe infections, shock, intravascular administration of iodine-containing contrast agents); acute and chronic diseases accompanied by tissue hypoxia (including heart failure, respiratory failure, recent myocardial infarction, shock); hepatic failure; acute alcohol intoxication, chronic alcoholism; porphyria; extensive surgical operations and injuries when insulin therapy is required; simultaneous use of miconazole; simultaneous use with bosentan; pregnancy, lactation period; children and adolescents under 18 years of age; use within 48 hours before or 48 hours after radioisotope or X-ray studies with the administration of iodine-containing contrast substance.

With caution

Moderate renal failure; patients aged 60 years and older performing heavy physical work (due to the risk of lactic acidosis); elderly patients over 65 years of age.

Use in Pregnancy and Lactation

Contraindications: pregnancy; lactation period.

Use in Hepatic Impairment

Contraindication – hepatic failure.

Use in Renal Impairment

Contraindication – renal failure (creatinine clearance < 30 ml/min). In patients with moderate renal impairment, dose adjustment is required depending on creatinine clearance.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age.

Geriatric Use

Use with caution in patients aged 60 years and older performing heavy physical work (due to the risk of lactic acidosis); in elderly patients over 65 years of age.

Special Precautions

Major surgical interventions and injuries, extensive burns, infectious diseases with febrile syndrome may require discontinuation of oral hypoglycemic drugs and prescription of insulin.

It is necessary to regularly monitor fasting and postprandial blood glucose levels, and the daily blood glucose curve.

Patients should be warned about the increased risk of hypoglycemia in cases of ethanol intake, NSAIDs, and fasting.

Dose adjustment is necessary during physical and emotional stress, and changes in diet.

Use with caution during therapy with beta-blockers.

In case of hypoglycemia symptoms, carbohydrates (sugar) are used; in severe cases, a dextrose solution is administered intravenously slowly.

This agent must be discontinued 2 days before any angiographic or urographic examination (therapy is resumed 48 hours after the examination).

Against the background of consumption of ethanol-containing substances, disulfiram-like reactions may develop.

Effect on ability to drive vehicles and mechanisms

During treatment, caution must be exercised when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Miconazole – risk of hypoglycemia (up to coma).

Fluconazole – risk of hypoglycemia (increases T_1/2 of sulfonylurea derivatives).

Phenylbutazone can displace sulfonylurea derivatives (Glibenclamide) from protein binding, which can lead to an increase in their plasma concentration and the risk of hypoglycemia.

Use of iodine-containing X-ray contrast agents (for intravascular administration) can lead to the development of impaired renal function and accumulation of metformin, which increases the risk of lactic acidosis. Treatment with the drug is discontinued 48 hours before their administration and resumed no earlier than 48 hours later.

Use of ethanol-containing agents against the background of glibenclamide can lead to the development of disulfiram-like reactions.

Corticosteroids, beta₂-adrenergic agonists, diuretics can lead to a decrease in the effectiveness of the drug; dose adjustment of the drug may be required.

ACE inhibitors – risk of hypoglycemia during the use of sulfonylurea derivatives (Glibenclamide).

Beta-blockers increase the frequency and severity of hypoglycemia.

Antibacterial agents from the sulfonamide group, fluoroquinolones, anticoagulants (coumarin derivatives), MAO inhibitors, chloramphenicol, pentoxifylline, hypolipidemic agents from the fibrate group, disopyramide – risk of hypoglycemia during the use of glibenclamide.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.