Bagomet Plus^® (Tablets) Instructions for Use

Marketing Authorization Holder

VALEA NT, LLC (Russia)

Manufactured By

Quimica Montpellier, S.A. (Argentina)

ATC Code

A10BD02 (Metformin and sulfonamides)

Active Substances

Metformin (Rec.INN registered by WHO)

Glibenclamide (Rec.INN registered by WHO)

Dosage Forms

	Bagomet Plus®	Film-coated tablets, 2.5 mg+500 mg: 30 pcs.
		Film-coated tablets, 5 mg+500 mg: 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, oblong, biconvex, with an embossed company logo on each side; white in cross-section.

Excipients: croscarmellose sodium, magnesium stearate, starch, microcrystalline cellulose, povidone, lactose monohydrate.

Film coating composition Opadry II white YS-30-18056 (hypromellose, lactose monohydrate, titanium dioxide, triacetin in a ratio of 40:40:10:10), Opadry clear YS-1-7006 (hypromellose, macrogol in a ratio of 90:10), sodium saccharin, vanillin.

10 pcs. – blisters (3) – cardboard packs.

Film-coated tablets blue, oblong, biconvex, with an embossed company logo on each side; white in cross-section.

Excipients: croscarmellose sodium, magnesium stearate, starch, microcrystalline cellulose, povidone, lactose monohydrate.

Film coating composition Opadry II white YS-30-18056 (hypromellose, lactose monohydrate, titanium dioxide, triacetin in a ratio of 40:40:10:10), Opadry clear YS-1-7006 (hypromellose, macrogol in a ratio of 90:10), sodium saccharin, vanillin, brilliant blue.

10 pcs. – blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Oral hypoglycemic drug

Pharmacotherapeutic Group

Oral hypoglycemic agent (second-generation sulfonylurea + biguanide)

Pharmacological Action

A fixed combination of two oral hypoglycemic agents from different pharmacological groups: metformin and glibenclamide.

Metformin belongs to the biguanide group and reduces serum glucose levels by increasing the sensitivity of peripheral tissues to insulin and enhancing glucose uptake. Metformin reduces carbohydrate absorption in the gastrointestinal tract and inhibits gluconeogenesis in the liver. The drug also has a beneficial effect on the lipid profile, reducing levels of total cholesterol, LDL, and triglycerides.

Glibenclamide belongs to the group of second-generation sulfonylurea derivatives. Glucose levels decrease when taking glibenclamide as a result of stimulation of insulin secretion by pancreatic beta cells.

Pharmacokinetics

Metformin is absorbed from the gastrointestinal tract quite completely after oral administration. The absolute bioavailability is from 50% to 60%. When taken simultaneously with food, the absorption of metformin is reduced and delayed.

Metformin is rapidly distributed into tissues and practically does not bind to plasma proteins. It is metabolized to a very small extent and excreted by the kidneys. T_1/2 is approximately 6.5 hours.

Glibenclamide: when taken orally, absorption from the gastrointestinal tract is 48-84%. Time to reach C_max is 1-2 hours, V_d is 9-10 L. Plasma protein binding is 95%. It is almost completely metabolized in the liver to form two inactive metabolites, one of which is excreted by the kidneys and the other with bile. The T_1/2 value ranges from 3 to 10-16 hours.

Indications

Type 2 diabetes mellitus in adults:

• As a second-line drug when diet therapy, physical exercise, and prior therapy with metformin or glibenclamide are ineffective;
• To replace prior therapy with two drugs (metformin and glibenclamide) in patients with stable and well-controlled glycemic levels.

ICD codes

Dosage Regimen

The drug is taken orally. The dose of the drug is determined by the doctor individually for each patient depending on the blood glucose level.

The usual initial dose is 1 tablet of Bagomet Plus 500 mg/2.5 mg or 500 mg/5.0 mg once a day. If necessary, the dose of the drug is adjusted every 1-2 weeks after the start of treatment depending on the blood glucose level.

When replacing prior combination therapy with metformin and glibenclamide, 1-2 tablets of Bagomet Plus 500 mg/2.5 mg or 500 mg/5 mg (depending on the previous dose) are prescribed twice a day – in the morning and in the evening.

The maximum daily dose is 4 tablets of the drug (500 mg/2.5 mg or 500 mg/5 mg, which is 2 g of metformin/20 mg of glibenclamide).

The tablets should be taken with meals.

Adverse Reactions

Due to metformin

• Nausea, vomiting, abdominal pain, loss of appetite are common symptoms at the beginning of treatment and in most cases resolve on their own and do not require special treatment. To prevent the development of these symptoms, it is recommended to take the drug in 2 doses; a slow increase in the dose of the drug also improves its tolerability;
• Metallic taste in the mouth;
• Erythema;
• Megaloblastic anemia;
• Lactic acidosis.

Due to glibenclamide

• Hypoglycemia, hypoglycemic coma (in case of dosage regimen violation and inadequate diet);
• Nausea, vomiting, epigastric pain;
• Increased activity of “liver” enzymes, cholestatic jaundice;
• Leukopenia, thrombocytopenia, rarely – agranulocytosis, hemolytic anemia, pancytopenia;
• “Antabuse effect” when taking alcohol.

Contraindications

• Type 1 diabetes mellitus;
• Diabetic ketoacidosis, diabetic precoma, diabetic coma;
• Hypoglycemia;
• Renal failure or impaired renal function (creatinine level above 135 mmol/L for men and above 110 mmol/L for women);
• Acute conditions that may lead to changes in renal function: dehydration, severe infection, shock, simultaneous intravascular administration of iodine-containing contrast agents;
• Acute or chronic diseases accompanied by tissue hypoxia: cardiac or respiratory failure, recent myocardial infarction, shock;
• Hepatic failure;
• Porphyria;
• Pregnancy, breastfeeding period;
• Simultaneous use of miconazole;
• Infectious diseases, major surgical interventions, trauma, extensive burns and other conditions requiring insulin therapy;
• Chronic alcoholism, acute alcohol intoxication;
• Lactic acidosis (including in history);
• Use for at least 48 hours before and within 48 hours after radioisotope or X-ray examinations with the administration of an iodine-containing contrast agent;
• Adherence to a hypocaloric diet (less than 1000 cal/day);
• Hypersensitivity to the components of the drug, other sulfonylurea derivatives, as well as to excipients.
• It is not recommended to use the drug in persons over 60 years of age performing heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.

Bagomet Plus^® should be used with caution in

• Febrile syndrome;
• Thyroid diseases (with impaired function);
• Hypofunction of the anterior pituitary gland or adrenal cortex.

Use in Pregnancy and Lactation

During treatment with Bagomet Plus^®, it is necessary to inform the doctor about a planned pregnancy and the onset of pregnancy. When planning a pregnancy, as well as in case of pregnancy during the use of Bagomet Plus^®, the drug should be discontinued and insulin therapy prescribed.

Bagomet Plus^® is contraindicated during breastfeeding, as there are no data on its ability to pass into breast milk.

Use in Hepatic Impairment

The drug is contraindicated in hepatic failure.

Use in Renal Impairment

The drug is contraindicated in renal failure or impaired renal function (creatinine level above 135 mmol/L for men and above 110 mmol/L for women).

Contraindicated in acute conditions that may lead to changes in renal function: dehydration, severe infection, shock, simultaneous intravascular administration of iodine-containing contrast agents;

Pediatric Use

Data on the use of Bagomet Plus^® in children are not available.

Geriatric Use

It is not recommended to use the drug in persons over 60 years of age performing heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.

Special Precautions

Special instructions for the patient

During treatment with Bagomet Plus^®, it is necessary to regularly monitor fasting and postprandial blood glucose levels.

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

If vomiting and abdominal pain, accompanied by muscle cramps or general malaise, appear during treatment with Bagomet Plus^®, it is necessary to stop taking the drug and immediately consult a doctor, as these symptoms may be signs of developing lactic acidosis.

It is necessary to inform the doctor about the occurrence of bronchopulmonary infection or urinary tract infection.

48 hours before surgical intervention or intravenous administration of an iodine-containing X-ray contrast agent, Bagomet Plus should be discontinued. Treatment with Bagomet Plus^® is recommended to be resumed after 48 hours.

When taking Bagomet Plus^®, the risk of hypoglycemia is increased in cases of ethanol intake, non-steroidal anti-inflammatory drugs, and fasting. Alcohol consumption is not recommended during treatment.

During treatment with Bagomet Plus, it is not recommended to engage in activities requiring increased attention and speed of psychomotor reactions.

Overdose

Overdose or the presence of risk factors can provoke the development of lactic acidosis, as the drug contains Metformin. Lactic acidosis is a condition requiring emergency medical care; treatment of lactic acidosis should be carried out in a hospital. The most effective method of treatment is hemodialysis.

Overdose can also lead to the development of hypoglycemia due to the presence of glibenclamide in the drug. Symptoms of hypoglycemia: feeling of hunger, increased sweating, weakness, palpitations, pale skin, paresthesia in the oral cavity, tremor, general anxiety, headache, pathological drowsiness, increased fatigue, sleep disorders, feeling of fear, impaired coordination of movements, dizziness, temporary neurological disorders (paresis, sensory disturbances). With the progression of hypoglycemia, loss of self-control and consciousness is possible.

In mild or moderate hypoglycemia, glucose or sugar solution is taken orally. In case of severe hypoglycemia (loss of consciousness), 40% dextrose (glucose) solution or glucagon is administered intravenously, intramuscularly, or subcutaneously. After regaining consciousness, the patient should be given food rich in carbohydrates to prevent recurrent hypoglycemia.

Drug Interactions

The hypoglycemic effect of the drug is enhanced by ACE inhibitors (captopril, enalapril), H2-histamine receptor blockers (cimetidine), antifungal agents (miconazole, fluconazole), non-steroidal anti-inflammatory drugs (phenylbutazone, azapropazone, oxyphenbutazone), fibrates (clofibrate, bezafibrate), antituberculosis drugs (ethionamide), salicylates, coumarin anticoagulants, anabolic steroids, β-blockers, MAO inhibitors, long-acting sulfonamides, cyclophosphamide, biguanides, chloramphenicol, fenfluramine, acarbose, fluoxetine, guanethidine, pentoxifylline, tetracycline, theophylline, tubular secretion blockers, reserpine, bromocriptine, disopyramide, pyridoxine, insulin, allopurinol.

The effect is reduced by barbiturates, glucocorticosteroids, adrenergic agonists (epinephrine, clonidine), antiepileptic drugs (phenytoin), calcium channel blockers, carbonic anhydrase inhibitors (acetazolamide), thiazide diuretics, chlorthalidone, furosemide, triamterene, asparaginase, baclofen, danazol, diazoxide, isoniazid, morphine, ritodrine, salbutamol, terbutaline, glucagon, rifampicin, thyroid hormones, lithium salts, in high doses – nicotinic acid, chlorpromazine, oral contraceptives and estrogens.

Urine-acidifying drugs (ammonium chloride, calcium chloride, ascorbic acid in large doses) enhance the effect by reducing the degree of dissociation and increasing the reabsorption of glibenclamide.

Ethanol increases the likelihood of developing lactic acidosis.

Furosemide increases the C_max of metformin in the blood by 22%.

Nifedipine increases the absorption and C_max, slows down the excretion of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene and vancomycin), secreted in the tubules, compete for tubular transport systems and, with long-term therapy, can increase the C_max of metformin by 60%.

Metformin reduces the C_max and T_1/2 of furosemide by 31% and 42.3%, respectively.

Storage Conditions

Storage conditions

Store in a dry place protected from light at a temperature not exceeding 25°C (77°F).

Keep out of reach of children!

Shelf Life

Shelf life

2 years. Do not use after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

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.