Glukogamma (Tablets) Instructions for Use

Marketing Authorization Holder

Izvarino Pharma LLC (Russia)

ATC Code

A10BA02 (Metformin)

Active Substance

Metformin (Rec.INN WHO registered)

Dosage Forms

	Glukogamma	Extended-release tablets 500 mg
		Extended-release tablets 750 mg
		Extended-release tablets 850 mg
		Extended-release tablets 1000 mg

Dosage Form, Packaging, and Composition

Extended-release tablets

10 pcs. – blister packs (12) – cardboard packs (120) – By prescription
10 pcs. – blister packs (3) – cardboard packs (30) – By prescription
10 pcs. – blister packs (6) – cardboard packs (60) – By prescription
10 pcs. – blister packs (9) – cardboard packs (90) – By prescription

Extended-release tablets

10 pcs. – blister packs (12) – cardboard packs (120) – By prescription
10 pcs. – blister packs (3) – cardboard packs (30) – By prescription
10 pcs. – blister packs (6) – cardboard packs (60) – By prescription
10 pcs. – blister packs (9) – cardboard packs (90) – By prescription

Extended-release tablets

10 pcs. – blister packs (12) – cardboard packs (120) – By prescription
10 pcs. – blister packs (3) – cardboard packs (30) – By prescription
10 pcs. – blister packs (6) – cardboard packs (60) – By prescription
10 pcs. – blister packs (9) – cardboard packs (90) – By prescription

Extended-release tablets

10 pcs. – blister packs (12) – cardboard packs (120) – By prescription
10 pcs. – blister packs (3) – cardboard packs (30) – By prescription
10 pcs. – blister packs (6) – cardboard packs (60) – By prescription
10 pcs. – blister packs (9) – cardboard packs (90) – By prescription

Clinical-Pharmacological Group

Hypoglycemic drug of the biguanide group for oral administration

Pharmacotherapeutic Group

Drugs for the treatment of diabetes mellitus; hypoglycemic drugs, other than insulins; biguanides

Pharmacological Action

An oral hypoglycemic agent from the biguanide group (dimethylbiguanide). The mechanism of action of metformin is associated with its ability to suppress gluconeogenesis, as well as the formation of free fatty acids and fat oxidation. It increases the sensitivity of peripheral receptors to insulin and the utilization of glucose by cells. Metformin does not affect the amount of insulin in the blood but changes its pharmacodynamics by reducing the ratio of bound insulin to free insulin and increasing the ratio of insulin to proinsulin.

Metformin stimulates glycogen synthesis by acting on glycogen synthase. It increases the transport capacity of all types of membrane glucose transporters. It delays the absorption of glucose in the intestine.

It reduces the level of triglycerides, LDL, VLDL. Metformin improves the fibrinolytic properties of blood by suppressing the tissue plasminogen activator inhibitor.

While taking metformin, the patient’s body weight either remains stable or decreases moderately.

Pharmacokinetics

After oral administration, Metformin is slowly and incompletely absorbed from the gastrointestinal tract. C_max in plasma is reached in approximately 2.5 hours. With a single dose of 500 mg, the absolute bioavailability is 50-60%. When taken simultaneously with food, the absorption of metformin is reduced and delayed.

Metformin is rapidly distributed in body tissues. It is practically not bound to plasma proteins. It accumulates in the salivary glands, liver, and kidneys.

It is excreted by the kidneys unchanged. T_1/2 from plasma is 2-6 hours.

In case of impaired renal function, accumulation of metformin is possible.

Indications

Type 2 diabetes mellitus (non-insulin-dependent) with ineffective diet therapy and physical exercise, in patients with obesity: in adults – as monotherapy or in combination with other oral hypoglycemic agents or with insulin; in children aged 10 years and older – as monotherapy or in combination with insulin.

ICD codes

Dosage Regimen

Take orally, during or immediately after a meal to reduce gastrointestinal adverse effects.

Swallow tablets whole; do not crush, split, or chew.

Initiate therapy with a low dose to minimize intolerance, typically 500 mg or 850 mg once daily.

Increase the dose gradually, based on glycemic control, at intervals of no less than one week.

For the 500 mg strength, a second evening meal dose may be added after one to two weeks.

The maximum recommended daily dose is 2550 mg for the 850 mg strength and 2000 mg for all other strengths.

Administer the total daily dose in divided doses two to three times per day.

For combination therapy with other oral hypoglycemic agents, use the same dosage principles.

When combined with insulin, initiate metformin at a low dose and adjust insulin dose downward to minimize hypoglycemia risk.

For pediatric patients aged 10 years and older, the usual starting dose is 500 mg twice daily.

The maximum pediatric daily dose is 2000 mg.

Adjust dosage based on regular monitoring of blood glucose and glycated hemoglobin (HbA1c) levels.

In elderly patients, do not titrate to the maximum dose; base dosing on renal function assessment.

Withhold dose for 48 hours before and after procedures involving intravascular iodinated contrast media.

Temporarily discontinue therapy during periods of suspected dehydration, severe infection, or shock.

Adverse Reactions

From the digestive system, the following are possible (usually at the beginning of treatment): nausea, vomiting, diarrhea, flatulence, abdominal discomfort; in isolated cases – impaired liver function tests, hepatitis (disappear after discontinuation of treatment).

From the metabolic system, very rarely – lactic acidosis (requires discontinuation of treatment).

From the hematopoietic system, very rarely – impaired absorption of vitamin B₁₂.

The profile of adverse reactions in children aged 10 years and older is the same as in adults.

Contraindications

Acute or chronic metabolic acidosis, diabetic ketoacidosis, diabetic precoma and coma; renal failure, impaired renal function (CrCl<60 ml/min); dehydration, severe infection, hypoglycemic shock, which may lead to impaired renal function; clinically pronounced symptoms of acute and chronic diseases that can lead to the development of tissue hypoxia (including heart failure, acute myocardial infarction, respiratory failure); the use of iodine-containing contrast agents for intravascular administration (including during intravenous urography, intravenous cholangiography, angiography, CT); acute alcohol intoxication, chronic alcoholism; hypersensitivity to metformin.

Use in Pregnancy and Lactation

Adequate and strictly controlled studies on the safety of metformin use during pregnancy have not been conducted. Use during pregnancy is possible in cases of extreme necessity, when the expected benefit of therapy for the mother outweighs the possible risk to the fetus. Metformin crosses the placental barrier.

Metformin is excreted in small amounts in breast milk, and the concentration of metformin in breast milk can be 1/3 of the concentration in the mother’s plasma. No side effects were observed in newborns during breastfeeding while taking metformin. However, due to limited data, use during breastfeeding is not recommended. The decision to discontinue breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the child.

Preclinical studies have shown that Metformin does not have a teratogenic effect at doses that are 2-3 times higher than the therapeutic doses used in humans. Metformin does not have mutagenic potential and does not affect fertility.

Use in Hepatic Impairment

Contraindicated in severe liver dysfunction.

Use in Renal Impairment

Contraindicated in severe renal dysfunction.

Geriatric Use

It is not recommended to use Metformin in patients over 60 years of age, which is associated with an increased risk of developing lactic acidosis.

Special Precautions

Use is not recommended for acute infections, exacerbation of chronic infectious and inflammatory diseases, injuries, acute surgical diseases, or the risk of dehydration.

Do not use before surgical operations and for 2 days after their performance.

Metformin should be used with caution in elderly patients and persons performing heavy physical work, which is associated with an increased risk of developing lactic acidosis. Asymptomatic impairment of renal function is often observed in elderly patients. Special caution is required if renal impairment is provoked by taking antihypertensive drugs or diuretics, as well as NSAIDs.

If during treatment the patient develops muscle cramps, digestive disorders (abdominal pain) and severe asthenia, it should be borne in mind that these symptoms may indicate the onset of lactic acidosis.

During treatment, it is necessary to monitor renal function; the determination of lactate content in plasma should be carried out at least 2 times a year, as well as when myalgia appears.

When using metformin as monotherapy in accordance with the dosage regimen, hypoglycemia, as a rule, does not occur. However, when combined with insulin or sulfonylurea derivatives, there is a risk of developing hypoglycemia. In such cases, particularly careful monitoring of blood glucose concentration is necessary.

During treatment, patients should avoid alcohol consumption due to the risk of developing lactic acidosis.

Drug Interactions

With simultaneous use with sulfonylurea derivatives, acarbose, insulin, salicylates, MAO inhibitors, oxytetracycline, ACE inhibitors, with clofibrate, cyclophosphamide, an enhancement of the hypoglycemic effect of metformin is possible.

With simultaneous use with corticosteroids, oral hormonal contraceptives, danazol, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, thiazide diuretics, nicotinic acid derivatives, a decrease in the hypoglycemic effect of metformin is possible.

In patients receiving Metformin, the use of iodine-containing contrast agents for diagnostic studies (including intravenous urography, intravenous cholangiography, angiography, CT) increases the risk of developing acute renal impairment and lactic acidosis. These combinations are contraindicated.

Beta₂-adrenomimetics in the form of injections increase blood glucose concentration due to stimulation of β₂-adrenergic receptors. In this case, monitoring of blood glucose concentration is necessary. If necessary, insulin administration is recommended.

Simultaneous administration of cimetidine may increase the risk of developing lactic acidosis.

Simultaneous administration of “loop” diuretics may lead to the development of lactic acidosis due to possible functional renal failure.

With simultaneous administration with ethanol, the risk of developing lactic acidosis increases.

Nifedipine increases the absorption and C_max of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin), which are secreted in the renal tubules, compete with metformin for tubular transport systems and can lead to an increase in its C_max.

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.