Glucophage film-coated tablets 850 mg No. 30

Merck Sante

Composition of the medicinal product:

Pharmacological properties

Pharmacodynamics. The drug Glucophage reduces hyperglycemia without causing hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and does not exhibit a hypoglycemic effect in healthy individuals. Glucophage reduces both the initial glucose level and the glucose level after a meal in the blood plasma.
Metformin works in 3 ways:
causes a decrease in glucose synthesis in the liver by inhibiting gluconeogenesis and glycogenolysis;
improves peripheral glucose uptake and utilization in muscles by increasing insulin sensitivity;
delays the absorption of glucose in the intestine.
Metformin stimulates intracellular glycogen synthesis by acting on glycogen synthetase.
Increases the transport capacity of all types of membrane glucose transporters (GLUT).
In clinical trials, patients' body weight remained stable or moderately decreased with metformin. In addition to its effect on glycemia, Glucophage has a beneficial effect on lipid metabolism. When taking Glucophage in therapeutic doses during controlled, medium- and long-term clinical trials, metformin was noted to reduce total cholesterol, LDL-C, and triglycerides.
Pharmacokinetics
Absorption. After oral administration, metformin is almost completely absorbed from the gastrointestinal tract, 20-30% is excreted in the feces. The time to reach max is 2.5 hours. Absolute bioavailability is about 50-60%.
When taken with food, the absorption of metformin is reduced and slowed down.
Distribution. Binding to plasma proteins is negligible. Metformin penetrates into erythrocytes. C max in blood is lower than C max in plasma and is reached after approximately the same time. Erythrocytes are most likely the second distribution chamber. The mean volume of distribution ranges from 63 to 276 liters.
Metabolism: Metformin is excreted unchanged in the urine. No metabolites have been identified in humans.
Elimination. Renal clearance of metformin is >400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. After oral administration, T½ is approximately 6.5 hours. In renal impairment, renal clearance is reduced in proportion to creatinine clearance and therefore T½ is increased, leading to increased metformin plasma levels.

Indication

type II diabetes mellitus (insulin-dependent) with ineffective diet therapy, especially in patients with excess body weight;
as monotherapy or combination therapy in combination with other oral hypoglycemic agents or in combination with insulin for the treatment of adults;
as monotherapy or combination therapy with insulin for the treatment of children over 10 years of age;
reduction of diabetic complications in adult patients with type 2 diabetes mellitus and overweight who used metformin as a first-line drug when diet therapy was ineffective.

Method of application

Monotherapy or combination therapy in combination with other oral hypoglycemic agents
Adults: The usual starting dose is 500 mg or 850 mg (Glucophage, film-coated tablets, 500 mg or 850 mg) 2-3 times daily with or after meals.
After 10-15 days of treatment, the dose should be adjusted according to the results of blood plasma glucose measurements.
Slowly increasing the dose helps reduce gastrointestinal side effects.
The maximum recommended dose is 3000 mg/day, divided into 3 doses.
When treating high doses, Glucophage, film-coated tablets, 1000 mg, are used.
When switching to treatment with Glucophage, it is necessary to stop taking another antidiabetic agent.
Combination therapy with insulin
To achieve better blood glucose control, metformin and insulin can be used as combination therapy. The usual starting dose is 500 mg or 850 mg of Glucophage 2-3 times a day, while the insulin dose is adjusted according to blood glucose measurements.
Monotherapy or combination therapy with insulin
Children. Glucophage is used in children over 10 years of age. Usually the initial dose is 500 mg or 850 mg of Glucophage once a day during or after meals. After 10-15 days of treatment, the dose should be adjusted according to the results of blood glucose determinations.
Slowly increasing the dose helps reduce gastrointestinal side effects.
The maximum recommended dose is 2000 mg/day, divided into 2-3 doses.
Elderly patients may have decreased renal function, therefore the dose of metformin should be selected based on assessment of renal function, which should be performed regularly (see Precautions).

Contraindication:

SIDE EFFECTS:

The frequency of occurrence is classified into the following categories: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1000 and <1/100), rare (≥1/10,000 and <1/1000), very rare (<1/10,000).
From the nervous system
Common: taste disturbance.
Gastrointestinal tract
Very common: nausea, vomiting, diarrhea, abdominal pain, loss of appetite, metallic taste in the mouth, flatulence. Most often, these side effects occur at the beginning of treatment and, as a rule, disappear spontaneously. To prevent side effects from the gastrointestinal tract, it is recommended to slowly increase the dosage and use the drug 2-3 times a day during or after meals.
From the blood system
Isolated cases: megaloblastic anemia.
Skin and subcutaneous tissue disorders
Very rare: skin rash, erythema, pruritus, urticaria.
Metabolism
Very rare: lactic acidosis.
With prolonged use of the drug, the absorption of vitamin B 12 may decrease, which is accompanied by a decrease in its level in the blood plasma. This is noted when metformin is prescribed to patients with megaloblastic anemia.
Hepatobiliary system
Isolated cases: abnormal liver function tests or hepatitis, which completely resolve after metformin discontinuation.

SPECIAL INSTRUCTIONS:

Lactic acidosis is a rare but serious metabolic complication that may occur as a result of metformin hydrochloride accumulation. Cases of lactic acidosis have been reported in patients with diabetes mellitus and severe hepatic insufficiency. Risk factors for lactic acidosis include poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, hepatic insufficiency, or any condition associated with hypoxia.
Lactic acidosis is characterized by muscle cramps, acidotic dyspnea, abdominal pain and hypothermia, and may progress to coma. If lactic acidosis is suspected, the drug should be discontinued and the patient should be hospitalized immediately.
Renal impairment. Since metformin is excreted by the kidneys, plasma creatinine levels should be monitored before and during treatment with Glucophage, especially in patients with impaired renal function and in the elderly. Caution should be exercised in cases where renal function may be impaired, for example, at the beginning of treatment with antihypertensive agents, diuretics and at the beginning of therapy with non-steroidal anti-inflammatory drugs.
Iodinated radiocontrast agents. When conducting radiological examinations using radiocontrast agents, the use of Glucophage should be discontinued 48 hours before the examination and not resumed earlier than 48 hours after the X-ray examination and assessment of renal function.
Surgical interventions. It is necessary to stop using Glucophage 48 hours before elective surgery, which is performed using general, spinal or epidural anesthesia and not resume earlier than 48 hours after surgery and assessment of renal function.
Children. Clinical studies have not revealed any effect of metformin on growth and puberty in children. However, there is no data on the effect of metformin on growth and puberty with long-term use of Glucophage, so the drug should be used with extreme caution in children during puberty, especially at the age of 10-12 years.
Patients should follow a diet and monitor laboratory parameters. When Glucophage is used simultaneously with insulin or sulfonylurea derivatives, the hypoglycemic effect may be enhanced.
Pregnancy and breastfeeding. When planning pregnancy, as well as in the event of pregnancy during treatment with Glucophage, the drug should be canceled and insulin therapy should be prescribed.
There is no data on the penetration of metformin into breast milk, therefore the drug is contraindicated during breastfeeding. If it is necessary to use the drug Glucophage during this period, breastfeeding is discontinued.
Children. The drug Glucophage is used in children over 10 years of age.
Ability to influence the speed of reactions when driving vehicles or working with other mechanisms. Glucophage does not affect the speed of reactions when driving vehicles or working with other mechanisms, since monotherapy with the drug does not cause hypoglycemia.
However, caution should be exercised when using metformin in combination with other hypoglycemic agents (sulfonylurea derivatives, insulin, repaglinide, etc.) due to the risk of hypoglycemia.

Combinations that are not recommended for use
Acute alcohol intoxication increases the risk of lactic acidosis, especially in cases of fasting or low-calorie diet, as well as in liver failure. During treatment with the drug, alcohol consumption and taking medications containing alcohol should be avoided.
Iodine-containing radiopaque agents may cause the development of lactic acidosis in patients with diabetes mellitus on the background of functional renal failure. The use of the drug should be discontinued before radiological examinations and not resumed earlier than 48 hours after radiological examinations using radiopaque agents.
Combinations that should be used with caution
Glucocorticosteroids of systemic and local action, β 2 -sympathomimetics, diuretics have a hyperglycemic effect. It is necessary to constantly monitor the level of glucose in the blood, especially at the beginning of treatment. During and after the termination of such combined therapy, it is necessary to adjust the dose of Glucophage under the control of the level of glycemia.
When used simultaneously with ACE inhibitors, hypoglycemic action may be enhanced. Chlorpromazine, when taken in high doses (100 mg/day), increases glycemia, reducing insulin release. When treated with neuroleptics and after stopping the latter, Glucophage dose adjustment is required under the control of glycemia.

Conditions and shelf life

When using the drug at a dose of 85 g, hypoglycemia was not observed, but in this case lactic acidosis occurred. In the event of lactic acidosis, treatment with the drug should be discontinued, the patient should be urgently hospitalized and, having determined the lactate concentration, the diagnosis should be clarified. The most effective measure for removing lactate and Glucophage from the body is hemodialysis. Symptomatic treatment is also performed.

STORAGE CONDITIONS:

at a temperature not exceeding 25 °C.