Tablets, film coated 1 tab. metformin hydrochloride 1000 mg.
Oral hypoglycemic agent from the group of biguanides (dimethylbiguanide). The mechanism of action of metformin is associated with its ability to inhibit gluconeogenesis, as well as the formation of free fatty acids and fat oxidation. Increases the sensitivity of peripheral receptors to insulin and glucose utilization 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 and increasing the ratio of insulin to proinsulin. Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters. Delays the absorption of glucose in the intestines. Reduces triglycerides, LDL, VLDL. Metformin improves blood fibrinolytic properties by suppressing a tissue-type plasminogen activator inhibitor. While taking metformin, the patient's body weight either remains stable or decreases moderately.
After oral administration, metformin is slowly and incompletely absorbed from the gastrointestinal tract. Cmax in plasma is reached in approximately 2.5 hours. With a single dose of 500 mg, the absolute bioavailability is 50-60%. With simultaneous ingestion, the absorption of metformin is reduced and delayed. Metformin is rapidly distributed in body tissues. Practically does not bind to plasma proteins. Accumulates in the salivary glands, liver and kidneys. Excreted by the kidneys in unchanged form. T1 / 2 of plasma is 2-6 hours. In case of impaired renal function, cumulation of metformin is possible.
Type 2 diabetes mellitus (non-insulin-dependent) with dietary therapy and exercise failure, in patients with obesity: in adults - as monotherapy or in combination with other oral hypoglycemic agents or insulin in children aged 10 years and older - as monotherapy or in combination with insulin.
Acute or chronic metabolic acidosis, diabetic ketoacidosis, diabetic precoma and co-renal insufficiency, impaired kidney function (CK less than 60 ml / min) dehydration, severe infection, hypoglycemic shock, which can lead to impaired kidney function, clinical signs of acute and chronic diseases that can to the development of tissue hypoxia (includingheart failure, acute myocardial infarction, respiratory failure) use of contrast iodine-containing substances for intravascular administration (including during IV / urography, IV cholangiography, angiography, CT), acute alcohol intoxication, chronic alcoholism and metformin sensitivity.
Use during pregnancy and lactation
Adequate and strictly controlled studies of the safety of metformin in 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 penetrates the placental barrier. Metformin in small quantities is excreted in breast milk, while the concentration of metformin in breast milk can be 1/3 of the concentration in the mother's plasma. Side effects in newborns during breastfeeding while taking metformin were not observed. However, due to the limited amount of data, use during breastfeeding is not recommended. The decision to stop breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the child. In preclinical studies it has been shown that metformin does not have a teratogenic effect in doses that are 2-3 times higher than the therapeutic doses used in humans. Metformin has no mutagenic potential, does not affect fertility.
Dosage and administration
Is ingested, during or after a meal. The dose and frequency of administration depends on the dosage form used. With monotherapy, the initial single dose for adults is 500 mg, depending on the dosage form used, the multiplicity of intake is 1-3 times / day. Perhaps the use of 850 mg 1-2 times / day. If necessary, gradually increase the dose with an interval of 1 week. up to 2-3 g / day. With monotherapy for children aged 10 years and older, the initial dose is 500 mg or 850 1 time / day or 500 mg 2 times / day. If necessary, with an interval of at least 1 week., The dose can be increased to a maximum of 2 g / day in 2-3 doses. After 10-15 days, the dose must be adjusted based on the results of the determination of glucose in the blood.In combination therapy with insulin, the initial dose of metformin is 500-850 mg 2-3 times / day. The insulin dose is selected based on the results of the determination of glucose in the blood.
On the part of the digestive system: possible (usually at the beginning of treatment) nausea, vomiting, diarrhea, flatulence, feeling of discomfort in the abdomen; in rare cases - violation of liver function indicators, hepatitis (disappear after cessation of treatment). Metabolism: very rarely - lactate acidosis (discontinuation of treatment is required). On the part of the blood system: very rarely - a violation of the absorption of vitamin B12. The profile of adverse reactions in children aged 10 years and older is the same as in adults.
Interaction with other drugs
With simultaneous use with sulfonylurea derivatives, acarbose, insulin, salicylates, MAO inhibitors, oxytetracycline, ACE inhibitors, clofibrate, cyclophosphamide, the hypoglycemic effect of metformin may be enhanced. With simultaneous use with corticosteroids, hormonal contraceptives for oral administration, danazol, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, thiazide diuretics, nicotinic acid derivatives may reduce the hypoglycemic effect of metformin. In patients receiving metformin, the use of iodine-containing contrast agents for the purpose of conducting diagnostic studies (including in / in urography, in / in cholangiography, angiography, CT) increases the risk of developing acute renal impairment and lactate acidosis. These combinations are contraindicated. Beta2-adrenomimetiki in the form of injections increase the concentration of glucose in the blood due to the stimulation of 2-adrenergic receptors. In this case, it is necessary to control the concentration of glucose in the blood. If necessary, it is recommended to appoint insulin. Simultaneous use of cimetidine may increase the risk of lactic acidosis. Simultaneous use of "loop" diuretics can lead to the development of lactic acidosis due to possible functional renal failure. Pro concomitant use with ethanol increases the risk of lactic acidosis. Nifedipine increases the absorption and Cmax of metformin. Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin), secreted in the renal tubules, compete with metformin for tubular transport systems and can lead to an increase in its Cmax.
Not recommended for use in acute infections, exacerbations of chronic inflammatory diseases, injuries, acute surgical diseases, the risk of dehydration. Do not use before surgery and for 2 days after their implementation. Caution should be used metformin in elderly patients and those performing heavy physical work, which is associated with an increased risk of developing lactic acidosis. Elderly patients often have asymptomatic renal dysfunction. Special care is required if the renal dysfunction is triggered by taking antihypertensive drugs or diuretics, as well as NSAIDs. If during treatment the patient has muscle cramps, indigestion (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; determination of lactate in plasma should be carried out at least 2 times a year, as well as the appearance of myalgia. When using metformin as monotherapy in accordance with the dosing regimen, hypoglycemia does not usually occur. However, when combined with insulin or sulfonylurea derivatives, there is a risk of hypoglycemia. In such cases, it is necessary to carefully monitor the concentration of glucose in the blood. During treatment, patients should avoid alcohol because of the risk of lactic acidosis. Preclinical studies have shown that metformin does not have carcinogenic potential.