Metformin - instructions for use, dose, side effects, contraindications

Excipients: Povidone K-30 - 34.00 mg; macrogol 6000 - 8.30 mg; sorbitol-17.40 mg; magnesium stearate - 8.30 mg). Shell: Opadrai Y-1-7000: hypromellose-10,80 mg; macrogol 400 - 1.30 mg: gitanium dioxide-5.90 mg; paraffin solid-q.s (<l, 6 mg).

Description:

Dosage 500 mg:

from white to white with a yellowish shade of color, round, biconvex tablets, covered with a film sheath, with a risk on one side. On the fracture, the core is white to light yellow in color.

Dosage of 850 mg:

from white to white with a yellowish shade of color, round, biconvex tablets, covered with a film sheath, with a risk on one side. On the fracture, the core is white to light yellow in color.

Pharmacotherapeutic group:The hypoglycemic agent of the biguanide group for oral administration

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin reduces hyperglycemia, without leading to the development of hypoglycemia. Unlike derivatives of sulfonylureas, it does not stimulate insulin secretion and does not have a hypoglycemic effect in healthy individuals. Increases the sensitivity of peripheral receptors to insulin and the utilization of glucose by cells. It inhibits gluconeogenesis in the liver. Delays the absorption of carbohydrates in the intestine. Metformin stimulates the synthesis of glycogen, affecting glycogen synthase.Increases the transport capacity of all types of membrane glucose transporters.

In addition, it has a beneficial effect on lipid metabolism: it reduces the content of total cholesterol, low-density lipoproteins and triglycerides. On the background of taking metformin, the patient's body weight either remains stable or moderately decreases.

Pharmacokinetics:

After oral administration metformin absorbed from the gastrointestinal tract quite fully.

Absolute bioavailability is 50-60%. The maximum concentration (C_max) (approximately 2 μg / ml or 15 μmol) in plasma is achieved after 2.5 hours. With simultaneous intake of food, the absorption of metformin is reduced and delayed. Metformin quickly distributed into tissues, practically does not bind to plasma proteins. Exposed to a very weak degree of metabolism and excreted by the kidneys. The clearance of metformin in healthy subjects is 400 ml / min (4 times more than the creatinine clearance), which indicates the presence of active canaliculia secretion. The half-life is approximately 6.5 hours. With renal insufficiency, it increases, there is a risk of cumulation of the drug.

Indications:

Diabetes mellitus type 2, especially in patients with obesity, with ineffectiveness of diet and exercise:

- in adults as a monotherapy or in combination with other oral hypoglycemic agents, or with insulin;

- in children from 10 years as a monotherapy or in combination with insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or renal dysfunction (creatinine clearance (CC) less than 60 ml / min);

- acute conditions, taking place with the risk of developing a violation of kidney function: dehydration (with diarrhea, vomiting), severe infectious diseases, shock;

- clinically pronounced manifestations of acute or chronic diseases that can lead to the development of tissue hypoxia (including cardiac or respiratory failure, acute myocardial infarction);

- extensive surgery and trauma, when insulin therapy is indicated (see section "Special instructions");

- liver failure, a violation of liver function;

- chronic alcoholism, acute alcohol poisoning;

- Pregnancy;

- lactic acidosis (including in the anamnesis);

- use less than 48 hours before and within 48 hours after radioisotope or X-ray studies with the introduction of an iodine-containing contrast medium (see section "Interaction with other drugs");

- compliance with a low-calorie diet (less than 1000 kcal / day);

- Children under 10 years old.

Carefully:Use the drug in people over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis; in the period of breastfeeding.

Pregnancy and lactation:

A limited amount of evidence suggests that taking metformin in pregnant women does not increase the risk of congenital malformations in children.

When planning pregnancy, and also in case of pregnancy on the background of taking metformin, the drug should be canceled, and insulin therapy is prescribed.

It is necessary to maintain the level of glucose in the blood plasma at the level closest to the norm in order to reduce the risk of fetal malformations.

Metformin is excreted in breast milk. Side effects in newborns with breastfeeding against metformin were not observed.However, due to the limited amount of data, the use of the drug during breastfeeding is not recommended. The decision to stop breastfeeding should be made in consideration of the benefits of breastfeeding and the potential risk of side effects in the child.

Dosing and Administration:

Tablets should be taken orally, swallowed whole, without chewing, during or immediately after eating, with plenty of water.

Adults: monotherapy and combination therapy in combination with other oral hypoglycemic agents:

The usual initial dose is 500 mg or 850 mg 2-3 times a day after or during meals. A further gradual increase in the dose is possible depending on the concentration of glucose in the blood. The maintenance dose of the drug is usually 1500-2000 mg / day. To reduce side effects from the gastrointestinal tract, the daily dose should be divided into 2-3 doses. The maximum dose is 3000 mg / day, divided into three doses. A slow increase in dosage can help improve gastrointestinal tolerance.In case of planning a transition from taking another hypoglycemic agent: it is necessary to stop taking another medication and start taking the drug Metformin in the dose indicated above.

Combination with insulin:

To achieve better control of blood glucose Metformin and insulin can be used as a combination therapy. The usual initial dose of the drug Metformin 500 mg or 850 mg is one tablet 2-3 times a day, while the dose of insulin is selected based on the concentration of glucose in the blood.

Children and adolescents: in children from 10 years of age, the drug Metformin can be used both in monotherapy and in combination with insulin. The usual initial dose is 500 mg or 850 mg once a day after or during a meal. After 10-15 days, the dose should be adjusted based on the blood glucose concentration. The maximum daily dose is 2000 mg, divided into 2-3 doses.

Older patients: because of the possible reduction in renal function, Metformin dose should be selected under regular monitoring of renal function (to determine the concentration of serum creatinine at least 2-4 times a year).The duration of treatment is determined by the doctor. It is not recommended to interrupt the use of the drug without the indication of the attending physician.

Side effects:

The frequency of side effects of the drug is assessed as follows:

Very Frequent: ≥ 1/10

Frequent: ≥1 / 100, <1/10

Infrequent: ≥1 / 1000, <1/100

Rare: ≥ 1/10 000, <1/1000

Very rare: <1/10 000

Unknown: can not be evaluated with the available data.

Side effect is presented in order of decreasing importance.

Disorders from the metabolism and nutrition: Very rarely: lactic acidosis (see "Special instructions").

With prolonged intake of metformin, a decrease in absorption of vitamin B can be observed. When metal of regional anemia is detected, it is necessary to take into account the possibility of such etiology.

Impaired nervous system: Often: a taste disorder

Disorders from the gastrointestinal tract: Very often: nausea, vomiting, diarrhea, abdominal pain and lack of appetite. Most often they occur during the initial period of treatment and in most cases spontaneously pass. To prevent symptoms, it is recommended to take metformin 2 or 3 times a day during or after a meal. Slow increase in dose may improve gastrointestinal tolerance.

Disturbances from the skin and subcutaneous tissues: Very rarely: skin reactions such as erythema, pruritus, rash.

Disorders from the liver and bile ducts: Very rarely: a violation of liver function and hepatitis; after the withdrawal of metformin, these undesirable phenomena completely disappear.

Published data, postmarketing data, as well as controlled clinical trials in a limited children's population in the age group 10-16 years, show that the side effects of children in nature and severity are similar to those in adult patients.

Overdose:

Symptoms: when metformin was used at a dose of 85 g (42.5 times the maximum daily dose), hypoglycemia was not observed, but lactoacidosis was noted.

A significant overdose of metformin or associated risk factors may lead to the development of lactic acidosis (see "Special instructions").

Treatment: in the case of the appearance of signs of lactic acidosis, the drug should be discontinued immediately, the patient must be hospitalized and, having determined the concentration of lactate, clarify the diagnosis. The most effective measure for excretion from the body of lactate and metformin is hemodialysis.Conduct also symptomatic treatment.

Interaction:

Contraindicated combinations

Iodine-containing radiopaque agents: on the background of functional renal insufficiency in patients with diabetes mellitus, a radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis. Treatment with metformin should be canceled depending on the function of the kidneys 48 hours before or during the X-ray examination using iodine-containing radiopaque means and not to resume earlier 48 hours after, provided that during the examination the renal function was found to be normal.

Unrecommended combinations

Alcohol: acute alcohol intoxication increases the risk of lactic acidosis, especially in the following cases:

- malnutrition, compliance with a low-calorie diet;

- Liver insufficiency.

When taking the drug, avoid drinking alcohol and medications containing ethanol. Combinations that require caution

Danazol: It is not recommended simultaneous reception of danazolum in order to avoid hyperglycemic action of the latter.If it is necessary to treat danazol and after stopping the latter, a dose adjustment of metformin is required under the control of the glucose concentration in the blood.

Chlorpromazine: when taken in high doses (100 mg per day) increases the concentration of glucose in the blood, reducing the release of insulin. When treating with neuroleptics and after stopping the intake of the latter, correction of the dose of the drug under the control of the concentration of glucose in the blood is required.

Glucocorticosteroids (GCS) systemic and local effects reduce glucose tolerance, increase the concentration of glucose in the blood, sometimes causing ketosis. In the treatment of GCS, and after discontinuation of the latter, correction of the dose of metformin is required under the control of the concentration of glucose in the blood.

Diuretics: simultaneous administration of "loop" diuretics can lead to the development of lactic acidosis due to possible functional renal failure. Do not assign metformin, if the SC is below 60 ml / min.

Assigned in the form of injections beta₂-adrenomimetics: increase the concentration of glucose in the blood due to stimulation of beta₂adrenoreceptors. In this case, it is necessary to monitor the concentration of glucose in the blood.If necessary, the appointment of insulin is recommended. With the simultaneous use of the above medicines, more frequent monitoring of the glucose level in the blood may be required, especially at the beginning of the treatment. If necessary, the dose of metformin can be adjusted during treatment and after its termination.

Angiotensin converting enzyme inhibitors and other antihypertensive drugs can reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose, salicylates may develop hypoglycemia.

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

Special instructions:

Lactic acidosis

Lactic acidosis is a rare, but serious (high mortality in the absence of emergency treatment) complication, which can occur due to the cumulation of metformin.The cases of lactic acidosis with the use of metformin occurred, mainly, in patients with diabetes mellitus with severe renal failure.

Other associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia, can help to reduce the incidence of lactic acidosis.

The risk of developing lactic acidosis when nonspecific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain, and metformin does not affect growth and puberty. However, in view of the lack of long-term data, careful monitoring of the subsequent influence of metformin on these parameters in children, especially during puberty, is recommended. The most careful control is needed in children aged 10-12 years.

Other Precautions:

Patients are encouraged to continue to follow a diet with an even intake of carbohydrates throughout the day. Patients with excessive body weight are encouraged to continue to follow a low-calorie diet (but not less than 1000 kcal / day).

It is recommended that regular laboratory tests be performed on a regular basis to control diabetes mellitus. Metformin when monotherapy does not cause hypoglycemia, but caution should be exercised when used in combination with insulin or other hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide).

Effect on the ability to drive transp. cf. and fur:

Monotherapy with the drug Metformin does not cause hypoglycemia, therefore does not affect the ability to drive vehicles and mechanisms.

Nevertheless, patients should be cautioned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, repaglinide, insulin), which impairs the ability to drive vehicles and engage in other potentially dangerous activities requiring increased attention and rapid psychomotor reactions.

Form release / dosage:Tablets, film-coated, 500 mg, 850 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film and aluminum foil.By 3 or 6 contour squares, together with the instructions for use, are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Keep in original packaging.

Shelf life:3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000779/08

Date of registration:15.02.2008 / 20.12.2017

Expiration Date:Unlimited

The owner of the registration certificate:Pharmacist, Open CompanyPharmacist, Open Company Russia

Manufacturer: & nbsp

Pharmacist, Open Company Russia

Information update date: & nbsp11.05.2018

Illustrated instructions

Instructions

Metformin (Metformin)