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

auxiliary substances of the film shell: coating system Opadry clear, including [hypromellose - 90.9% or 90.9% or 90.9%, macrogol 400 - 4.55% or 4.55% or 4.55%, macrogol 8000 - 4.55% or 4, 55% or 4.55%] 4.0 mg or 6.8 mg or 21.0 mg.

Description:

Tablets white or almost white, film-coated, biconvex, round (500 mg dosage), oval with risk (dosage 850 mg, 1000 mg). On the cross-section the nucleus is from white to almost white.

Pharmacotherapeutic group:Hypoglycemic agent for oral administration of the biguanide group

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. Reduces the production of glucose by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays the absorption of glucose 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. Clinical studies have also shown the effectiveness of metformin for the prevention of diabetes mellitus in patients with prediabetes with additional risk factors for the development of overt diabetes mellitus type 2,whose lifestyle changes did not allow adequate glycemic control.

Pharmacokinetics:

Absorption and distribution

After oral administration metformin absorbed from the gastrointestinal tract quite fully. Absolute bioavailability is 50-60%. The maximum concentration (C_mOh) (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 is rapidly distributed in tissues, practically does not bind to plasma proteins.

Metabolism and excretion

Exposed to a very weak degree of metabolism and excreted to the kidneysand. The clearance of metformin in healthy subjects is 400 ml / min (in 4 times more than the clearance of creatinine (CC)), 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 metformin.

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 with 10 years as a monotherapy or in combination with insulin.

Prevention of type 2 diabetes in patients with prediabetes with additional risk factors for the development of diabetes mellitus 2 type, in whom lifestyle changes did not allow adequate glycemic control.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance of the drug;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or renal dysfunction (CC less than 45 mL / min);

- acute conditions taking place with the risk of developing renal dysfunction: 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 acute heart failure, chronic heart failure with unstable hemodynamics, respiratory failure, acute myocardial infarction);

- extensive surgery and trauma when Pprovided carrying out insulin therapy (see section "Special instructions");

- hepatic failure, impaired liver function;

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactic acidosis (including and in the anamnesis);

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

- compliance with a hypocaloric diet (less 1000 kcal / day).

Carefully:

Use with caution:

- in persons over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis;

- in patients with renal insufficiency (CC 45-59 ml / min);

- in the period of breastfeeding.

Pregnancy and lactation:

Decompensated diabetes mellitus during pregnancy is associated with an increased risk of congenital malformations and perinatal mortality. 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, as well as in case of pregnancy on the background of taking metformin with prediabetes and type 2 diabetes, the drug should be canceled, and in case of diabetes mellitus 2 type 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 penetrates into 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 taken in consideration of the benefits of breastfeeding and the potential risk of side effects in the child.

Dosing and Administration:

Is taken internally.

Adults:

Monotherapy and combination therapy in combination with other oral hypoglycemic agents for type 2 diabetes mellitus:

- The usual initial dose is 500 mg or 850 mg 2-3 times a day after or during meals.

- Every 10-15 days it is recommended to adjust the dose based on the results of measuring the concentration of glucose in the blood plasma. Slow increase in dose helps reduce side effects from the gastrointestinal tract.

- The maintenance dose of the drug is usually 1500-2000 mg per 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 per day, divided into 3 doses.

- Patients receiving metformin in doses of 2000-3000 mg per day, can be transferred to receive the drug Metformin 1000 mg. The maximum recommended dose is 3000 mg per day, divided into 3 doses.

In case of planning a transition from receiving another hypoglycemic means: it is necessary to stop taking other medications and start taking the drug Metformin in the dose indicated above.

Combination with insulin:

To achieve better control of blood glucose metformin and insulin in patients with diabetes mellitus 2 type can be used as a combination therapy. Usually the initial dose of the drug Metformin is 500 mg or 850 mg 2-3 times a day, while the insulin dose is selected based on the concentration of glucose in the blood.

Children and teens: 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.

Monotherapy for pre-diabetes:

The usual dose is 1000-1700 mg per day after or during meals, divided by 2 reception.

It is recommended to carry out regular glycemic control to assess the need for further use of the drug.

Patients with renal insufficiency:

Metformin can be used in patients with moderate renal insufficiency (CK 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis.

- Patients with KK 45-59 ml / min: the initial dose is 500 mg or 850 mg once a day. The maximum dose is 1000 mg per day, divided by 2 reception.

The function of the kidneys should be carefully monitored (every 3-6 months). If the SC is below 45 ml / min, the drug should be discontinued immediately.

Elderly patients: Because of a possible decrease in renal function, the dose of metformin should be selected pecontrol of renal function (determine the concentration creatinine in serum of blood not less than 2-4 times a year).

Duration of treatment: drug Metformin should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.

Side effects:

The incidence of side effects of metformin is distributed as follows: very often: ≥ 1/10, often: ≥ 1/100, <1/10; infrequently ≥ 1/1000, <1/100; rarely: ≥ 1/10 000, <1/1000; very rarely: <1/10 000; frequency is unknown (can not be estimated from available data).

PStrong actions are presented in order of decreasing importance.

Disorders from the metabolism and nutrition:

Very rarely: lactic acidosis (see section "Special instructions").

With prolonged use of metformin, there may be a decrease in vitamin absorption B₁₂. When detecting megaloblastic anemia, it is necessary to consider the possibility of such an etiology of anemia.

Disturbances from the nervous system:

Often: a violation of taste.

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.

Disturbances from the liver and bile ducts:

Very rarely: a violation of liver function and hepatitis. After the withdrawal of metformin, these undesirable phenomena are completely disappear.

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

Overdose:

When metformin was used, a dose of 85 g of hypoglycemia was not observed. However, lactoacidosis was observed in this case. Significant overdose or associated risk factors may lead to the development of lactic acidosis (see section "Special instructions").

Treatment: in the case of signs of lactic acidosis, metformin treatment should be stopped immediately, the patient urgently hospitalized and, after determining 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 failure in patients with diabetes mellitus, a radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis.

Treatment with drug Metformin it is necessary to cancel depending on the function of the kidneys 48 hours prior to 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 kidney function was recognized normal.

Unrecommended combinations

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

- malnutrition, low-calorie dietita;

- hepatic 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 necessary, treatment with danazol and after discontinuation of the latter requires a dose adjustment of the drug Metformin under the control of the concentration of glucose 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, a dose adjustment is required Metformin under the control of the concentration of glucose in the blood.

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 requires a dose adjustment of the drug Metformin 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 use metformin, if the SC is below 60 ml / min.

Beta₂-adrenomimetiki for parenteral administration: increase the blood glucose concentration due to beta stimulation₂adrenoreceptors. 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.

Hypotensive drugs, with the exception of angiotensin converting enzyme inhibitors, can reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of the drug Metformin from derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine increases absorption and C_mOh 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_mOh.

Special instructions:

Lactic acidosis

Lactic acidosis is a rare but serious (high mortality in the absence of emergency treatment) complication, which may occur due to the cumulation of metformin. Cases of lactic acidosis with metformin were developed mainly in patients with diabetes mellitus with severe renal insufficiency.

Other associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia, should be considered. This can help 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 severe asthenia, should be considered.

Lactic acidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia followed by coma.

Diagnostic laboratory indicators are a decrease in blood pH (less than 7.25), a lactate content in the blood plasma above 5 mmol / l, an increased anion gap and a lactate / pyruvate ratio.

If you suspect a metabolic acidosis, stop taking the medication and consult a doctor immediately.

Surgical operations

The use of metformin should be discontinued 48 hours before scheduled surgical operations and can be continued no earlier than 48 hours after, provided that during the examination the renal function was recognized normal.

Kidney function

Because the metformin is excreted by the kidneys, before the beginning of treatment and regularly in the future, it is necessary to determine the QC:

- at least once a year in patients with normal renal function;

- at least 2-4 times a year in elderly patients, as well as in patients with QC at the lower limit of the norm.

In the case of CC less than 45 ml / min, the use of the drug is contraindicated. Care should be taken if there is a possible impairment of kidney function in elderly patients, while using antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

Patients with heart failure have a higher risk of developing hypoxia and kidney failure.

Patients with chronic heart failure should regularly monitor cardiac function and kidney function during taking metformin.

The use of metformin in heart failure with unstable parameters of hemodynamics is contraindicated.

Children and teens

The diagnosis of Type 2 diabetes mellitus should be confirmed before the start of treatment with metformin.

In clinical studies of 1 year, it was shown that 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 for 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 observe a hypocaloric 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 with monotherapy does not cause hypoglycemia, but it is advisable to use caution when used in combination with insulin or other hypoglycemic agents (for example, derivatives of sulfonylurea, repaglinide, etc.).

Application of the drug Metformin recommended for the prevention of diabetes mellitus 2 type individuals with pre-diabetes and additional risk factors for the development of overt diabetes mellitus 2 type, such as:

- age is less 60 years;

- body mass index (BMI) ≥ 35 kg / m²;

- gestational diabetes mellitus in history;

- family history of diabetes mellitus in relatives of the first degree;

- increased concentration of triglycerides;

- reduced concentration of HDL cholesterol;

- arterial hypertension.

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 developing hypoglycemia when using the drug Metformin in combination with other hypoglycemic drugs (derivatives of sulfonylureas, repaglinide, insulin), which worsens the ability to drive vehicles and engage in other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 500 mg, 850 mg and 1000 mg.

Packaging:

Film coated tablets 500 mg:

For 10, 15, 20 tablets in a contour mesh box made of a polyvinylchloride film and aluminum foil. For 3, 5 or 6 contour squares (for 10 tablets) together with the instruction for use are placed in a cardboard box;

For 2 or 4 contour packs (for 15 tablets) together with the instructions for use are placed in a cardboard box;

For 2 or 3 contour packs (for 20 tablets) together with the instructions for use are placed in a cardboard box.

Film coated tablets 850 mg:

For 10, 15, 20 tablets in a contour mesh box made of a polyvinylchloride film and aluminum foil.

For 2, 3, 4 or 6 contourcell packagings (for 10 tablets) together with the instruction for use are placed in a cardboard box;

For 2 or 4 contour packs (for 15 tablets) together with the instructions for use are placed in a cardboard box;

For 2 or 3 contour packs (for 20 tablets) together with the instructions for use are placed in a cardboard box.

Film coated tablets 1000 mg:

For 10, 15 tablets in a contour mesh box made of a polyvinylchloride film and aluminum foil.

For 3, 5 or 6 contour squares (for 10 tablets) together with the instruction for use are placed in a cardboard box;

For 2, 3 or 4 contour cell packs (for 15 tablets) together with the instructions for use are placed in a cardboard box.

For 20 tablets (all dosages) in a jar of light-protective glass, capped with a lid tightened with a sealing element, or in a jar with a control cover of the first opening.

Each bank along with instructions for medical use is placed in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

Do not apply but the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-004046

Date of registration:27.12.2016 / 10.04.2017

Expiration Date:27.12.2021

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Representation: & nbspPROMO-MED LLC PROMO-MED LLC Russia

Information update date: & nbsp11.05.2018

Illustrated instructions

Instructions

Metformin (Metformin)