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

The composition of the tablet shell: hypromellose - 7.41 mg, titanium dioxide - 5.70 mg, polydextrose - 2.85 mg, talc - 1.90 mg, macrogol 3350-1.14 mg.

1 tablet, film-coated, 850 mg contains:

Tablet core composition:

Active substance: metformin hydrochloride 850.0 mg.

Excipients: Povidone (Kollidone 90 F) - 30.6 mg, giprolase low-substituted - 51.0 mg, glyceryl dibehenate - 83.3 mg, magnesium stearate - 5.1 mg.

The composition of the tablet shell: hypromellose - 12.48 mg, titanium dioxide - 9.60 mg, polydextrose - 4.80 mg, talc - 3.20 mg, macrogol 3350 - 1.92 mg.

1 tablet, film-coated, 1000 mg contains:

Tablet core composition:

Active substance: metformin hydrochloride - 1000.0 mg.

Excipients: Povidone (Kollidone 90 F) - 36.0 mg, giprolase low-substituted - 60.0 mg, glyceryl dibehenate - 98.0 mg, magnesium stearate - 6.0 mg.

The composition of the tablet shell: hypromellose - 14.82 mg, titanium dioxide 11.40 mg, polydextrose - 5.70 mg, talc - 3.80 mg, macrogol 3350 - 2.28 mg.

Description:Tablets are oval in shape, biconvex, covered with a film coat of white or almost white, with a risk on one side and embossed with the symbol "f" another.

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, sulfonylurea 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 due to inhibition of gluconeogenesis and glycogenolysis.

Delays the absorption of glucose in the intestine.

Metformin stimulates the synthesis of glycogen, affecting glycogen synthase. Increases 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_m_Oh) (approximately 2 μg / ml or 15 μmol) in plasma is achieved after 2.5 hours.With simultaneous intake of food, absorption of metformin is reduced and delayed. Metformin quickly distributed into tissues, practically does not bind to plasma proteins.

Metabolism and excretion

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 greater than the creatinine clearance), which indicates the presence of active tubular 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.

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

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or impaired renal function (creatinine clearance 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 insulin therapy is indicated (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 administration of an iodine-containing contrast medium (seesection "Interaction with other drugs");

- adherence to a hypocaloric diet (less than 1000 kcal / day).

Carefully:

Apply the drug:

- 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 (creatinine clearance 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, and also 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 type 2 diabetes, insulin therapy is prescribed. It is necessary to maintain the concentration of glucose in the blood plasma at the level closest to normal, 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 / 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.

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

In the case of planning a transition from taking another hypoglycemic agent, it is necessary to stop taking another medication and begin 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 type 2 diabetes can be used as a combination therapy. The usual 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 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 concentration of glucose in the blood.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 into 2 divided doses.

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 (creatinine clearance 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis.

In patients with a creatinine clearance of 45-59 ml / min, the initial dose is 500 mg or 850 mg once daily. The maximum dose is 1000 mg per day, divided into 2 doses.

The function of the kidneys should be carefully monitored (every 3-6 months).

If the creatinine clearance is below 45 ml / min, the drug should be discontinued immediately.

Older patients: because of the possible decrease in renal function, the dose of metformin should be selected under regular monitoring of renal function (to determine the concentration of serum creatinine at least 2-4 times a year).

Duration of treatment: a 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 frequency of side effects of the drug is assessed as follows:

very often: ≥ 1/10; often: ≥ 1/100, <1/10: infrequent: ≥ 1/1000, <1/100; rarely ≥ 1/10 000, <1/1000; very rarely: <1/10 000. Side effect is presented in descending order significance.

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 absorption of vitamin B12. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

Impaired 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.

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 child 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:

When metformin was used at a dose of 85 g (42.5 times the maximum daily dose), there was no development of hypoglycemia. 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 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 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 should be canceled depending on the function of the kidneys 48 hours before or at the time of the radiographic examination using iodine-containing radiopaque agents and do not resume earlier 48 hours after, provided that during the examination the kidney function was normal.

Unrecommended combinations

Alcohol: acute alcohol intoxication increases the risk of developing lactic acidosis, especially in the case of:

- malnutrition, low-calorie diet;

- hepatic insufficiency.

When taking the drug, avoid drinking alcohol and medications containing ethanol.

Combinations, requiring caution

Danazol: It is not recommended to take danazol concurrently 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 metformin is required under the control of glucose concentration.

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 stopping the intake of the latter, correction of the dose of metformin is required under the control of glucose concentration.

Diuretics: simultaneous administration of "loop" diuretics can lead to the development of lactic acidosis due to possible functional renal failure. Do not prescribe a drug Metformin, if the creatinine clearance is less than 60 ml / min.

Assigned as injections of beta2-adrenomimetics: increase the concentration of glucose in the blood due to stimulation of beta2-adrsporeceptors. 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 blood glucose concentration may be required, especially at the beginning of treatment. If necessary, the dose of metformin can be adjusted during treatment and after its termination.

Hypotensive medicines, with the exception of inhibitors of angiotensin-converting enzyme, 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 possibly the development of hypoglycemia.

Nifedipine increases absorption and C_m_Oh 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_m_Oh.

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 related risk factors, such as uncompensated 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 plasma lactate concentration in excess of 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 planned surgery and can be continued no earlier than 48 hours after,that during the examination renal function was recognized as normal.

Kidney function

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

- 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 creatinine clearance at the lower limit of the norm.

In the case of creatinine clearance less than 45 ml / min, 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, due to 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 should continue to observe a hypocaloric diet (but not less than 1000 kcal / day).

- Patients should inform the doctor about any ongoing treatment and any infectious diseases.

- 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.).

The use of metformin is recommended for the prevention of type 2 diabetes mellitus to persons with prediabetes and additional risk factors for the development of overt diabetes mellitus type 2, such as:

- age is less than 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.

Symptoms of hypoglycemia are weakness, headache, dizziness, increased sweating, heart palpitations, impaired vision, or impaired concentration.

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

Monotherapy with 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 (sulfonylureas, insulin, repaglinide and etc.).

Form release / dosage:

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

Packaging:

For 10 or 15 tablets in a contour mesh box made of PVC film and foil of aluminum printed lacquered or 30 or 60 tablets in a vial or jar, capped with a lid with or without a first opening, of polyethylene.

One bottle or bank, or 3, 6, 9 or 12 contour packs of 10 tablets, or 2, 4, 6 or 8 contiguous cell packs of 15 tablets together with the medical instruction are placed in a pack of cardboard boxes.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004257

Date of registration:25.04.2017

Expiration Date:25.04.2022

The owner of the registration certificate:IZVARINO PHARMA, LLC IZVARINO PHARMA, LLC Russia

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Information update date: & nbsp01.06.2017

Illustrated instructions

Instructions

Metformin (Metformin)