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

Metformin - biguanide with hypoglycemic action, which reduces both basal and postprandial concentration of glucose in the blood plasma, lie stimulates the secretion of insulin and in connection with this nc causes hypoglycemia. 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. On the background of taking metformin, the patient's body weight either remains stable or moderately decreases. Metformin has a beneficial effect on lipid metabolism: reduces the concentration of total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

After oral administration of the drug in the form of a sustained release tablet, the absorption of metformin is slowed compared to the tablet with the usual release of metformin. Time to reach the maximum concentration in the blood plasma (TC_m_Oh) after a single oral administration 1 tablets with prolonged release at a dose of 1000 mg is 5-7 hours (in the range of 4 to 12 hours). At the same time, the TS_m_Oh for a tablet with a conventional release is 2.5 hours.

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration (C_m_Oh) and the area under the curve "concentration-time" (AUC) increase in a disproportionate dose. After a single oral dose of 2000 mg of metformin in the form of sustained-release tablets AUC is similar to that observed after taking 1000 mg of metformin in the form of tablets with the usual release twice a day. The intra-individual variability of C_m_Oh and AUC after taking metformin in the form of tablets with prolonged release is similar to that observed after taking metformin in the form of tablets with normal release.

The absorption of metformin from the sustained-release tablets does not change with the composition of the food taken. No cumulation is observed with repeated administration to 2000 mg of metformin in the form of sustained-release tablets.

Distribution

The connection with plasma proteins is negligible. FROM_m_Oh in the blood below C_m_Oh in plasma and is reached approximately in the same time. Average volume of distribution (V_d) fluctuates in the range of 63-276 liters.

Metabolism

Metabolites in humans are not found.

Excretion

Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is> 400 ml / min, indicating that metformin is excreted due to glomerular filtration and tubular secretion. After oral administration, the half-life is about 6.5 hours.

When the renal function is impaired, the clearance of metformin decreases in proportion to the creatinine clearance, the half-life increases, which can lead to an increase in the concentration of metformin in the blood plasma.

Indications:

Diabetes mellitus type 2 in adults, especially in patients with obesity, with ineffective diet and exercise:

- as a monotherapy:

- in combination with other oral hypoglycemic agents or with insulin.

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 chronic or severe diarrhea, repeated attacks of vomiting), severe infectious diseases (eg, respiratory infections, urinary tract infections), 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 introduction of iodine-containing contrast medium (eg, intravenous urography, angiography) (see section "Interaction with other drugs");

- compliance with hypocaloric diet (less than 1000 kcal / day);

- Children under 18 years of age due to lack of application data.

Carefully:

Apply the drug:

- in patients 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, as well as in the case of pregnancy on the background of taking metformin, the drug should be canceled and prescribed insulin therapy. It is necessary to maintain the concentration of glucose in the blood 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, in connection with limited amount of data 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:

The drug Metformin MB is taken internally.Tablets are swallowed whole, without chewing, squeezed with enough liquid. 1 time per day during dinner. The dose of the drug Metformin MB is selected by the doctor individually for each patient based on the results of measuring the concentration of glucose in the blood.

Monotherapy and combination therapy in combination with other hypoglycemic agents

- For patients who did not take metformin, the recommended initial dose of the drug Metformin MB is 500 mg, 750 mg or 850 mg once a day during dinner.

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

- For patients already receiving metformin treatment, the initial dose of Metformin MB should be equivalent to the daily dose of tablets with conventional release.

- Patients receiving metformin in the form of tablets with the usual release in a dose exceeding 2000 mg, it is not recommended to switch to the drug Metformin MB.

- In the case of planning a transition from another hypoglycemic agent, you must stop taking another remedy.The metformin dose is selected starting with the appointment of the drug Metformin MB 500 mg, 750 mg or 850 mg, with a possible subsequent transition to the drug Metformin MB 1000 mg.

Combination with insulin

To achieve better control of blood glucose concentrations metformin and insulin can be used as a combination therapy. The usual initial dose of Metformin MV is one 500 mg, 750 mg or 850 mg tablet once a day at dinner, while the insulin dose is selected based on the results of measuring blood glucose. Then the transition to the drug Metformin MB 1000 mg is possible.

Daily dose

The maximum recommended dose of the drug Metformin MB:

1) 4 tablets 500 mg per day (2000 mg);

2) 2 tablets 750 mg per day (1500 mg);

3) 2 tablets 850 mg per day (1700 mg);

4) 2 tablets 1000 mg per day (2000 mg).

If adequate glycemic control is not achieved, the dose of Metformin MB can be increased to a maximum daily dose.

To reduce side effects from the gastrointestinal tract, the daily dose of the drug can be divided into 2 divided doses.

If, when taking the maximum recommended dose 1 time per day during dinner, it is not possible to achieve adequate control of the concentration of glucose in the blood,then the maximum dose can be divided into two methods:

- 2 tablets at breakfast time and 2 tablets at dinner for a dosage of 500 mg;

- 1 tablet at breakfast time and 1 tablet at dinner for a dosage of 1000 mg. If adequate control of blood glucose concentration is not achieved by taking the maximum recommended dose of metformin in the form of sustained-release tablets, a transition to metformin in the form of tablets with the usual release with a maximum daily dose of 3000 mg.

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. The initial dose is 500 mg, 750 mg or 850 mg once a day. The maximum dose is 1000 mg per day. Kidney function should be carefully monitored every 3-6 months. If the creatinine clearance is below 45 ml / min, the drug should be discontinued immediately (see "Contraindications").

Elderly patients

Elderly patients are metformin dose adjusted based on renal function assessment, which must be done regularly, at least 2 times per year (see section "Special instructions").

Duration of treatment

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

Dose skip

In case of missed intake of the next dose, the patient should take the next dose at the usual time. Do not take a double dose of Metformin MV.

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.

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 taste disorder (metallic taste in the mouth).

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 during the meal. Slow increase in dose may improve gastrointestinal tolerance.

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.

Disturbances from the skin and subcutaneous tissues: very rarely - skin reactions such as erythema (redness of the skin), itching, hives.

If any of the side effects listed in the manual are aggravated, or any other side effects not indicated in the instructions were noticed, you should notify the doctor.

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 signs of lactic acidosis, the drug should be discontinued, 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 Metformin MV 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 renewed no earlier than 48 hours after, provided that during the examination the kidney function was recognized normal.

Not recommended 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 that require caution

Medicines with indirect hyperglycemic action (eg, glucocorticosteroids (GCS) and tetracosactide (system and local action), beta₂-adrenomimegics, danazol, chlorpromazine when taken in high doses (100 mg per day) and diuretics: more frequent monitoring of blood glucose concentration, especially at the beginning of treatment, may be required. If necessary, the dose of the drug Metformin MB can be adjusted during treatment and after its termination, based on 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.

With the simultaneous use of the drug Metformin MB 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.

Wheezevels when used simultaneously with metformin in the form of tablets e prolonged release increases the concentration of metformin in the blood plasma (increase AUC without a significant increase in C_m_Oh).

Special instructions:

Lactic acidosis

Lactic acidosis is a rare but serious complication (high mortality in the absence of emergency treatment), which can arise from 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.

Lactoacidosis is characterized by severe malaise with general weakness, acidotic dyspnea, vomiting, abdominal pain, muscle cramps 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 lactic 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 start 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 and 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 with simultaneous use of diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

Patients with heart failure have a higher risk of developing hypoxia and renal failure. Patients with chronic heart failure should regularly monitor cardiac function and kidney function during taking metformin. The use of metformin in acute heart failure and chronic heart failure with unstable parameters of hemodynamics is contraindicated.

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 also exercise regularly.

- Patients should inform the physician of any ongoing treatment and any infectious diseases such as a cold, an infection of the respiratory tract or a urinary tract infection.

- It is recommended that regular laboratory tests be performed on a regular basis to control diabetes mellitus.

- Metformin with monotherapy does not cause hypoglycemia,caution should be exercised when used in combination with insulin or other oral hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide, etc.). Symptoms of hypoglycemia are weakness, headache, dizziness, increased sweating, heart palpitations, impaired vision, or impaired concentration.

- It is necessary to warn the patient that inactive components of the drug Metformin MB can be released unchanged through the intestine, which does not affect the therapeutic activity of the drug.

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

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

Nevertheless, the development of hypoglycemia in the use of metformin in combination with other hypoglycemic drugs (derivatives of sulfonylureas, insulin, repaglinide and etc.). When symptoms of hypoglycemia occur, do not drive vehicles and mechanisms.

Form release / dosage:Tablets with sustained release 500 mg, 750 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 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 ns above 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-004302

Date of registration:18.05.2017

Expiration Date:18.05.2022

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

Manufacturer: & nbsp

IZVARINO PHARMA, LLC Russia

Information update date: & nbsp21.06.2017

Illustrated instructions

Instructions

Metformin MB (Metformin MV)