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

Description:Round biconvex tablets covered with a pink film coating (doses of 500 mg and 850 mg) or oval biconvex tablets with deep risk, covered with a pink film coating (dosage 1000 mg). On the cross-section the nucleus is 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 the metabolism of lipids: reduces the concentration 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 It is absorbed from the gastrointestinal tract (GIT) quite full. Absolute bioavailability is 50-60%. The maximum concentration (CmAh) in blood plasma (approximately 2 μg / ml or 15 μmol) 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 blood plasma proteins.

Metabolism

Exposed to a very weak degree of metabolism and excreted by the kidneys. The clearance of metformin in healthy volunteers is 400 ml / min (4 times greater than the creatinine clearance), which indicates the presence of active tubular secretion.

Excretion

The half-life (T1/2) 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 ineffective 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 type 2 diabetes, in whom lifestyle changes did not allow adequate glycemic control.

Contraindications:

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

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or impaired renal function (creatinine clearance less than 45 ml / min);

- acute conditions that occur at a risk of developing renal dysfunction: dehydration (with diarrhea, vomiting), severe infectious diseases, shock;

- clinically pronounced manifestations of acute and / or chronic diseases that can lead to the development of tissue hypoxia (acute heart failure, chronic heart failure with unstable hemodynamics, respiratory failure, acute myocardial infarction);

- extensive surgery and trauma, when insulin therapy is indicated;

- hepatic failure, a violation of liver function:

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactic acidosis (including and in the anamnesis);

- application for at least 48 hours before and within 48 hours after carrying out radioisotope or X-ray studies with the introduction of iodine-containing contrast medium;

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

- lactose intolerance, lactase deficiency and / or glucose-galactose malabsorption.

Carefully:

- In patients over 60 years of age, performing 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 case of pregnancy on the background of taking metformin in pre-diabetes 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 the norm in order to reduce the risk of fetal malformations.

Metformin penetrates into breast milk. Side effects in newborns with breastfeeding while taking metformin drugs were not observed. However, due to the limited amount of data, the use of the drug in the period of breastfeeding ns is 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:

Apply inside, swallowing without chewing, during or immediately after eating, with plenty of water.

Adults:

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

The usual initial dose is 500 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 digestive 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 receptions.

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

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 in patients with type 2 diabetes can be used as a combination therapy. The usual initial dose of metformin is 500 mg or 850 mg 2-3 times a day after or during meals, 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 metformin can be used both in monotherapy and in combination with insulin.The usual initial dose is 500 or 850 mg once a day after or during meals. After 10-15 days the dose should be adjusted for 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 a meal, 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.

Patients with creatinine clearance 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 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.

Elderly patients:

Because of the possible decrease in kidney function, the dose metformin it is necessary to select under regular control indicators of kidney function (determination of the concentration of creatinine in the blood plasma at least 2-4 times a year).

Duration of treatment:

Metformin MC should be taken daily, without interruption. The duration of the drug is determined by the doctor. It is not recommended to interrupt the use of the drug without the consent of the attending physician.

Side effects:

The frequency of adverse reactions is classified according to the recommendations of the World Health Organization: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), the frequency is unknown (the incidence of undesirable reactions can not be estimated from the available data).

Disorders from the metabolism and nutrition:

Very rarely: lactic acidosis (see "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

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. A slow increase in the dose may improve the tolerability of the gastrointestinal tract.

Disorders from the liver and bile ducts:

Very rarely: a violation of liver function and hepatitis; after discontinuation of the drug, these undesirable phenomena completely disappear.

Disturbances from the skin and subcutaneous tissues:

Very rarely: skin reactions - erythema, pruritus, rash.

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

Overdose:

With the use of metformin in a dose of 85 g, the development of hypoglycemia was not observed, but the development of lactic acidosis was observed. Significant overdose or associated risk factors may lead to the development of lactic acidosis (see "Special instructions").

Treatment: in case of signs of lactic acidosis treatment with the drug should be stopped immediately, the patient urgently 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.

Early symptoms of lactic acidosis are nausea, vomiting, diarrhea, fever, abdominal pain, muscle pain, there may be more rapid breathing, dizziness, impaired consciousness and coma development.

Treatment: In case of signs of lactic acidosis, treatment with the drug metformin it is necessary to immediately stop, the patient urgently hospitalized and, having determined the concentration of lactate, to 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: Radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis in patients with diabetes mellitus on the background of functional renal failure.Metformin should be withdrawn, depending on the function of the kidneys, 48 hours before or at the time of the radiographic examination, and not resumed earlier than 48 hours after the radiographic examination using radiopaque means, provided that the kidney function is normal during the examination.

Unrecommended combinations

Alcohol

Alcohol intake increases the risk of lactic acidosis during acute alcohol intoxication, especially in cases of malnutrition or low-calorie diet, as well as liver failure. During therapy, the drug should stop using alcohol and medications containing ethanol.

Combinations, requiring caution

Danazol

It is not recommended simultaneous reception of danazol in order to avoid hyperglycemic action of the latter. When combined, if necessary, therapy with danazol, also after its discontinuation, a dose adjustment of metformin is required controlling the concentration of glucose in the blood plasma.

Chlorpromazine: when taken in high doses (100 mg per day) increases the concentration of glucose in the blood plasma, reducing the release of insulin.In the treatment of neuroleptics 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 plasma.

Combinations that require special care:

Glucocorticosteroids (SCS) of systemic and local action reduce glucose tolerance, increase the concentration of glucose in the blood, sometimes causing ketosis. When performing therapy with GCS and after its termination, it is necessary to correct the dose of metformin under the control of the concentration of glucose in the blood plasma.

Diuretics: simultaneous administration of loop diuretics can lead to the development of lactic acidosis because of the possible functional renal failure. Do not assign metformin, if the creatinine clearance is less than 60 ml / min.

Assigned as injections of beta-2 adrenomimetics: increase the concentration of glucose in blood plasma due to stimulation of beta-2-adrenergic receptors. 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 drugs with the exception of angiotensin converting enzyme inhibitors

Can reduce the concentration of glucose in the blood plasma. If necessary, you need to adjust the dose of metformin.

With the simultaneous use of metformin with derivatives sulfonylureas, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine increases absorption and Cmah of 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 CmOh.

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.

It is necessary to take into account the risk of developing lactic acidosis with the appearance of nonspecific signs, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe asthenia. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia followed by coma.

Diagnostic laboratory indicators are a decrease in blood pH (less 7,25), lactate in the blood plasma above 5 mmol / l, increased anion gap and 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 surgery and can be continued no earlier than 48 hours after, provided that during the examination the renal function was normal.

Kidney function

Because the metformin 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 border norms. In the case of creatinine clearance less than 45 ml / min, the drug is contraindicated.

Special care should be taken in the event of possible impairment of renal function in elderly patients, with simultaneous use of antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.

FROMcardiac insufficiency

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

It is recommended that regular laboratory tests be performed on a regular basis to monitor the development of symptoms of diabetes mellitus.

Metformin with monotherapy does not cause hypoglycemia, but caution should be exercised when used in combination with insulin or other hypoglycemic agents (eg, sulfonylureas, insulin, repaglinide and etc.).

The use of metformin is recommended for the prevention of type 2 diabetes mellitus in patients 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.

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

Monotherapy with the drug metformin does not cause hypoglycemia and therefore does not affect the ability to drive vehicles and work with mechanisms. However, patients should be cautious 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 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 50, 60 or 100 tablets in cans of polymer with a lid.

Each bank or 2, 3, 4, 5, 6, 10 contour cell packs of 10 tablets with instructions for use are placed in a pack of cardboard.

Storage conditions:In a dry, protected from light place at a temperature of no higher than 25 ° C.

Shelf life:

3 years.

Keep out of the reach of children.

Terms of leave from pharmacies:On prescription

Registration number:LP-004568

Date of registration:06.12.2017

Expiration Date:06.12.2022

The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia

Manufacturer: & nbsp

MEDISORB, CJSC Russia

Information update date: & nbsp18.12.2017

Illustrated instructions

Instructions

Metformin MS (Metformin MS)