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

White, oval, biconvex tablets, film-coated, with a risk of both sides and engraving "1000" on the one hand. On the cross-section - a homogeneous white mass.

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. Raises the 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 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 the preparation Glucophage® for the prevention of diabetes mellitus in patients with prediabetes with additional risk factors for the development of overt sugartype 2 diabetes in whom lifestyle changes did not allow adequate glycemic control.

Pharmacokinetics:

Absorption and distribution

After ingestion, 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, the absorption of metformin is reduced and delayed.

Metformin is rapidly 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 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 obese patients, 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 that occur with risk of developing a violation kidney function: dehydration (with diarrhea, vomiting), severe infectious diseases, shock;

- clinically expressed manifestations of acute or chronic diseases that can lead to the development of tissue hypoxia (including acute heart failure, chronic cardiac Insufficiency with unstable parameters of hemodynamics, respiratory failure, acute myocardial infarction);

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

- liver failure, abnormal liver function;

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactic acidosis (including and in the anamnesis);

- application within less than 48 h before and within 48 hours after carrying out radioisotope or X-ray studies with the introduction of iodine-containing contrast agent (see section "Interaction with other drugs");

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

Carefully:

- in persons 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);

- during the period of breast feeding.

Pregnancy and lactation:

Decompensated sugar diabetes 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 the case of type 2 diabetes, insulin therapy is prescribed. Required maintain a glucose level in the blood plasma at the level closest to normal to reduce the risk of developing 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 on the termination of breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the child.

Dosing and Administration:

Apply inside.

Adults:

Monotherapy and combination therapy in combination with other oral hypoglycemic agents in 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. For decreasing 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 to 3000 mg / day, can be transferred to receive Glucophage ® 1000 mg. Maximum the recommended dose is 3000 mg / day, divided into 3 doses.

In case of planning the transition from taking another hypoglycemic agent: it is necessary to stop taking another drug and start taking Glucophage ® 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 Glucophage® 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 the age of 10, the preparation Glucophage® 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 a meal, divided into 2 divided doses. It is recommended to carry out regular glycemic control to assess the need for further application of the drug.

Patients with renal insufficiency:

Metformin can be used in patients with renal Mr.moderate 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:

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

Duration of treatment

The drug Glucophage® follows take 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 Frequent: ≥ 1/10

Frequent: ≥ 1/100, <1/10

Infrequent: ≥ 1/1000, <1/100

Rare: ≥ 1/10 000, <1/1000

Very rare: <1/10 000

Side effect is presented in order of decreasing importance.

Disorders from the metabolism and nutrition:

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

With prolonged use of metformin, there may be a decrease in vitamin absorption AT₁₂. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

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 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), no development of hypoglycemia was observed. However, lactoacidosis was observed in this case. Significant overdose 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 should be hospitalized immediately 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

Iodinated radiopaque means: 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 Glucophage® 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 kidney function was recognized normal.

Unrecommended combinations

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

- malnutrition, adherence to a low-calorie diet;

- hepatic insufficiency.

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

Combinations that require caution

Danazol: Not recommended simultaneous reception of danazol in avoiding hyperglycemic the latter. When the need for treatment with danazol and after discontinuation of the latter requires a correction of the dose of Glucophage ® 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, 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, a correction of the dose of Glucophage® under the control of the glucose concentration in the blood is required.

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

Assigned in the form of injections beta₂- adrenomimetics: increase the blood glucose concentration due to beta stimulation₂- 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 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 medication means, except for inhibitors angiotensin-converting enzyme, may reduce concentration of glucose in the blood. If necessary, correct the dose of metformin.

With the simultaneous use of Glucophage ® with derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine enhances the absorption and FROM_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 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. Consider the risk of developing lactic acidosis when non-specific signs appear, 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 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 start of treatment and regularly in the future, 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 lower limit of the norm.

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

Caution should be exercised when possible impairment of renal function in elderly patients, with the simultaneous use of rpotent medicines, diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

Patients with cardiac insufficiency 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 indicators 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 overweight it is recommended 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 is not causes hypoglycemia, however it is recommended to exercise caution when used in combination with insulin or other hypoglycemic agents (eg, derivatives sulfonylureas, repaglinide and other).

Glucophage® is recommended for the prevention of type 2 diabetes mellitus for persons with prediabetes and additional risk factors for developing type 2 diabetes mellitus, 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 Glucophage® does not cause hypoglycemia, so it 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 and 1000 mg.

Packaging:

Film-coated tablets, 500 mg:

For 10 tablets in a blister of PVC / aluminum foil, 3 or 5 blisters together with instructions for use are placed in a cardboard box.

For 15 tablets in a blister of PVC / aluminum foil, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

For 20 tablets in a blister of PVC / aluminum foil, 3 or 5 blisters together with the instructions for use are placed in a cardboard box.

Film-coated tablets, 850 mg:

For 15 tablets in a blister of PVC / aluminum foil, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

20 tablets per blister of PVC / aluminum foil, 3 or 5 blisters together with the instructions for use are placed in a cardboard box.

Tablets, film-coated, 1000 mg:

10 tablets per blister of PVC / aluminum foil, 3, 5, 6 or 12 blisters together with the instruction for use are placed in cardboard tutu.

15 tablets per blister of PVC / aluminum foil, 2, 3 or 4 blisters together with instructions for use are placed in a cardboard box.

Blister and cardboard tutu are applied symbol "M" for protection against tampering.

Or in the case of packaging of the drug "Nanolec":

Film-coated tablets, 500 mg, 850 mg:

For 15 tablets in a blister of PVC / aluminum foil, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

For 20 tablets in a blister of PVC / aluminum foil, 3 blisters together with instructions for use are placed in a cardboard box.

Tablets, film-coated, 1000 mg:

For 15 tablets in a blister of PVC / aluminum foil,2 or 4 blisters together with instructions for use are placed in a cardboard box.

On the blister and cardboard pack we put the symbol "M" for protection from complex "NANOLEC".

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

Dosages of 500 mg and 850 mg: 5 years.

Dosage of 1000 mg: 3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014600 / 01

Date of registration:13.08.2008 / 07.08.2015

Expiration Date:Unlimited

The owner of the registration certificate:Merck Sante ca.c.Merck Sante ca.c. France

Manufacturer: & nbsp

MERCK SANTE, s.a.s. France

NANOLEC, LTD. Russia

Representation: & nbspMERK, LLCMERK, LLCRussia

Information update date: & nbsp22.04.2017

Illustrated instructions

Instructions

Glucophage® (GLUCOPHAGE®)