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

Metformin is a representative of the biguanide class, which act mainly by reducing the production of endogenous glucose in the liver. Metformin reduces both basal and postprandial glucose concentrations in plasma. It does not stimulate the secretion of insulin and therefore does not cause hypoglycemia.

There are three possible mechanisms of action of metformin: a decrease in the production of glucose in the liver by suppressing gluconeogenesis and glycogenolysis; increased sensitivity of muscle tissue to insulin, increased consumption and utilization of glucose by peripheral tissues; delayed absorption of glucose from the intestine.

Metformin stimulates intracellular synthesis of glycogen, activating the enzyme glycogen synthase. It enhances the activity of all types of transmembrane glucose transporters. Metformin improves lipid metabolism - reduces the concentration of total cholesterol, low-density lipoprotein cholesterol and triglycerides.

Pharmacokinetics:

Suction

After oral administration metformin quickly and fairly fully absorbed from the gastrointestinal tract. Absolute bioavailability with fasting is 50-60%. The maximum concentration of the drug in plasma (C_mOh) 4 μg / ml. The time to reach the maximum concentration (T_mOh) for approximately 2.5 hours. With the simultaneous administration of the drug with food, the degree of absorption of metformin is reduced and the absorption rate decreases somewhat. After ingestion of metformin in a dose of 850 mg while eating it C_mOh decreases by 40% and the area under the curve "concentration-time" (AUC) - by 25%, T_mOh increases by 35 min. The clinical significance of these changes is not known.

Distribution

Metformin is rapidly distributed into tissues, practically does not bind to plasma proteins. Penetrates into red blood cells. The volume of distribution is 63-276 liters.

Metabolism

Exposed to a very weak degree of metabolism.

Excretion

It is excreted by the kidneys, mostly unchanged. The clearance of metformin in healthy subjects is 400 ml / min. Half-life (T_1/2) about 6.5 hours.

If renal function is impaired, the renal clearance of metformin decreases in proportion to the decrease in creatinine clearance (CC) and, therefore, increases T_1/2, as a result, there is a risk of cumulation of metformin.

Indications:

Diabetes mellitus type 2 in adults (especially in obese patients) with ineffectiveness of diet and exercise, as a monotherapy or in combination with other oral hypoglycemic agents or insulin.

Diabetes mellitus type 2 in children with 10 years as a monotherapy or combination with insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance;

- diabetic ketoacidosis, diabetic precoma, coma;

- kidney failure or renal dysfunction (KK <60 ml / min);

- acute conditions that occur with a risk of developing renal dysfunction:

dehydration (with diarrhea, vomiting), fever, severe infectious diseases;
the state of hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases);

- clinically pronounced manifestations of acute and chronic diseases that can lead to the development of tissue hypoxia (including cardiac or respiratory failure, acute myocardial infarction);

- hepatic failure, impaired liver function;

- chronic alcoholism, acute alcohol poisoning;

- lactic acidosis (including and in the anamnesis);

- application for at least 48 hours before and within 48 hours after carrying out radioisotope or radiographic studies with the introduction of iodine-containing contrast medium (see section "Interaction with other drugs");

- period not less than 48 hours before and within 48 hours after surgical interventions under general anesthesia, spinal or epidural anesthesia;

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

- children under 10 years old.

Carefully:

If you have any of these diseases, consult a doctor before taking the drug.

In persons over the age of 60, performing heavy physical work (increased risk of lactic acidosis).

Pregnancy and lactation:

At present, there is insufficient data on the use of the drug in pregnant women with diabetes mellitus. Pregnant women or women planning to become pregnant should not use the drug.

It is not known whether the drug penetrates into breast milk. Nursing women are advised not to use the drug, or, if necessary, to take it, stop breastfeeding.

Dosing and Administration:

Adults

Monotherapy and combination with others oral hypoglycemic drugs

The initial dose is 1 tablet 2-3 times a day during or after a meal.

After 10-15 days of therapy, the dose of the drug should be adjusted, based on blood glucose. A gradual increase in the dose reduces the risk of developing adverse events from the gastrointestinal tract.

The maximum recommended dose is 3000 mg / day.

If it is necessary to transfer the patient from other oral hypoglycemic drugs to metformin, you must first stop taking previously taken medications, and then start therapy with metformin.

Combination with insulin

Metformin and insulin can be taken in combination under careful control of glucose concentration. In this case, the dose metformin is not different from the usually recommended - 1 tablet 2-3 times a day, and the dose of insulin depends on the glucose concentration in the blood.

Elderly patients

Given the possibility of developing a violation of kidney function in this category of patients, it is necessary to adjust the dose of the drug depending on the indicators of kidney function.

Children and teens

Monotherapy or in combination with insulin

Metformin Sandoz® can be used in children from 10 years.

The initial dose is 500 mg 1 time per day during or after a meal. After 10-15 days of therapy, the dose of the drug should be adjusted, based on blood glucose. Gradual increase in dose reduces the risk of adverse events from the side gastrointestinal tract. The maximum recommended dose is 2000 mg / day in 2-3 doses.

Side effects:

The frequency of adverse reactions is presented according to the following gradation: 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 and individual reports).

From the gastrointestinal tract: very often - nausea, vomiting, diarrhea, abdominal pain, lack of appetite, flatulence; often a metallic taste in the mouth.

From the skin of the subcutaneous tissue: very often - skin reactions (such as: rash, itching, urticaria, erythema).

From the hepatobiliary system: in some cases - deviation of liver function indicators or hepatitis, which occur after the drug is discontinued.

Other: very often - with prolonged use of the drug, a decrease in the concentration of vitamin and folate in the serum, which in very rare cases can lead to the development of megaloblastic anemia; very rarely - lactic acidosis.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Overdose of metformin (or concomitant risk factors for lactic acidosis) can lead to the development of lactic acidosis.

Treatment: lactic acidosis is an urgent medical condition and requires treatment in a hospital. To remove lactate and metformin from the body, hemodialysis should be used.

Interaction:

Alcohol

In acute alcohol intoxication against the background of metformin treatment, the risk of lactic acidosis increases, especially in cases of concomitant conditions:

- prolonged starvation or exhaustion

- liver failure

It is recommended to avoid joint admission Metformin Sandoz® and preparations containing ethanol.

Cimetidine

The interaction of metformin and cimetidine leads to inhibition of renal excretion of metformin. It is not recommended to take these drugs together.

Iodine-containing radiopaque substances

Intravascular injection of iodine-containing radiopaque substances can lead to the development of renal failure, which can result in the cumulation of metformin and the development of lactic acidosis. In this regard, the use of the drug should be canceled 48 hours before the start of radiography, and the resumption of metformin may be no less than 48 hours after the X-ray and on the condition of laboratory confirmation of normalkidney function.

Preparations, which require special care

With the simultaneous use of metformin with danazol may develop a hyperglycemic effect. If it is necessary to treat danazol and after stopping its intake, a dose adjustment of metformin is required under the control of the glucose concentration in the blood.

Chlorpromazine in high doses (100 mg / day) reduces the release of insulin and increases the concentration of glucose in the blood.

When used simultaneously with neuroleptics and after stopping their intake, a dose adjustment of metformin is required under the control of the glucose concentration in the blood.

Glucocorticosteroids (GCS) for parenteral and topical application reduce glucose tolerance and increase the concentration of glucose in the blood, in some cases, causing ketosis. When using this combination, and after stopping the use of GCS, a dose adjustment of metformin is required under the control of the glucose concentration in the blood.

With the simultaneous use of "loop" diuretics and metformin, there is a risk of lactic acidosis because of the possible emergence of functional renal failure.

Assignment in the form of injections of β₂-adrenomimetics reduces the hypoglycemic effect of metformin due to stimulation of β₂adrenoreceptors. In this case, you should monitor the blood glucose and, if necessary, prescribe insulin.

Angiotensin converting enzyme inhibitors and other antihypertensive drugs 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 culfonylureas, insulin, acarbose and salicylates may increase the hypoglycemic effect.

Nifedipine increases absorption and C_m_Ohmetformin, which must be taken into account when concomitant administration.

"Loopback" diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of decreased kidney function. In this case, care must be taken when applying metformin.

Special instructions:

When using metformin, there is a risk of developing lactic acidosis, whose symptoms are breathing disorders, nausea, vomiting, diarrhea, abdominal pain, hypothermia, myalgia and coma development. When the symptoms described above should stop taking the drug and determine the concentration of electrolytes, lactate in the blood, the pH value.Lactic acidosis is a life threatening condition and requires immediate discontinuation of the drug and intensive treatment in a hospital setting. The most effective method of treatment is hemodialysis.

Insufficiently controlled diabetes mellitus, excessive alcohol consumption, prolonged fasting, ketonemia, liver failure and all conditions accompanied by hypoxia, against the background of metformin use increase the risk of lactic acidosis.

As metformin is allocated by the kidneys, it is necessary to determine the concentration of creatinine in the blood before the start of therapy and regularly the treatment process:

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

- at least 2-4 times a year in patients with a concentration of creatinine exceeding the norm, and in elderly patients (because the decrease in renal function in elderly patients develops often enough and is asymptomatic)

If surgical intervention is required under general anesthesia, the drug should be discontinued 48 hours before the intervention and the drug can be resumed no earlier than 48 hours after the procedure.

When prescribing the drug for children from 10 years old, diagnosis of type 2 diabetes must be confirmed before the start of therapy.

When administering the drug, all patients should continue to follow the diet, and they need to regularly monitor the fasting glucose and after eating and glycosylated hemoglobin HbAlc.

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

The drug, taken in the form of monotherapy, does not reduce the ability to concentrate, but against the background of its use with other hypoglycemic drugs (derivatives of sulfonylureas, insulin, repaglinide) it is possible to develop hypoglycemic conditions, in which the ability to drive vehicles and engage in other potentially dangerous activities that require increased attention and rapid psychomotor reactions deteriorates.

Form release / dosage:

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

Packaging:

For tablets with a dosage of 500 mg and 850 mg: 10 tablets, film-coated, in PVC / Al. blister; for 3, 6 or 12 blisters together with instructions for use in a cardboard box.

For tablets with a dosage of 1000 mg: 15 tablets, film-coated, in PVC / Al. blister; for 2, 4 or 8 blisters together with instructions for use in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-000747

Date of registration:29.09.2011 / 06.05.2016

Expiration Date:29.09.2016

Date of cancellation:2016-11-28

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

LEK, S.A. Poland

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp12.05.2018

Illustrated instructions

Instructions

Metformin Sandoz® (Metformin Sandoz®)