Metformin MS tablets p / o 500mg, No. 60

• Diabetes mellitus type 2 (non-insulin dependent) with ineffective diet therapy and exercise, in obese patients:

  • in adults - as monotherapy or in combination with other oral hypoglycemic agents or with insulin;

  • in children aged 10 years and older - as monotherapy or in combination with insulin.

Administered orally, swallowing without chewing, during or immediately after a meal, drinking plenty of water.

Adults:

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

The usual starting dose is 500 or 850 mg 2-3 times daily after or during a meal. It is recommended to adjust the dose every 10-15 days based on the results of measuring the concentration of glucose in the blood plasma. A slow increase in dose helps to 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 taking metformin at doses of 2000-3000 mg / day can be switched to receiving metformin 1000 mg. The maximum recommended dose is 3000 mg per day, divided into three doses.

If you are planning to switch from taking another hypoglycemic agent: you must stop taking the other drug and start taking the drug metformin at the dose indicated above.

Combination with insulin:

To achieve better control of plasma glucose, metformin and insulin in patients with type 2 diabetes mellitus can be used in combination therapy. The usual starting dose of metformin is 500 mg or 850 mg 2-3 times a day after or during a meal, while the dose of insulin is adjusted based on the blood glucose concentration.

Children and adolescents:

In children from 10 years of age, metformin can be used both in monotherapy and in combination with insulin. The usual starting dose is 500 or 850 mg once daily after or during a meal. After 10-15 days, the dose must be adjusted based on the blood glucose concentration. The maximum daily dose is 2000 mg, divided into 2-3 doses.

Monotherapy for prediabetes:

The usual dose is 1000-1700 mg per day after or during a meal, divided into 2 doses.

It is recommended to regularly carry out glycemic control to assess the need for further use of the drug.

Patients with renal impairment:

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 of 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. Kidney function should be closely monitored (every 3-6 months).

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

Elderly patients:

Due to a possible decrease in renal function, the dose of metformin must be selected under regular monitoring of renal function indicators (determination of creatinine concentration in blood plasma at least 2-4 times a year).

Duration of treatment:

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

Active substance:

metformin hydrochloride - 500 mg

Excipients: potato starch, povidone (K-30), talc, magnesium stearate.

The composition of the film shell: OPADRYЃ II: hypromellose (HPMC 2910), lactose monohydrate, titanium dioxide, macrocode, iron oxide red.

• Acute or chronic metabolic acidosis, diabetic ketoacidosis, diabetic precoma, and coma;

• renal failure, impaired renal function (CC <60 ml / min);

• dehydration, severe infection, hypoglycemic shock, which can lead to impaired renal function;

• clinically pronounced symptoms of acute and chronic diseases that can lead to the development of tissue hypoxia (including heart failure, acute myocardial infarction, respiratory failure);

• the use of contrasting iodine-containing substances for intravascular administration (including when performing intravenous urography, intravenous cholangiography, angiography, CT);

• acute alcohol intoxication, chronic alcoholism;

• hypersensitivity to metformin.

pharmachologic effect

Oral hypoglycemic agent from the biguanide group (dimethylbiguanide). The mechanism of action of metformin is associated with its ability to suppress gluconeogenesis, as well as the formation of free fatty acids and fat oxidation. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Metformin does not affect the amount of insulin in the blood, but changes its pharmacodynamics by reducing the ratio of bound to free insulin and increasing the ratio of insulin to proinsulin.

Metformin stimulates glycogen synthesis by acting on glycogen synthetase. Increases the transport capacity of all types of membrane glucose transporters. Delays the absorption of glucose in the intestine.

Reduces the level of triglycerides, LDL, VLDL. Metformin improves the fibrinolytic properties of blood by inhibiting tissue-type plasminogen activator inhibitor.

While taking metformin, the patient's body weight either remains stable or decreases moderately.

Pharmacokinetics

After oral administration, metformin is slowly and incompletely absorbed from the gastrointestinal tract. Cmax in plasma is reached after about 2.5 hours. With a single dose of 500 mg, the absolute bioavailability is 50-60%. With the simultaneous intake of food, the absorption of metformin is reduced and delayed.

Metformin is rapidly distributed into body tissues. Practically does not bind to plasma proteins. It accumulates in the salivary glands, liver and kidneys.

It is excreted by the kidneys unchanged. T1 / 2 from plasma is 2-6 hours.

In case of impaired renal function, the accumulation of metformin is possible.

Side effect

From the digestive system: possible (usually at the beginning of treatment) nausea, vomiting, diarrhea, flatulence, abdominal discomfort; in isolated cases - impaired liver function indicators, hepatitis (disappear after stopping treatment).

From the side of metabolism: very rarely - lactic acidosis (discontinuation of treatment is required).

From the side of the hematopoietic system: very rarely - impaired absorption of vitamin B12.

The profile of adverse reactions in children aged 10 years and older is the same as in adults.

Application during pregnancy and lactation

There have been no adequate and well-controlled studies on the safety of metformin during pregnancy. Use during pregnancy is possible in cases of extreme necessity, when the expected benefit of therapy to the mother outweighs the possible risk to the fetus. Metformin crosses the placental barrier.

Metformin in small amounts is excreted in breast milk, while the concentration of metformin in breast milk can be 1/3 of the concentration in the mother's plasma. Side effects in newborns with breastfeeding while taking metformin were not observed. However, due to the limited amount of data, use during breastfeeding is not recommended. The decision to stop breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the baby.

Preclinical studies have shown that metformin does not have a teratogenic effect in doses that are 2-3 times higher than the therapeutic doses used in humans. Metformin has no mutagenic potential and does not affect fertility.

Application for violations of liver function

Contraindicated in severe liver dysfunction.

Application for impaired renal function

Contraindicated in severe renal impairment.

Use in elderly patients

It is not recommended to use metformin in patients over 60 years old, which is associated with an increased risk of lactic acidosis.

special instructions

Not recommended for use in acute infections, exacerbation of chronic infectious and inflammatory diseases, trauma, acute surgical diseases, the risk of dehydration.

Do not use before surgery and within 2 days after surgery.

Care should be taken to use metformin in elderly patients and those performing heavy physical work, which is associated with an increased risk of lactic acidosis. In elderly patients, asymptomatic renal dysfunction is often observed. Particular care is required if renal impairment is triggered by taking antihypertensive drugs or diuretics, as well as NSAIDs.

If, during treatment, the patient has muscle cramps, indigestion (abdominal pain) and severe asthenia, then it should be borne in mind that these symptoms may indicate the onset of lactic acidosis.

During the period of treatment, it is necessary to monitor kidney function; determination of the lactate content in plasma should be carried out at least 2 times a year, as well as when myalgia appears.

When metformin is used as monotherapy in accordance with the dosing regimen, hypoglycemia usually does not occur. However, when combined with insulin or sulfonylurea derivatives, there is a risk of hypoglycemia. In such cases, it is necessary to especially carefully monitor the concentration of glucose in the blood.

During the period of treatment, patients should avoid drinking alcohol because of the risk of developing lactic acidosis.

Drug interactions

With simultaneous use with sulfonylurea derivatives, acarbose, insulin, salicylates, MAO inhibitors, oxytetracycline, ACE inhibitors, with clofibrate, cyclophosphamide, the hypoglycemic effect of metformin may increase.

With simultaneous use with GCS, hormonal contraceptives for oral administration, danazol, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, thiazide diuretics, nicotinic acid derivatives, it is possible to reduce the hypoglycemic effect of metformin.

In patients receiving metformin, the use of iodine-containing contrast agents for the purpose of diagnostic studies (including intravenous urography, intravenous cholangiography, angiography, CT) increases the risk of developing acute renal dysfunction and lactic acidosis. These combinations are contraindicated.

Beta2-adrenergic agonists in the form of injections increase the concentration of glucose in the blood due to the stimulation of ?2-adrenergic receptors. In this case, it is necessary to control the concentration of glucose in the blood. It is recommended to prescribe insulin if necessary.

Concomitant use of cimetidine may increase the risk of developing lactic acidosis.

Concomitant use of loop diuretics can lead to the development of lactic acidosis due to possible functional renal failure.

Concomitant use with ethanol increases the risk of developing lactic acidosis.

Nifedipine increases the absorption and Cmax of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin) secreted in the renal tubules compete with metformin for tubular transport systems and can lead to an increase in its Cmax.