Merifatin - instructions for use, doses, side effects, contraindications

Active substance: metformin hydrochloride 500 mg / 850 mg / 1000 mg. Excipients: hypromellose 2208 5.0 mg / 8.5 mg / 10.0 mg; povidone K90 (kollidone 90F) 20.0 mg / 34.0 mg / 40.0 mg; sodium stearyl fumarate 5,0 mg / 8.5 mg / 10.0 mg.

Film water-soluble shell: hypromellose 2910 7,0 mg / 11.9 mg / 14.0 mg; polyethylene glycol 6000 (macrogol 6000) 0.9 mg / 1.53 mg / 1.8 mg; polysorbate 80 (Tween 80) 0.1 mg / 0.17 mg / 0.2 mg; titanium dioxide 2.0 mg / 3.4 mg / 4.0 mg.

Description:

Tablets 500 mg: oblong biconvex tablets, covered with a film coating of white color. On the cross section, the nucleus is white or almost white in color.

Tablets 850 mg: oval biconvex tablets, covered with a film coating of white color.On the cross-section of the tablet the nucleus is white or almost white in color.

Tablets 1000 mg: oblong biconvex tablets, covered with a film shell of white color with a risk on one side. On the core is white or almost white in color.

Pharmacotherapeutic group:The hypoglycemic agent of the biguanide group for oral administration

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 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 metformin for the prevention of diabetes mellitus in patients with prediabetes with additional risk factors for the development of overt diabetes mellitus type 2, in whom lifestyle changes did not allow adequate glycemic control.

Pharmacokinetics:

Absorption and distribution

After oral administration metformin absorbed from the gastrointestinal tract quite fully. Absolute bioavailability is 50-60%. Maximum concentration (FROMmOh) (about 2 mcg / 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 patients with obesity, 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 at a risk of developing renal dysfunction: dehydration (with diarrhea, vomiting), severe infectious diseases, 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");

- liver failure, a violation of liver function;

- chronic alcoholism, acute alcohol poisoning;

- Pregnancy;

- lactic acidosis (including in the anamnesis);

- use less than 48 hours before and within 48 hours after radioisotope or X-ray studies with the introduction of an iodine-containing contrast medium (see section "Interaction with other drugs");

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

Carefully:

Apply the drug

- 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 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 with prediabetes and type 2 diabetes, the drug should be canceled, and in case of diabetes mellitus Type 2 is prescribed by insulin therapy. It is necessary to maintain the level 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 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 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.

Adults:

Monotherapy and combination therapy in combination with other oral hypoglycemic agents for 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. 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 receiving metformin in doses of 2000-3000 mg / day, can be transferred to receive the drug Merifatin 1000 mg. The maximum 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 medication and start taking the 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, while 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 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 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 renal function, the dose of metformin should be selected under regular monitoring of renal function (to determine the concentration of serum creatinine at least 2-4 times a year).

Duration of treatment

Metformin should be taken 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 often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000).

Side effects are presented in order of decreasing importance.

From the side of 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.

From the nervous system: often - a violation of taste.

From the gastrointestinal tract: very often - nausea, vomiting, diarrhea, abdominal pain, 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.

From the skin and subcutaneous tissue: very rarely skin reactions such as erythema, pruritus, rash.

Disorders from the liver and bile ducts: very rarely a violation of liver function or hepatitis; after the withdrawal of metformin, these undesirable phenomena completely disappear. Published data, post-marketing data, and 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:

When metformin was used in a dose of up to 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 below)."Special instructions").

Treatment: in the case of signs of lactic acidosis, treatment with the drug must be stopped immediately, the patient immediately 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 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: acute alcohol intoxication increases risk development of lactic acidosis, especially in the following cases:

- malnutrition, compliance with a low-calorie diet;

- hepatic insufficiency.

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

Combinations that require caution

Danazol: It is not recommended simultaneous reception of danazolum in order to avoid hyperglycemic action of the latter. If it is necessary to treat danazol and after stopping the latter, a dose adjustment of metformin is required under the control of the glucose concentration 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, correction of the dose of metformin is required under the control of 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.Do not assign metformin, if the creatinine clearance is less than 60 ml / min.

Assigned as injections of beta2-adrenomimetics: increase the concentration of glucose in the blood due to stimulation of beta2-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 glucose in blood, 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. If necessary, the dose of metformin should be adjusted. With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose, salicylates may develop 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.

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. 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. 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 the lower limit of the norm.

When the creatinine clearance is 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, while using antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

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 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).

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

- Metformin when monotherapy does not cause hypoglycemia, but it is advisable to use caution when used in combination with insulin or other hypoglycemic agents (for example, sulfonylurea derivatives, repaglinide, etc.).

The use of metformin is recommended for the prevention of type 2 diabetes mellitus to persons with prediabetes and additional risk factors for the development of overt diabetes mellitus type 2, such as:

- age 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 metformin does not cause hypoglycemia and therefore does not affect the ability to drive vehicles and mechanisms. However, 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, 1000 mg.

Packaging:

Primary packaging of medicinal product

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 15, 30, 60, 100, 120 tablets in a polymer can of polyethylene with a cover pulled with the control of the first opening. Free space is filled with cotton wool. Labels are applied to cans from paper label or writing, or from polymer materials, self-adhesive.

Secondary packaging of medicinal product

By 1, 2, 3, 4, 5, 6, 8, 9 or 10 contour mesh packages together with the instruction for use are placed in a pack of cardboard for consumer containers.

On 1 bank together with the instruction on application place in a pack from a cardboard for consumer tare.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004363

Date of registration:05.07.2017

Expiration Date:05.07.2022

The owner of the registration certificate:Pharmasintez-Tyumen, Open CompanyPharmasintez-Tyumen, Open Company Russia

Manufacturer: & nbsp

FARMASINTEZ, JSC (Irkutsk) Russia

Pharmasintez-Tyumen, Open Company Russia

Information update date: & nbsp06.09.2017

Illustrated instructions

Instructions

Merifatin (Merifatin)