Metphorvel pills 500mg, 60pcs

Composition

Per tablet:

Active ingredient: Metformin hydrochloride-500 mg.

Excipients: pregelatinized corn starch, sodium carboxymethyl starch (sodium starch glycolate, primogel), sodium stearyl fumarate, povidone K 30 (plasdon K 29/32, collidone), talc, macrogol 6000 (polyethylene glycol 6000, polyethylene oxide 6000), shell composition: opadray 03F180011 white (hypromellose, titanium dioxide, macrogol).

Pharmacological action

Pharmacotherapeutic group: hypoglycemic agent for oral use of the biguanide group

ATX code: A 10 VA 02

Pharmacological properties

Pharmacodynamics

Metformin reduces hyperglycemia without causing hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and does not have a hypoglycemic effect in healthy individuals. Increases the sensitivity of peripheral insulin receptors and the utilization of glucose by cells. Reduces liver glucose production by inhibiting gluconeogenesis and glycogenolysis.

Delays the absorption of glucose in the intestines.

Metformin stimulates glycogen synthesis by acting on 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.

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

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 type 2 diabetes, in whom lifestyle changes did not allow achieving adequate glycemic control.

Pharmacokinetics

Absorption and distribution

After oral use, metformin is absorbed from the gastrointestinal tract quite completely. Absolute bioavailability is 50-60%. The maximum concentration (Cmax) (approximately 2 µg / ml or 15 µmol) in the blood plasma is reached after 2.5 hours. With simultaneous food intake, the absorption of metformin decreases and is delayed.

Metformin is rapidly distributed in the tissues, practically does not bind to plasma proteins.

Metabolism and elimination

It is metabolized to a very weak degree and is excreted by the kidneys. The clearance of metformin in healthy subjects is 400 ml / min (4 times greater than creatinine clearance), which indicates the presence of active tubular secretion. The elimination half-life is approximately 6.5 hours. With renal failure, it increases, and there is a risk of accumulation of metformin.

Indications

Type 2 diabetes mellitus, especially in obese patients, when diet therapy and exercise are ineffective:

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

– in children from 10 years of age as monotherapy or in combination with insulin.

Prevention of type 2 diabetes in prediabetic patients with additional risk factors for developing type 2 diabetes, in whom lifestyle changes did not allow achieving adequate glycemic control.

Use during pregnancy and lactation

Decompensated diabetes mellitus during pregnancy is associated with an increased risk of birth defects and perinatal mortality. Limited evidence suggests that taking metformin in pregnant women does not increase the risk of developing birth defects in children.

When planning pregnancy, as well as in the case of pregnancy while taking metformin for prediabetes and type 2 diabetes, the drug should be discontinued, and in the case of type 2 diabetes, insulin therapy should be prescribed. It is necessary to maintain the concentration of glucose in the blood plasma at the level closest to normal, in order to reduce the risk of fetal malformations.

Metformin passes into breast milk. No side effects were observed in newborns who were breastfed while taking metformin. 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 made taking into account the benefits of breastfeeding and the potential risk of side effects in the child.

Contraindications

– hypersensitivity to Metformin or to any accessory ingredient;

– diabetic ketoacidosis, diabetic precoma, coma;

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

acute condition of proceeding with the risk of developing kidney problems: dehydration (diarrhea, vomiting), severe infection, shock;

– symptomatic manifestations of acute or chronic diseases that may lead to the development of tissue hypoxia (including acute heart failure, chronic heart failure with unstable hemodynamic, respiratory failure, acute myocardial infarction);

– extensive surgery and trauma, when shown holding insulin (see section “Special instructions”);

– liver failure, liver dysfunction;

chronic alcoholism, acute alcohol poisoning;

– pregnancy;

– lactic acidosis (including history);

– application in less than 48 hours before and within 48 hours after the radioisotope or radiological examinations with use of iodinated contrast agents (see section “Interaction with other medicines”);

– adherence to a reduced-calorie diet (less than 1000 kcal/day).

With caution

-people over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis;

– patients with renal insufficiency (creatinine clearance 45-59 ml/min);

– breast – feeding period;

– children aged 10 to 12 years.

Side effects

The frequency of side effects was evaluated as follows: very common (≥1/10); common (≥1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (

Metabolic and nutritional disorders: very rare – lactic acidosis (see section “Special instructions”).

With prolonged use of metformin, there may be a decrease in the absorption of vitamin B12. If megaloblastic anemia is detected, it is necessary to consider the possibility of such an etiology.

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

Gastrointestinal disorders: very common – nausea, vomiting, diarrhea, abdominal pain and lack of appetite.

Most often, they occur during the initial period of treatment and in most cases pass spontaneously. To prevent symptoms, it is recommended to take metformin 2 or 3 times a day during or after a meal. Slowly increasing the dose may improve gastrointestinal tolerance.

Skin and subcutaneous tissue disorders: very rare – skin reactions such as erythema, pruritus, rash.

Liver and biliary tract disorders: very rarely – impaired liver function and hepatitis; after discontinuation of metformin, these adverse events completely disappear.

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

Interaction

Contraindicated combinations

of iodine-containing radiopaque agents: against the background of functional renal failure in patients with diabetes mellitus, radiological examination with the use of iodine-containing radiopaque agents may cause the development of lactic acidosis. Treatment with metformin should be discontinued, depending on renal function,48 hours before or during the X-ray examination using iodine-containing radiopaque agents and not resumed earlier than 48 hours after, provided that during the examination the renal function was found to be normal.

Not recommended combinations

Alcohol: acute alcohol intoxication increases the risk of lactic acidosis, especially in the case of:

– insufficient nutrition, compliance with a low-calorie diet;

– liver failure.

While taking the drug, you should avoid taking alcohol and drugs containing ethanol.

Combinations that require caution

Danazol: simultaneous use of danazol is not recommended in order to avoid the hyperglycemic effect of the latter. If treatment with danazol is necessary and after discontinuation of the latter, it is necessary to adjust the dose of metformin under the control of blood glucose concentration.

Chlorpromazine: when taken in large doses (100 mg per day) increases the concentration of glucose in the blood, reducing the release of insulin. During treatment with neuroleptics and after discontinuation of the latter, it is necessary to adjust the dose of metformin under the control of glucose concentration.

Glucocorticosteroids (corticosteroids) of systemic and local action reduce glucose tolerance, increase the concentration of glucose in the blood, sometimes causing ketosis.During the treatment of corticosteroids and after discontinuation of the latter, it is necessary to adjust the dose of metformin under the control of glucose concentration.

Diuretics: concomitant use of loop diuretics may lead to lactic acidosis due to possible functional renal failure. Metformin should not be used if creatinine clearance is below 60 ml/min.

Injectable beta-2-adrenomimetics: increase the concentration of glucose in the blood 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 use of insulin is recommended.

With the simultaneous use of the above medications, more frequent monitoring of blood glucose concentrations may be required, especially at the beginning of treatment. If necessary, the dose of metformin can be adjusted during treatment and after discontinuation.

Antihypertensive drugs, with the exception of angiotensin-converting enzyme inhibitors, can reduce the concentration of glucose in the blood. If necessary, the metformin dose should be adjusted.

Concomitant use of metformin with sulfonylurea derivatives, insulin, acarbose, and salicylates may lead to hypoglycemia.

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.

The hypoglycemic effect of metformin can be reduced by phenothiazides, glucagon, estrogens, contraceptives, phenytoin, sympathomimetics, nicotinic acid, isoniazid, slow calcium channel blockers, levothyroxine sodium.

Concomitant use with cimetidine reduces the rate of elimination of metformin, which can lead to the development of lactic acidosis.

In healthy volunteers, no changes in their pharmacokinetic parameters were observed when metformin and propranolol were co-administered, as well as when metformin and ibuprofen were used.

Metformin may reduce the effect of indirect anticoagulants. Substrates of organic cation transporter 1 and 2 (OST 1 and OST 2) Metformin is a substrate of organic cations OST 1 and OST 2.

When combined with metformin:

– OST 1 inhibitors (such as verapamil) may reduce the hypoglycemic action of Metformin;

inductors OST 1 (such as rifampicin) may increase the absorption of Metformin in the gastrointestinal tract and enhance its hypoglycemic effect;

inhibitors OST 2 (such as cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may reduce the excretion of Metformin by the kidneys and lead to an increase in its concentration in blood plasma;

inhibitors OST 1 and OST 2 (such as krizotinib, olaparib) may reduce the hypoglycemic effect of Metformin.

How to take, course of use and dosage

They are taken orally.

Adults:

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

The usual starting dose is 500 mg or 850 mg 2-3 times a day after or during a meal.

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. A slow increase in the 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.

If you plan to switch from taking another hypoglycemic agent, you should stop taking another drug and start taking metformin at the dose indicated above.

Combination with insulin: To achieve better blood glucose control, metformin and insulin can be used as a combination therapy in patients with type 2 diabetes mellitus. The usual starting 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, the drug can be used both in monotherapy and in combination with insulin. The usual starting 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 concentration of glucose in the blood. 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 conduct 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 if there are no conditions that may increase the risk of lactic acidosis.

In patients with a 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.

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

Duration of treatment: the drug should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

Overdose

When using metformin at a dose of 85 g (42.5 times the maximum daily dose), the development of hypoglycemia was not observed, but in this case the development of lactic acidosis was noted (see the section “Special instructions”). Symptoms of lactic acidosis are: severe weakness, myalgia, abdominal pain, respiratory disorders, increased drowsiness. In severe lactic acidosis, the development of arterial hypotension and resistant bradyarrhythmia was noted.

Treatment: if signs of lactic acidosis appear, treatment with the drug should be stopped immediately, the patient should be urgently hospitalized and, after determining the lactate concentration, the diagnosis should be clarified. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also performed.

Description

Round biconvex tablets, film-coated in white or almost white color. On a cross-section – the core is white or almost white in color.

Special instructions

Lactic acidosis

Lactic acidosis is a rare but serious complication (high mortality in the absence of urgent treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis during metformin use occurred mainly in patients with diabetes mellitus with severe renal insufficiency.

Other associated risk factors should also be considered, such as uncompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure, and any condition associated with severe hypoxia. This can help reduce the incidence of lactic acidosis.

The risk of developing lactic acidosis should be considered if there are non-specific 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 parameters are a decrease in blood pH (less than 7.25), a concentration of lactate in blood plasma over

5 mmol / l, an increased anion gap and the ratio of lactate/pyruvate. If metabolic acidosis is suspected, stop taking the drug and immediately consult a doctor.

Surgical operations

The use of metformin should be discontinued 48 hours before elective surgery and may be continued no earlier than 48 hours after, provided that renal function was found to be normal during the examination.

Kidney function

Since metformin is excreted by the kidneys, before starting treatment and regularly thereafter, it is necessary to determine creatinine clearance:

– 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 normal.

If creatinine clearance is less than 45 ml / min, the drug is contraindicated. Special care should be taken in the event of possible renal impairment in elderly patients, with the simultaneous use of antihypertensive drugs, diuretics or nonsteroidal 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 have their heart function and kidney function monitored regularly while taking metformin.

Metformin is contraindicated in patients with heart failure and unstable hemodynamic parameters.

Children and adolescents

The diagnosis of type 2 diabetes should be confirmed before starting treatment with metformin.

In clinical trials lasting 1 year, metformin was shown to have no effect on growth and puberty. However, due to the lack of long-term data, careful monitoring of the subsequent effect of metformin on these parameters in children, especially during puberty, is recommended.

The most careful monitoring is necessary for children aged 10-12 years.

Other precautions

-Patients are advised to continue to follow a diet with a uniform intake of carbohydrates throughout the day. Overweight patients are recommended to continue to follow a hypocaloric diet (but not less than 1000 kcal / day).

– Patients should inform the doctor about any ongoing treatment and any infectious diseases.

– It is recommended to regularly perform standard laboratory tests to control diabetes mellitus.

– Metformin alone does not cause hypoglycemia, but caution is recommended when used in combination with insulin or other hypoglycemic agents (for example, sulfonylureas, repaglinide, etc. ).

Metformin is recommended for the prevention of type 2 diabetes in individuals with prediabetes and additional risk factors for overt type 2 diabetes, such as::

– age less than 60 years;

– body mass index (BMI) ≥35 kg/m2;

– gestational diabetes mellitus in the anamnesis;

– family history of diabetes mellitus in relatives of the first degree;

– increased triglyceride concentration;

– reduced HDL cholesterol concentration;

– arterial hypertension.

Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, visual impairment, or impaired concentration.

Influence on the ability to drive vehicles and mechanisms Metformin monotherapy does not cause hypoglycemia, so it does not affect the ability to drive vehicles and mechanisms.

However, patients should be warned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylureas, insulin, repaglinide, etc. ).

Storage conditions

In a place protected from light at a temperature not exceeding 25 ° C. Keep out of reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Metformin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets