Metformin-Borimed

General characteristics. Structure:

Active ingredient: 500 mg, 850 mg or 1000 mg of Metforminum of a hydrochloride.

Excipients: starch 1500, povidone, croscarmellose sodium, magnesium stearate, cellulose microcrystallic, опадрай II (contains: polyvinyl alcohol, Makrogol 3350, talc, titanium dioxide (E 171), indigo carmine (Е 132), yellow quinolinic (Е 104)).

Pharmacological properties:

Pharmacodynamics. Hypoglycemic means from group of guanyl guanidines. Reduces concentration of glucose in blood by oppression of a gluconeogenesis, reduction of absorption of glucose from digestive tract and increase in its utilization by peripheral fabrics (muscular and fatty).

Reduces concentration in serum of triglycerides, cholesterol and lipoproteins of low density and does not change concentration of lipoproteins of high density. Stabilizes or reduces body weight.

At absence in insulin blood the therapeutic effect is not shown. Does not provoke development of hypoglycemic reactions. Connected/free insulin reduces a ratio, insulin/pro-insulin raises a ratio.

At patients with a metabolic cardiovascular syndrome (a syndrome of X) Metforminum reduces arterial pressure at night and promotes recovery of its day-night rhythm.

Improves fibrinolitic properties of blood due to suppression of inhibitor of the activator of plasminogen (plasminogen) of fabric type.

Pharmacokinetics. After intake it is quickly soaked up in a GIT. Absolute bioavailability on an empty stomach makes 50-60%.

The maximum concentration (Cmax) is reached approximately in 2,5 h, reception with food lowers Cmax by 40% and slows down its achievement for 35 min. Concentration in plasma does not exceed 1 mkg/ml.

The volume of distribution (Vd) makes 296 - 1012 l. Communication with proteins of plasma insignificant, it is capable to collect in erythrocytes.

Elimination half-life (Т½) about 6,5 h (initial Т½ from 1,7 to 3 h, terminal – from 9 to 17 h). The renal clearance makes more than 400 ml/min.

It is removed by kidneys, it is preferential in not changed look (glomerular filtering and canalicular secretion) and through intestines (to 30%).

At a renal failure the clearance decreases in proportion to clearance of creatinine. Т½ there is a risk of cumulation of medicine and concentration of Metforminum in plasma increases.

Indications to use:

Diabetes mellitus like II at adults (non-insulin-dependent) (including at inefficiency of a dietotherapy), especially in the cases which are followed by obesity – in the form of monotherapy, and also in combination with drugs of sulphonylurea and glitazon.

In a combination with insulin – at a diabetes mellitus of the II type in case of secondary resistance to insulin and a gross obesity.

Complex therapy of obesity (including alimentary, at diseases of a hypophysis, a Pickwickian syndrome).

Route of administration and doses:

The dose is established individually depending on glucose level in blood. Accept inside, in time or directly after food, without chewing, washing down with enough liquid.

To the patients who are not receiving insulin, Metformin-Borimed appoint 500–1000 mg (1 tablet on 500 mg or 850 mg; or 2 tablets on 500 mg, or 1 tablet on 1000 mg) 2 times a day in the first week; depending on glycemia level a dose 3 times a day increase at an interval of 1 week by 500 mg/days to a dose 1000 mg (2 tablets on 500 mg or 1 tablet on 1000 mg). Duration of use is defined by the doctor. The supporting daily dose – 1000-2000 mg/days (2 - 4 tablets on 500 mg or 2 tablets on 850 mg, or 2 tablets on 1000 mg).

The maximum daily dose - 3 g (6 tablets on 500 mg or 3 tablets on 1000 mg, or 3 tablets on 850 mg). At patients of advanced age the recommended single dose should not exceed 850 mg. At children 10 years an initial dose of 500 mg 2-3 times a day after food or on meal time with dose adjustment in 10 - 15 days on the basis of measurement of level of glucose in blood are aged more senior. The maximum daily dose for children of 2000 mg divided into 2 - 3 receptions.

At use with insulin in doses less than 40 PIECES/days the mode of dosing of medicine same as at monotherapy, at the same time the dose of insulin can be reduced gradually (on 4 - 8 PIECES/days every other day). At an insulin dose more than 40 PIECES/days use Metformin-Borimeda and a dose decline of insulin are carried out in a hospital, the usual initial dose makes 500 - 850 mg 2 - 3 times a day, or 1000 mg of 1 times a day.

At treatment of alimentary obesity as a part of complex therapy against the background of the mode of exercise stresses in a dose of 1000 - 2000 mg (1 - 2 tablet on 1000 mg) in one step in days.

Features of use:

At treatment control of function of kidneys is necessary; definition of a lactate in plasma it is necessary to carry out at least 2 times a year, and also at emergence of a mialgiya.

Appointment at danger of dehydration is not recommended.

Researches using intravenously X-ray contrast means, surgical interventions and injuries, extensive burns, infectious diseases with a feverish syndrome can demand cancellation of peroral hypoglycemic means and purpose of insulin. An insulin therapy is begun in 2 days prior to surgical intervention or radiological inspection and continued within not less than 2 days after it.

At the combined use with derivatives of sulphonylurea careful control of a glycemia is necessary. The combined use with insulin is recommended to be carried out in a hospital.

Influence on ability to driving of motor transport and to control of mechanisms. At a medicine combination to other hypoglycemic drugs (sulphonylurea derivatives, insulin) development of hypoglycemic states at which ability to control of motor transport and to other potentially dangerous types of activity requiring special attention and speed of psychomotor reactions worsens is possible.

Side effects:

From the alimentary system: in an initiation of treatment - nausea,

vomiting, "metal" smack in a mouth, a loss of appetite, dyspepsia, a meteorism, an abdominal pain. These side effects can be reduced by gradual increase in a dose of Metforminum, at its inclusion in time or after food.

From gepato-biliary system: single messages on an abnormal liver function, medicinal hepatitises, after Metforminum cancellation these manifestations quickly disappear.

From a metabolism: in some cases (at overdose, existence of the diseases listed in the section "Contraindications", alcoholism) - lactoacidosis. At prolonged use the B12 vitamin absorption disturbance which usually does not have clinical value, quickly taking place at the therapy termination by Metforminum.

From bodies of a hemopoiesis: seldom - megaloblastny anemia.

Allergic reactions: very seldom – an erythema, an itch, skin rash.

In cases of emergence of side effects the dose should be reduced or to cancel temporarily.

Interaction with other medicines:

It is incompatible with ethanol, loopback diuretics, iodinated X-ray contrast means as increases risk of lactoacidosis, especially in cases of starvation or a low-calorie diet. During use of Metforminum it is necessary to avoid the use of alcoholic beverages and the medicinal substances containing alcohol. When carrying out X-ray inspection medicine needs to be cancelled for 48 h and not to renew within 2 days after carrying out a research.

With care to appoint in combination with indirect anticoagulants and Cimetidinum. Sulphonylurea derivatives, insulin, acarbose, inhibitors of a monoaminooxidase (MAO), Oxytetracyclinum, inhibitors of an angiotensin-converting enzyme (APF), Clofibratum, cyclophosphamide and salicylates strengthen effect of metformin.

At simultaneous use with the glucocorticosteroids, injection beta-adrenergic agonists combined by oral contraceptives, danazoly, Epinephrinum, a glucagon, thyroid hormones derivative of a fenotiazin (Chlorpromazinum), niacin, thiazide diuretics reduction of effect of metformin is possible.

Nifedipine increases absorption, Cmax, slows down removal.

Cationic substances (amiloride, digoxin, morphine, procaineamide, quinidine, quinine, ranitidine, Triamterenum and Vancomycinum) compete for canalicular transport systems and at long therapy can increase Cmax by 60%.

Contraindications:

- hypersensitivity to metformin and other guanyl guanidines;

- diabetic ketoacidosis, diabetic prekoma and coma;

- a chronic renal failure (at the level of serumal creatinine men and 1,4 mg/dl have more than 1,5 mg/dl at women or clearance of creatinine less than 60 ml/min.);

- abnormal liver functions (insufficiency of function of a liver is higher than the II degree on Chayld-Pyyu);

- states which can promote development of lactoacidosis, в.т.ч. chronic heart failure, an acute myocardial infarction, breath disturbance, an acute disorder of cerebral circulation, dehydration, the use with alcohol;

- lactoacidosis (including in the anamnesis);

- hypocaloric diet (less than 1000 kcal/days);

- pregnancy and period of a lactation;

- children's age up to 10 years;

- medicine is not appointed in 2 days before surgeries, radio isotope, X-ray inspections with administration of contrast medicines and within 2 days after their carrying out.

Precautionary measures. It is not recommended to patients to appoint more senior than 60 years at intensive exercise stresses (the increased danger of development of lactoacidosis at them). The risk of development of lactoacidosis at Metforminum level in blood is highest more than 5 mkg/ml and existence of the accompanying pathology of a respiratory organs, kidneys or cardiovascular system (heart failure). The main sign of development of lactoacidosis is increase in level of a lactate of serum more than 5 mmol/l, decrease рН blood, against the background of electrolytic disturbances and increase in the relation lactate/pyruvate. At identification at the patient of a metabolic acidosis in lack of symptoms of ketoacidosis (a ketonuria and a ketonemiya) it is necessary to cancel immediately reception of Metforminum and to control lactate level in the patient's organism.

Overdose:

Symptoms: the hypoglycemia at use of Metforminum in doses to 85 g/days is not observed. However lactoacidosis develops. Early symptoms are the expressed weakness, respiratory disturbances, drowsiness, nausea, vomiting, diarrhea, abdominal pains, a hypothermia, a lowering of arterial pressure, a reflex bradyarrhythmia, muscle pains, breath increase, dizziness, disturbance and a loss of consciousness and development of a coma is possible further.

Treatment: at emergence of symptoms of lactoacidosis treatment by Metforminum needs to be stopped, the patient urgently to hospitalize, define concentration of a lactate. The hemodialysis is most effective for removal from an organism of a lactate and Metforminum. If necessary carry out symptomatic therapy (intravenously hydrosodium carbonate, hypotonic salt solution of sodium chloride).

Storage conditions:

In the place protected from light and moisture, at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to apply medicine after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 tablets in a blister strip packaging; in packaging No. 10 x 3.