Глюкофаж

General characteristics. Structure:

Active agent: Metforminum a hydrochloride - 500, 850 or 1000 mg;
Excipients: povidone, magnesium stearate.
Film cover:
Dosage of 500 mg and 850 mg: gipromelloza.
Dosage of 1000 mg: опадрай pure (gipromelloza, macrogoal 400, macrogoal 8000).

Description:
Dosage of 500 mg, 850 mg:
White, round, biconvex tablets, film coated.
On cross section - homogeneous white mass.
Dosage of 1000 mg:
White, oval, biconvex tablets, film coated, with risky on both sides and an engraving "1000" on the one hand.
On cross section - homogeneous white mass.

Pharmacological properties:

Pharmacodynamics. Глюкофаж® reduces a hyperglycemia, without leading to development of a hypoglycemia. Unlike sulphonylurea derivatives, does not stimulate secretion of insulin and does not render hypoglycemic effect at healthy faces. Increases sensitivity of peripheral receptors to insulin and glucose utilization by cells. Brakes a gluconeogenesis in a liver. Absorption of carbohydrates in intestines detains. Besides, renders a favorable effect on metabolism of lipids: reduces the content of the general cholesterol, lipoproteins of low density and triglycerides.

Pharmacokinetics. After intake Metforminum is absorbed from digestive tract rather fully. Absolute bioavailability makes 50 - 60%. The maximum concentration (Cmax) (about 2 mkg/ml or 15 µmol) in plasma is reached in 2,5 h. At a concomitant use of food absorption of Metforminum decreases and late.
Metforminum is quickly distributed in fabric, practically does not contact proteins of plasma. Is exposed to metabolism in very weak degree and it is removed by kidneys.
The clearance of Metforminum at healthy subjects makes 400 ml/min. (4 times more, than clearance of creatinine) that demonstrates existence of active kanaltsiyevy secretion. The elimination half-life makes about 6,5 hours. At a renal failure it increases, the risk of cumulation of drug appears.

Indications to use:

• a diabetes mellitus of type 2 at adults;
• in a combination with insulin - at a diabetes mellitus of type 2, especially at the expressed degree of obesity which is followed by secondary resistance to insulin;
• a diabetes mellitus of type 2 at children from 10-year age - both at monotherapy, and in combination with insulin.

Route of administration and doses:

Adults: monotherapy and a combination therapy in combination with other peroral hypoglycemic means:
• The usual initial dose makes 500 mg 2-3 times a day after or during meal. Perhaps further gradual increase in a dose depending on glucose level in blood.
• The maintenance dose of drug usually makes 1500 - 2000 mg/days. For reduction of by-effects from digestive tract the daily dose should be divided into 2-3 receptions. The maximum dose makes 3000 mg/days, divided into three receptions.
• Slow increase in a dose can promote improvement of gastrointestinal portability.
• The patients accepting Metforminum in doses of 2000-3000 mg/days can be transferred to reception of Глюкофажа® 1000 mg. The maximum recommended dose makes 3000 mg a day, divided into three receptions.
In case of planning of transition from reception of other hypoglycemic means: it is necessary to stop reception of other means and to begin administration of drug of Glyukofazh® in the dose stated above. • A combination with insulin:
In blood metformin and insulin can be applied to achievement of the best control of glucose in the form of a combination therapy. The usual initial dose of the drug Глюкофаж® 500 of mg and 850 mg makes one tablet 2-3 times a day, Глюкофаж® 1000 mg - one tablet of 1 times a day while the dose of insulin is selected on the basis of results of measurement of glucose of blood.
• Children and teenagers:
at children from 10-year age of Glyukofazh® it can be applied both at monotherapy, and in combination with insulin. The usual initial dose makes 500 mg 2-3 times a day after or during meal. In 10-15 days the dose needs to be corrected on the basis of results of measurement of glucose of blood. The maximum daily dose makes 2000 mg, divided into 2-3 receptions.
• Patients of advanced age:
because of possible depression of function of kidneys the dose of Metforminum needs to be selected under regular control of indicators of function of kidneys (creatinine level in serum not less than two-four times a year).

Features of use:

If during treatment the patient had a vomiting, abdominal pains, muscular pains, the general weakness and a strong indisposition, it is necessary to stop administration of drug and to see immediately a doctor. These symptoms can be a symptom of the beginning lactoacidosis.
In 48 hours prior to and within 48 hours after carrying out a X-ray contrast research (urography, an intravenous angiography) it is necessary to stop reception of Glyukofazha®.
As metformin is removed by kidneys, before an initiation of treatment and is regular in the subsequent, it is necessary to determine creatinine levels in blood serum. Extra care needs to be shown when function of kidneys, for example, during an initial stage of anti-hypertensive therapy or therapy can be broken by diuretics, and at initial therapy of NPVP.
The patient needs to report to the doctor about emergence of a bronchopulmonary infection or infectious disease of urinogenital bodies.
During treatment it is necessary to abstain from alcohol intake.

Influence on ability to drive the car and to work with mechanisms
 Monotherapy by the drug Glyukofazh® does not cause a hypoglycemia and therefore does not influence ability to drive the car and to work with mechanisms.
However patients have to treats with care risk of emergence of a hypoglycemia at use of Metforminum in a combination with other hypoglycemic medicines (sulphonylurea derivatives, insulin, репаглинид, etc.).

Side effects:

Frequency of side effects of drug is regarded as follows:
Very frequent:> 1/10
Frequent:> 1/100, <1/10
Infrequent:> 1/1000, <1/100
Rare:> 1/10 000, <1/1000
Very rare: <1/10 000
Unknown: cannot be estimated at the available data.
Side effect is presented as decrease in the importance:
Nervous system:
Often: taste disturbance
Gastrointestinal disturbances:
Very often: nausea, vomiting, diarrhea, abdominal pains and lack of appetite. Most often they arise during an initial stage of treatment and in most cases spontaneously pass. For prevention of symptoms it is recommended to accept time metformin 2 or 3 in day in time or after meal. Slow increase in a dose can improve gastrointestinal portability.
Skin and hypodermic cellulose:
Very seldom: skin reactions such as erythema, itch, rash.
Disbolism:
Very seldom: lactoacidosis (Special instructions and preventions).
At the patients receiving a long time treatment by Metforminum the decrease in absorption of B12 vitamin which was followed by decrease in its concentration in blood serum was observed. These effects are quickly reversible at Metforminum cancellation, and are usually clinically not significant (<0,01%). Decrease in level of B12 vitamin needs to be taken into account at patients with megaloblastny anemia.
Gepato-biliarnye frustration:
There are single messages on disturbance of indicators of function of a liver or hepatitises; after Metforminum cancellation the undesirable phenomena completely disappear. The published data, post-marketing data, and also controlled clinical trials in limited children's population in an age group of 10 - 16 years show that side effects in character and weight are similar to those at adult patients.

Interaction with other medicines:

Not recommended combinations
 The concomitant use of a danazol in order to avoid hyper glycemic action of the last is not recommended. In need of treatment danazoly and after the termination of reception of the last dose adjustment of Glyukofazha® under control of level of content of glucose is required.
Alcohol intake increases risk of development of lactoacidosis during an acute drunkenness, especially in cases of starvation or observance of a low-calorie diet, and also at a liver failure. During administration of drug it is necessary to avoid alcohol intake and the medicines containing ethanol.
The combinations demanding extra care
Chlorpromazinum: at reception in high doses (100 mg a day) raises a glycemia, reducing insulin release. At treatment by neuroleptics and after the termination of reception of the last dose adjustment of Glyukofazha® under control of level of a glycemia is required.
Glucocorticosteroids (GKS) of systemic and local action reduce tolerance to glucose, raise a glycemia, sometimes causing a ketosis. At treatment of GKS, and after the termination of reception of the last, dose adjustment of Glyukofazha® under control of level of a glycemia is required.
Diuretics: the concomitant use of loopback diuretics can lead to development of lactoacidosis because of a possible functional renal failure. It is not necessary to appoint Glyukofazh® if the clearance of creatinine is lower than 60 ml/min.
Iodinated X-ray contrast means: the radiological research using iodinated X-ray contrast means can cause development of lactoacidosis in patients with a diabetes mellitus against the background of a functional renal failure. Purpose of Glyukofazha® should be cancelled in 48 hours prior to and not to renew before 2 days after X-ray inspection with use of X-ray contrast means.
The sympathomimetics appointed in the form of injections beta-2: raise a glycemia owing to stimulation beta 2 - adrenoceptors. In this case control of a glycemia is necessary. If necessary purpose of insulin is recommended. It is necessary to take into account that APF inhibitors and other anti-hypertensive medicines can reduce glucose level in blood. If necessary it is necessary to correct Metforminum dose.
At simultaneous use of Glyukofazha® with sulphonylurea derivatives, insulin, acarbose, salicylates strengthening of hypoglycemic action is possible.

Contraindications:

• hypersensitivity to Metforminum or to any of excipients;
• diabetic ketoacidosis, diabetic prekoma, coma;
• renal failure (clearance of creatinine less than 60 ml/min.);
• the acute diseases proceeding with risk of development of a renal failure: dehydration (at diarrhea, vomiting), fever, serious infectious diseases, conditions of a hypoxia (shock, sepsis, renal infections, bronchopulmonary diseases);
• clinically expressed displays of acute and chronic diseases which can lead to development of a fabric hypoxia (heart or respiratory failure, an acute myocardial infarction, etc.)
• serious surgeries and injuries (when performing insulin therapy is shown);
• abnormal liver function;
• alcoholism, acute alcoholic poisoning;
• pregnancy, breastfeeding period;
• lactoacidosis (including and in the anamnesis);
• use within not less than 2 days to and within 2 days after carrying out radio isotope or X-ray inspections with administration of iodinated contrast medium;
• observance of a hypocaloric diet (less than 1000 kal/days);
It is not recommended to use drug at persons 60 years performing hard physical activity are more senior.
Use during pregnancy and during breastfeeding
 When planning pregnancy, and also in case of approach of pregnancy against the background of Metforminum reception, drug has to be cancelled, and an insulin therapy is appointed. For mother and the newborn observation is established. As there are no data on penetration into breast milk, this drug is contraindicated when breastfeeding.
In need of use of Metforminum during breastfeeding feeding by a breast should be stopped.

Overdose:

At use of Metforminum in a dose to 85 g development of a hypoglycemia was not observed.
However in this case development of lactoacidosis was observed. Early symptoms of lactoacidosis are nausea, vomiting, diarrhea, fervescence, abdominal pains, muscle pains, breath increase, dizziness, disturbance of consciousness and development of a coma can be noted further.
Treatment: In case of symptoms of lactoacidosis, treatment by the drug Glyukofazh® needs to be stopped immediately, sick urgently to hospitalize and, having defined concentration of a lactate, to specify the diagnosis. The most effective action for removal from an organism of a lactate and Metforminum is the hemodialysis. Carry out also symptomatic treatment.

Storage conditions:

List B. To store at a temperature not above 25 °C. To store in the place, unavailable to children. Term godnosti3 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 500 mg:
On 10 tablets in the blister from PVC / aluminum foil, on 3 or 5 blisters together with the application instruction place in a cardboard pack; On 15 tablets in the blister from PVC / aluminum foil, on 2 blisters together with the application instruction place in a cardboard pack;
On 20 tablets in the blister from PVC / aluminum foil, on 3 or 5 blisters together with the application instruction place in a cardboard pack.
Tablets film coated 850 mg:
On 15 tablets in the blister from PVC / aluminum foil, on 2 blisters together with the application instruction place in a cardboard pack;
On 20 tablets in the blister from PVC / aluminum foil, on 3 or 5 blisters together with the application instruction place in a cardboard pack.
Tablets film coated 1000 mg
 On 10 tablets in the blister from PVC / aluminum foil, on 3, 5, 6 or 12 blisters together with the application instruction place in a cardboard pack;
On 15 tablets in the blister from PVC / aluminum foil, on 2, 3 or 4 blisters together with the application instruction place in a cardboard pack.