Глимекомб®

General characteristics. Structure:

Active ingredients: 500 mg of Metforminum of a hydrochloride in terms of 100% substance, 40 mg of gliclazide in terms of 100% substance.

Excipients: sorbitol, povidone, croscarmellose sodium, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. ^{Глимекомб®} represents the fixed combination of two peroral hypoglycemic means of various pharmacological groups: gliclazide and metformin. Has pancreatic and extra pancreatic effects.

Gliclazide stimulates insulin secretion with a pancreas, increases sensitivity of peripheral fabrics to insulin. Stimulates activity of desmoenzymes — a muscular glikogensintetaza. Recovers early peak of secretion of insulin, reduces a period from the meal moment prior to insulin secretion, reduces a postprandialny hyperglycemia. In addition to influence on carbohydrate metabolism, exerts impact on microcirculation, reduces adhesion and aggregation of thrombocytes, development of a mural thrombosis detains, normalizes permeability of vessels and interferes with development of microthrombosis and atherosclerosis, recovers process of a physiological pristenochny fibrinolysis, counteracts the increased reaction to adrenaline of vessels at mikroangiopatiya. Slows down development of a diabetic retinopathy at not proliferative stage; at a diabetic nephropathy against the background of prolonged use reliable decrease in a proteinuria is noted. Does not lead to increase in body weight as makes preferential impact on early peak of an insulinosekretion and does not cause a giperinsulinemiya; promotes decrease in body weight at corpulent patients at observance of the corresponding diet.

Metforminum concerns to group of guanyl guanidines. Reduces concentration of glucose in blood by oppression of a gluconeogenesis in a liver, reduction of absorption of glucose from digestive tract and increase in its utilization in fabrics. Reduces concentration in blood serum of the triglycerides, cholesterol and lipoproteins of low density (defined on an empty stomach) and does not change concentration of lipoproteins of other density. Promotes stabilization or decrease in body weight. At absence in insulin blood the therapeutic effect is not shown. Does not cause hypoglycemic reactions. Improves fibrinolitic properties of blood due to suppression of inhibitor of the activator of plasminogen (plasminogen) of fabric type.

Pharmacokinetics. Gliclazide. Absorption — high. After oral administration of 40 mg the maximum concentration in a blood plasma is reached in 2 - 3 h and makes 2 - 3 mkg/ml. Communication with proteins of plasma — 85 - 97%. An elimination half-life — 8 - 20 h. It is metabolized in a liver.

It is removed preferential in the form of metabolites by kidneys — 70%, through intestines — 12%.

At elderly people of clinically significant changes of pharmacokinetic parameters it is not noted.

Metforminum. Absorption — 48 - 52%. It is quickly soaked up in digestive tract. Absolute bioavailability (on an empty stomach) makes 50 - 60%, reception with food reduces the maximum concentration by 40% and slows down its achievement for 35 min. Concentration in a blood plasma is reached in 1,81 - 2,69 h and does not exceed 1 mkg/ml. Communication with proteins of plasma - insignificant, it is capable to collect in erythrocytes. An elimination half-life — 6,2 h. It is removed by kidneys, it is preferential in not changed look (glomerular filtering and canalicular secretion) and through intestines (to 30%).

Indications to use:

• Diabetes mellitus 2 types at inefficiency of a dietotherapy, physical exercises and the previous therapy by metformin or gliclazide.
• Substitution of the previous therapy by two drugs (metformin and gliclazide) at patients with a diabetes mellitus 2 types with the stable and well controlled level of glucose of blood.

Route of administration and doses:

Drug is used inside, in time or right after food. The dose of drug is defined by the doctor individually for each patient depending on blood glucose level.

Usually initial dose makes 1 - 3 tablets a day with gradual selection of a dose before achievement of permanent compensation of a disease.

Usually drug is accepted by 2 times a day (yrpom and in the evening). The maximum daily dose makes 5 tablets.

Features of use:

Treatment ^{by the drug Glimekomb®} is carried out only in combination with a low-calorie diet with the small content of carbohydrates. It is regularly necessary to control the content of glucose in blood on an empty stomach and after meal, especially in the first days of treatment by drug.

^{Глимекомб®} it can be appointed only to the patients receiving the regular food which is surely including a breakfast and providing sufficient intake of carbohydrates. At purpose of drug it is necessary to consider that owing to reception of derivatives of sulphonylurea the hypoglycemia, and in certain cases — in the severe and long form demanding hospitalization and administration of glucose within several days can develop. The hypoglycemia develops at a low-calorie diet, after long or vigorous physical exercises, after alcohol intake or during reception of several hypoglycemic drugs at the same time more often.

In order to avoid development of a hypoglycemia careful and individual selection of doses, and also representation of the complete information to the patient about the offered treatment is necessary.

At a physical and emotional overstrain, at change of a diet dose adjustment of Glimekomba is necessary.

Are especially sensitive to effect of hypoglycemic drugs: elderly people; the patients who are not receiving the balanced food with the general weakened state; the patients suffering from pituitary and adrenal insufficiency. Beta adrenoblockers, a clonidine, Reserpinum, гуанетидин can mask clinical manifestations of a hypoglycemia.

It is necessary to warn patients about the increased risk of emergence of a hypoglycemia in cases of reception of ethanol, NPVP, at starvation.

Big surgical interventions and injuries, extensive burns, infectious diseases with a feverish syndrome can demand cancellation of peroral hypoglycemic medicines and purpose of an insulin therapy. 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. Development of lactoacidosis demands the treatment termination.
For 48 h to surgical intervention or intravenous administration of iodinated X-ray contrast means reception ^{of Glimekomba®} should be stopped; treatment is recommended to be resumed in 48 h.

Against the background of therapy ^{by the drug Glimekomb®} the patient needs to refuse alcohol intake and/or the drugs and foodstuff containing ethanol.

During treatment it is necessary to be careful during the driving of motor transport and occupation other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Use during pregnancy and breastfeeding. During pregnancy use ^{of the drug Glimekomb®} is contraindicated. When planning pregnancy, and also in case of approach of pregnancy during reception ^{of Glimekomba®}, drug has to be an insulin therapy is cancelled and is appointed.

^{Глимекомб®} it is contraindicated when breastfeeding as drug is capable to get into breast milk. In this case it is necessary to pass to an insulin therapy or to stop feeding by a breast.

Side effects:

From a metabolism: at disturbance of the mode of dosing and an inadequate diet — a hypoglycemia (a headache, feeling of fatigue, feeling of hunger, the increased sweating, sharp weakness, heartbeat, dizziness, a lack of coordination of movements, temporary neurologic frustration; when progressing a hypoglycemia loss by the patient of self-checking and consciousness is possible); in some cases — lactoacidosis (weakness, a mialgiya, respiratory disturbances, drowsiness, an abdominal pain, a hypothermia, a lowering of arterial pressure, a reflex bradyarrhythmia).

From the alimentary system: dyspepsia (nausea, diarrhea, heavy feeling in epigastriums, "metal" smack in a mouth), a loss of appetite — expressiveness decreases at administration of drug during food; seldom — damage of a liver (hepatitis, cholestatic jaundice — demands drug withdrawals, increase in activity of "hepatic" transaminases, an alkaline phosphatase).

From bodies of a hemopoiesis: seldom — oppression of a marrowy hemopoiesis (anemia, thrombocytopenia, a leukopenia).

Allergic reactions: itch, urticaria, makulopapulezny rash.

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

Others: vision disorder.

Cumulative side effects of derivatives of sulphonylurea: erythropenia, agranulocytosis, hemolitic anemia, pancytopenia, allergic vasculitis; zhizneugrozhayushchy liver failure.

Interaction with other medicines:

Inhibitors of an angiotensin-converting enzyme (captopril, enalapril), blockers _{of H2-histamine} receptors (Cimetidinum), antifungal medicines (Miconazolum, флуконазол), non-steroidal anti-inflammatory drugs (NPVP) (phenylbutazone, азапропазон, оксифенбутазон), fibrata (Clofibratum, безафибрат), antitubercular (Etioniamidum), salicylates, anticoagulants of a coumarinic row, anabolic steroids, beta adrenoblockers, monoaminooxidase inhibitors, streptocides of long action, cyclophosphamide, chloramphenicol, фенфлурамин, fluoxetine, гуанетидин, пентоксифиллин, tetracycline, theophylline, blockers of canalicular secretion, Reserpinum, Bromocriptinum, Disopyramidum, a pyridoxine, other hypoglycemic drugs (acarbose, guanyl guanidines, insulin, etc.), Allopyrinolum, Oxytetracyclinum strengthen hypoglycemic effect of drug.

Barbiturates, glucocorticosteroids, adrenomimetik (Epinephrinum, clonidine), antiepileptic drugs (Phenytoinum), blockers of "slow" calcium channels, inhibitors of a karboangidraza (acetazoleamide), thiazide diuretics, Chlortalidonum, furosemide, Triamterenum, asparaginase, Baclofenum, даназол, diazoxide, an isoniazid, morphine, Ritodrinum, salbutamol, тербуталин, a glucagon, rifampicin, hormones of a thyroid gland, lithium salt, in high doses — niacin, Chlorpromazinum, oral contraceptives and estrogen weaken effect.

Increases risk of development of ventricular premature ventricular contraction against the background of cardiac glycosides. The medicines oppressing a marrowy hemopoiesis increase risk of a miyelosupressiya.

Ethanol strengthens probability of development of lactoacidosis.

Metforminum reduces the maximum concentration in blood (Cmax) and T1/2 of furosemide by 31 and 42,3% respectively.

Furosemide increases Metforminum Cmax by 22%.

Nifedipine increases absorption, Cmax, slows down Metforminum removal.

Cationic medicines (amiloride, digoxin, morphine, procaineamide, quinidine, quinine, ranitidine, Triamterenum and Vancomycinum) cosecreting in tubules compete for tubular transport systems and at long therapy can increase Metforminum Cmax by 60%.

Contraindications:

• Hypersensitivity to metformin, gliclazide or other derivatives of sulphonylurea, and also to excipients;
• diabetes mellitus of 1 type;
• diabetic ketoacidosis, diabetic prekoma, diabetic coma;
• hypoglycemia;
• heavy renal failures;
• acute states which can lead to change of function of kidneys: dehydration, heavy infection, shock;
• the acute or chronic diseases which are followed by a hypoxia of fabrics: heart or respiratory failure, recent myocardial infarction, shock;
• liver failure;
• porphyria;
• pregnancy, breastfeeding period;
• concomitant use of Miconazolum;
• the infectious diseases, big surgical interventions, injuries, extensive burns and other states demanding performing insulin therapy;
• alcoholism, acute drunkenness;
• lactoacidosis (including in the anamnesis);
• use during not less than 48 h to and during 48 h after carrying out radio isotope or X-ray inspections with administration of iodinated contrast medium;
• observance of a hypocaloric diet (less than 1000 кал / days).

It is not recommended to use drug at persons 60 years performing hard physical activity that is connected with the increased risk of development of lactoacidosis at them are more senior.

With care. A feverish syndrome, adrenal insufficiency, hypofunction of a front share of a hypophysis, a disease of a thyroid gland with disturbance of its function.

Overdose:

The overdose or existence of risk factors can provoke development of lactoacidosis as Metforminum is a part of drug. At emergence of symptoms of lactoacidosis it is necessary to stop administration of drug. Lactoacidosis is the state demanding emergency medical service; treatment of lactoacidosis has to be carried out in a hospital.

The most effective method of treatment is the hemodialysis.

The overdose can also lead to development of a hypoglycemia because of presence at composition of drug of gliclazide. At a hypoglycemia easy either moderately severe glucose (dextrose) or solution of sugar is accepted inside. In case of a heavy hypoglycemia (loss of consciousness) solution of a dextrose (glucose) or a glucagon intravenously, intramusculary, subcutaneously enter intravenously 40%. After consciousness recovery the patient needs to give food, carbohydrate-rich, in order to avoid repeated razviriya to a hypoglycemia.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. Not to apply after a period of validity. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets of 40 mg + 500 mg. On 30 tablets in a bottle for medicines from plastic. On 10 or 20 tablets in a blister strip packaging. Each bottle or 6 blister strip packagings on 10 tablets, or 5 blister strip packagings on 20 tablets together with the application instruction in a pack from a cardboard.