Глюкофаж® Long

General characteristics. Structure:

Active agent: Metforminum a hydrochloride - 500 mg
Excipients: karmelloza of sodium, gipromelloz 2910, gipromelloza 2208, cellulose microcrystallic, magnesium stearate.

Description

Kapsulovidny biconvex tablets of white or almost white color, with an engraving "500" on one party.

Pharmacological properties:

Metformin – the guanyl guanidine with hypoglycemic action reducing both the basal, and postprandialny content of glucose in a blood plasma. Does not stimulate secretion of insulin and in this regard does not cause a hypoglycemia. Increases sensitivity of peripheral receptors to insulin and glucose utilization by cells. Reduces production of glucose liver at the expense of inhibition of a gluconeogenesis and a glycogenolysis. Absorption of glucose in intestines detains.

Pharmacokinetics. Absorption
After oral administration of a dose in the form of a tablet of the prolonged action, Metforminum absorption in a slowed-up way in comparison with a tablet with usual release of Metforminum. Time of achievement of the maximum concentration (TCmax) makes 7 hours. At the same time TCmax for a tablet with usual release makes 2,5 hours.

After a single dose in 2000 mg of Metforminum in the form of tablets of the prolonged action the area under a curve "concentration – time" is similar (AUC) the observed ambassador of reception of 1000 mg of Metforminum in the form of tablets with usual release two times a day. Fluctuations of the maximum concentration of Metforminum (Cmax) and AUC at certain patients in case of reception of Metforminum in the form of tablets of the prolonged action are comparable with the same indicators, as well as in case of reception of tablets with a usual profile of release. Absorption of Metforminum from tablets of the prolonged release does not change depending on meal. Cumulation at multiple dose to 2000 mg of Metforminum in the form of tablets of the prolonged action is not observed.

Distribution
 Communication with proteins of plasma is insignificant. Metforminum partially contacts erythrocytes. Cmax in blood below Cmax in plasma, is also reached approximately through the same time. At usual therapeutic doses of cumulation of Metforminum in plasma it is not observed, except for cases of a renal failure. The average volume of distribution fluctuates in the range of 63-276 l.

Metabolism
 Metforminum does not participate in a metabolism, and as communication with proteins of plasma is insignificant, is metabolized in an untied form. Metabolites at the person are not revealed. Metformin is removed in not changed look by kidneys.

Removal
 The renal clearance of Metforminum makes> 400 ml/min. that indicates that metformin is removed due to glomerular filtering and canalicular secretion. After oral administration the elimination half-life makes about 6,5 hours.

At an impaired renal function the clearance of Metforminum decreases in proportion to clearance of creatinine, the elimination half-life increases that can lead to increase in concentration of Metforminum in plasma.

Indications to use:

Treatment of a diabetes mellitus 2 types at adults at inefficiency of a dietotherapy (especially at the patients having obesity) as monotherapy, or in combination with other peroral hypoglycemic means, or with insulin.

Route of administration and doses:

The drug Glyukofazh® Longum of the prolonged action is appointed inside. Tablets are swallowed, without chewing, during a dinner (once a day) or during a breakfast and a dinner (2 times a day). A pill should be taken only during food.

The dose of drug is defined, proceeding from the content of glucose in a blood plasma.

Monotherapy and combination therapy in combination with other hypoglycemic means

Usual initial dose

Глюкофаж® Long of the prolonged action of 500 mg: 1 tablet once a day during a dinner.

Upon transition from the drug Glyukofazh® with usual release of active component the initial dose of the drug Glyukofazh® of Long of the prolonged action has to be to an equal daily dose of the drug Glyukofazh® with usual release of active component.

Titration of a dose
 Depending on the content of glucose in a blood plasma, every 10-15 days the dose is slowly increased by 500 mg to the maximum daily dose.

Maximum daily dose
 Глюкофаж® Long of the prolonged action of 500 mg: 4 tablets once a day during a dinner.

If control of content of glucose is not reached at the maximum daily dose accepted once a day, then it is possible to consider the possibility of division of this dose into several receptions in day according to the following scheme:
Глюкофаж® Long of the prolonged action of 500 mg: 2 tablets during a breakfast and 2 tablets during a dinner.

Combination with insulin
 At drug Glyukofazh® use Longum of the prolonged action together with insulin the usual initial dose of drug makes 1 tablet once a day, and the dose of insulin is selected, proceeding from results of measurement of content of glucose in a blood plasma.

Treatment duration
 Глюкофаж® Long of the prolonged action should be accepted daily, without interruption. In case of the treatment termination the patient has to report about it to the doctor.

Admission of a dose
 In case of the admission of the next dose the following dose should be accepted in usual time. It is impossible to double a drug dose.

Elderly patients and patients with reduced function of kidneys
 To elderly patients and patients with reduced function of kidneys the dose is adjusted on the basis of assessment of renal function which it is necessary to carry out regularly not less than 2 times a year.

Children
 The drug Glyukofazh® Longum of the prolonged action should not be used at children and teenagers up to 18 years due to the lack of data on use.

Features of use:

Lactoacidosis is extremely rare, but serious (high mortality in the absence of urgent treatment) a complication which can arise because of Metforminum cumulation. Lactoacidosis cases at the patients receiving Metforminum arose generally at patients with a diabetes mellitus with the expressed renal failure.

It is necessary to consider also other interfaced risk factors, such as badly controlled diabetes, ketosis, long starvation, alcohol overconsumption, liver failure and any state connected with the expressed hypoxia. It can help to reduce the frequency of cases of developing of lactoacidosis.

It is necessary to consider risk of development of lactoacidosis at emergence of nonspecific signs such as the muscular pains, spasms which are followed by dispepsichesky frustration, an abdominal pain, the general weakness and a strong indisposition. In this case it is necessary to stop administration of drug and to see immediately a doctor.

Use of Metforminum has to be stopped in 48 hours prior to carrying out planned surgeries and can be continued not earlier than in 48 hours later provided that during inspection renal function was recognized as normal.

As metformin is removed by kidneys, before an initiation of treatment, and is regular in the subsequent, it is necessary to determine the content and/or clearance of creatinine in serum: at least once a year at patients with normal function of kidneys, and 2-4 times a year at elderly patients, and also at patients with clearance of creatinine on the lower bound of norm. The drug Glyukofazh® Longum in the form of tablets of the prolonged action is recommended to begin therapy after assessment of function of kidneys. At decrease in clearance of creatinine it is necessary to control function of kidneys at least 2 - 4 times a year.

It is necessary to show extra care at possible disturbance of functions of kidneys at elderly patients, at simultaneous use of hypotensive drugs, diuretics or NPVP. The patient has to report to the doctor about emergence of a bronchopulmonary infection or infectious disease of urinogenital bodies.

It is regularly necessary to carry out standard laboratory analyses for control of a diabetes mellitus.

During treatment it is necessary to abstain from alcohol intake.

It is necessary to warn the patient that inactive components of the drug Glyukofazh® Longum in the form of tablets of the prolonged action can be allocated in not changed look through intestines that Longum does not influence therapeutic activity of the drug Glyukofazh®.

Influence on ability to drive the car and to work with mechanisms
 Monotherapy by the drug Glyukofazh® Longum of the prolonged action does not cause a hypoglycemia and therefore does not influence ability to drive the car and to work with mechanisms.

Nevertheless, it is necessary to warn patients about risk of a hypoglycemia at use of Metforminum in combination with other hypoglycemic drugs (sulphonylurea derivatives, insulin, репаглинид).

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
• Single: cannot be estimated at the available data.

Side effect is presented as decrease in the importance:

Nervous system:
Often: taste disturbance (metal smack in a mouth - 3%).

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 Metforminum in time or after meal, having divided a daily dose into 2 receptions a day. Slow increase in a dose can improve gastrointestinal portability. At long preservation of symptoms it is necessary to stop administration of drug and to see behind consultation a doctor.

Skin and hypodermic cellulose:
Very seldom: skin reactions such as erythema, itch, urticaria.

Disbolism:
Very seldom: lactoacidosis (See. "Special instructions").
At the patients receiving treatment by Metforminum a long time the decrease in absorption of B12 vitamin which is followed by decrease in its concentration in blood serum can be observed. At detection of megaloblastny anemia it is necessary to consider a possibility of such etiology. Early symptoms of lactoacidosis are nausea, vomiting, diarrhea, decrease in body temperature, an abdominal pain, muscle pain, breath increase, dizziness, disturbance of consciousness and development of a coma can be noted further.

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.
If dispeptic symptoms do not disappear, treatment by Metforminum should be stopped.

Interaction with other medicines:

Contraindicated combinations
Iodinated X-ray contrast means: against the background of a functional renal failure the radiological research using iodinated X-ray contrast means can cause development of lactoacidosis in patients with a diabetes mellitus. Purpose of the drug Glyukofazh® Longum should be cancelled in 48 hours prior to and not to renew before 2 days after X-ray inspection with use of iodinated X-ray contrast means provided that during inspection renal function was recognized as normal.

Not recommended combinations
 Alcohol intake increases risk of development of lactoacidosis during an acute drunkenness, especially in a case:
• hyponutrient, observance of a low-calorie diet
• liver failure.
During administration of drug it is necessary to avoid the alcohol intake and medicines containing ethanol.

The combinations demanding extra care
Danazol: 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 Glyukofazh® of Long under control of content of glucose is required.

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 drug Glyukofazh® dose adjustment Longum 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, drug Glyukofazh® dose adjustment Longum 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 Long's Glyukofazh® if the clearance of creatinine is lower than 60 ml/min.

The sympathomimetics appointed in the form of injections beta-2: raise a glycemia owing to stimulation beta 2 - receptors. In this case control of a glycemia is necessary. If necessary purpose of insulin is recommended.

At simultaneous use of above-mentioned medicines more frequent control of content of glucose in blood, especially in an initiation of treatment can be required. If necessary the dose of Metforminum can be corrected in the course of treatment and after its termination.

Inhibitors of an angiotensin-converting enzyme and other anti-hypertensive medicines can reduce glucose level in blood. If necessary it is necessary to correct Metforminum dose.

At simultaneous use of the drug Glyukofazh® Longum with sulphonylurea derivatives, insulin, acarbose, salicylates strengthening of hypoglycemic action is possible.

Nifedipine increases absorption and Cmax.

Cationic medicines (amiloride, digoxin, morphine, procaineamide, quinidine, quinine, ranitidine, Triamterenum, Trimethoprimum and Vancomycinum) cosecreting in renal tubules compete for canalicular transport systems.

Contraindications:

• Hypersensitivity to Metforminum to a hydrochloride or to any excipient;
• diabetic ketoacidosis, diabetic prekoma, coma;
• renal failure or renal failure (clearance of creatinine less than 60 ml/min.);
• the acute states proceeding with risk of development of renal failures: a degidratation (at diarrhea, vomiting), fever, serious infectious diseases,
hypoxia sostoyaniya (shock, sepsis, renal infections, bronchopulmonary diseases);

• clinically expressed displays of acute and chronic diseases which can lead to development of a fabric hypoxia (including, heart or respiratory failure, an acute myocardial infarction);
• extensive surgeries and injuries when performing insulin therapy is shown (see the section "Special Instructions");
• liver failure, 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 (see the section "Interaction with Other Medicines");
• observance of a hypocaloric diet (less than 1000 kal/days).

With care

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.

Use during pregnancy and during breastfeeding

When planning pregnancy, and also in case of approach of pregnancy against the background of administration of drug of Glyukofazh® of Long, drug has to be cancelled, and an insulin therapy is appointed. The patient has to inform the doctor on approach of pregnancy against the background of administration of drug of Glyukofazh® of Long. As there are no data on penetration of Metforminum into breast milk, this drug is contraindicated when breastfeeding.

In need of drug Glyukofazh® use Longum of the prolonged action in the period of a lactation, breastfeeding it is necessary to stop.

Overdose:

At use of Metforminum in a dose of 85 g (by 42,5 times exceeding the maximum daily dose) development of a hypoglycemia was not observed. However in this case development of lactoacidosis was observed.

Treatment: In case of symptoms of lactoacidosis treatment by drug needs to be stopped immediately, urgently to hospitalize the patient 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 of the prolonged action of 500 mg.
On 15 tablets in the blister from PVC / aluminum foil, on 2 or 4 blisters together with the application instruction place in a cardboard pack.