Глюкофаж® Long

General characteristics. Structure:

Active agent: Metforminum a hydrochloride - 750 mg
Excipients: a karmelloza of sodium - 37,5 mg; gipromelloza of 2208 - 294,24 mg; magnesium stearate - 5,3 mg.

Description: Kapsulovidny biconvex tablets of white or almost white color, with an engraving "750" on one party and "Merck" - on another.

Pharmacological properties:

Pharmacodynamics. 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.
Metforminum stimulates synthesis of a glycogen, influencing a glikogensintaza. Increases the transport capacity of all types of membrane carriers of glucose.

Pharmacokinetics. Absorption
 After oral administration of drug in the form of a tablet of the prolonged action, absorption of Metforminum is slowed down 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 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.
At reception of tablets of the prolonged action on an empty stomach, AUC decreases by 30%, however the maximum concentration (Cmax) and TCmax are left without changes. Absorption of Metforminum from tablets of the prolonged action 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. Cmax in blood below Cmax in plasma, is also reached approximately through the same time. The average volume of distribution (Vd) 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:

Diabetes mellitus 2 types at adults (especially at patients with obesity) at inefficiency of a dietotherapy and exercise stresses:
• as monotherapy;
• in combination with other peroral hypoglycemic means or with insulin.

Route of administration and doses:

The drug Glyukofazh® Longum in the form of tablets of the prolonged action of 750 mg is accepted inside. Tablets are swallowed entirely, without chewing, washing down with a small amount of liquid, in time or after a dinner (once a day).
Monotherapy and combination therapy in combination with other hypoglycemic means
• The usual initial dose makes one tablet once a day.
• In 10-15 days of the carried-out treatment the dose needs to be corrected on the basis of results of measurement of concentration of glucose in blood. Slow increase in a dose promotes decrease in side effects from digestive tract. The recommended drug Glyukofazh® dose Longum makes 2 tablets on 750 mg once a day. If at reception of the recommended dose it is not possible to reach adequate control of a glycemia, increase in a dose to maximum - 3 tablets on 750 mg of the drug Glyukofazh® Longum is possible once a day.
• If adequate control of a glycemia is not reached at reception of 3 tablets on 750 mg of the drug Glyukofazh® Longum once a day, transition to Metforminum drug with usual release of active ingredient with the maximum daily dose of 3000 mg is possible.
• For the patients who are already receiving treatment by Metforminum tablets, the initial dose of the drug Glyukofazh® of Long has to be equivalent to a daily dose of tablets with usual release. Transition to Long's Glyukofazh® is not recommended to the patients accepting Metforminum in the form of tablets with usual release of active ingredient in the dose exceeding 2000 mg.
• In case of planning of transition from other hypoglycemic means: it is necessary to stop reception of other means and to begin administration of drug of Glyukofazh® of Long in the dose stated above.
Combination with insulin
 In blood metformin and insulin can be applied to achievement of the best control of concentration of glucose in the form of a combination therapy. The usual initial dose of the drug Glyukofazh® Longum makes one tablet of 750 mg once a day during a dinner while the dose of insulin is selected on the basis of results of measurement of content of glucose in blood.
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 should not be used at children and teenagers up to 18 years due to the lack of data on use.
Treatment duration
 Глюкофаж® Long should be accepted daily, without interruption. In case of the treatment termination the patient has to report about it to the doctor.

Features of use:

Lactoacidosis is rare, but serious (high mortality in the absence of urgent treatment) a complication which can arise because of Metforminum cumulation. Lactoacidosis cases at reception of 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 dekompensirovanny diabetes mellitus, ketosis, long starvation, alcoholism, 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. Lactoacidosis is characterized by an atsidotichesky asthma, an abdominal pain and a hypothermia with the subsequent coma. Diagnostic laboratory indicators are decrease рН blood (less than 7,25), the maintenance of a lactate in a blood plasma over 5 mmol/l, the raised anion intervals and the relation lactate/pyruvate. At suspicion on a metabolic acidosis 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 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 anti-hypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.
It is regularly necessary to carry out standard laboratory analyses for control of a diabetes mellitus.
It is necessary to warn the patient that inactive components of the drug Glyukofazh® Longum can be allocated in not changed look through intestines that does not influence therapeutic activity of drug.

Influence on ability to manage motor transport and to work with mechanisms
 Monotherapy by the drug Glyukofazh® Longum does not cause a hypoglycemia therefore does not influence ability to manage vehicles 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).
Gastrointestinal disturbances:
Very often: nausea, vomiting, diarrhea, abdominal pains and lack of appetite. Emergence of these side effects is most probable during an initial stage of treatment and in most cases they spontaneously pass. For prevention of symptoms it is recommended to accept Metforminum 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, urticaria.
Disbolism:
Very seldom: lactoacidosis (See. "Special instructions").
At long reception of Metforminum decrease in absorption of B12 vitamin can be observed. At detection of megaloblastny anemia it is necessary to consider a possibility of such etiology.
Gepato-biliarnye frustration:
There are single messages on disturbance of indicators of function of a liver or hepatitis; after Metforminum cancellation the undesirable phenomena completely disappear.

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. Treatment by the drug Glyukofazh® Longum needs to be cancelled depending on function of kidneys in 48 hours prior to or for the period of X-ray inspection with use of iodinated X-ray contrast means and not to renew before 48 hours later provided that during inspection renal function was recognized as normal.
Not recommended combinations
Alcohol: at an acute drunkenness the risk of development of lactoacidosis, especially in a case increases:
• 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 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 drug Glyukofazh® dose adjustment Longum 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 dose adjustment of drug under control 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 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 beta2-adrenomimetik appointed in the form of injections: raise a glycemia owing to stimulation of beta2-adrenoceptors. 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 concentration of glucose 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 development of a hypoglycemia is possible.
Nifedipine increases absorption and Cmax of Metforminum.
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 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: dehydration (at diarrhea, vomiting), serious infectious diseases, shock;
• clinically expressed displays of acute or 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 48 hours to and within 48 hours 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 kcal/days);
• children's age up to 18 years.
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 researches on penetration of Metforminum into breast milk in public were not conducted, this drug is contraindicated when breastfeeding. In need of drug Glyukofazh® use Longum 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 1 development of lactoacidosis was observed. The considerable overdose or the interfaced risk factors can lead to development of lactoacidosis (see. "Special instructions").
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, 750 mg.
On 15 tablets in the blister from the Pvkhualyuminiyevy foil or PVC/PVDH / aluminum foil, on 2 or 4 blisters together with the application instruction place in a cardboard pack.
The M symbol for protection against falsification is applied on the blister and a cardboard pack.