Glucophage Long tablets 500mg, No. 60

Diabetes mellitus type 2 in adults (especially in obese patients) with ineffective diet and exercise:

- as monotherapy;

- in combination with other oral hypoglycemic agents or with insulin.

Inside. The tablets are swallowed whole, without chewing, with a small amount of liquid, 1 time per day during dinner. The dose of the drug Glucophage Long in the form of prolonged-release tablets is selected by the doctor individually for each patient based on the results of measuring the concentration of glucose in the blood.

Monotherapy and combination therapy in combination with other hypoglycemic agents.

For patients not taking metformin, the recommended initial dose of Glucophage Long is 500 mg or 750 mg once a day with dinner.

Depending on the concentration of glucose in the blood plasma, a slow increase in the dose (by 500 mg) is possible every 10-15 days until the maximum daily dose (2000 mg) is reached. A slow increase in dose helps to reduce side effects from the gastrointestinal tract.

The recommended dose of Glucophage Long is 2 tablets. 750 mg once a day. If, when taking the recommended dose, it is not possible to achieve adequate glycemic control, it is possible to increase the dose to the maximum - Table 3. 750 mg of the drug Glucophage Long 1 time per day.

For patients already receiving metformin treatment, the initial dose of Glucophage Long should be equivalent to the daily dose of conventional-release tablets.

Patients taking metformin in the form of tablets with a conventional release of the active ingredient in a dose exceeding 2000 mg are not recommended to switch to Glucophage Long.

If you plan to switch from another hypoglycemic agent, you must stop taking the other agent and start taking Glucophage Long at the dose indicated above.

Combination with insulin. Metformin and insulin can be used in combination therapy to achieve better blood glucose control. The usual starting dose of Glucophage Long is one tablet of 500 mg or 750 mg once a day during dinner, while the dose of insulin is selected based on the results of measuring the concentration of glucose in the blood.

Daily dose. The maximum recommended dose of GlucophageЃ Long is 4 tablets. 500 mg (2000 mg / day) or 3 tables. 750 mg per day (2250 mg). If, when taking the maximum recommended dose 1 time per day during dinner, it is not possible to achieve adequate glycemic control, then the maximum dose can be divided into two doses: Table 2. 500 mg during breakfast and 2 tablets of 500 mg during dinner.

If adequate glycemic control is not achieved when taking 2000 mg of the drug Glucophage Long, extended-release tablets, it is possible to switch to metformin with the usual release of the active ingredient (for example, Glucophage, film-coated tablets) with a maximum daily dose of 3000 mg.

Patients with renal impairment. Metformin can be used in patients with moderate renal insufficiency (Cl creatinine 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis. The starting dose is 500 mg or 750 mg once daily. The maximum dose is 1000 mg / day. Renal function should be closely monitored every 3Ц6 months.

If Cl creatinine is below 45 ml / min, the drug should be discontinued immediately.

Elderly patients. Due to a possible decrease in renal function, the dose of metformin is adjusted based on an assessment of renal function, which must be carried out regularly, at least 2 times a year.

The duration of the course of treatment. GlucophageЃ Long should be taken daily without interruption. In case of termination of treatment, the patient must inform the doctor about it.

Skipping a dose. If the next dose is missed, the patient should take the next dose at the usual time. Do not take a double dose of Glucophage Long.

Extended release tablets

1 tablet contains active substance: metformin hydrochloride 500 mg

excipients: sodium carmellose - 50 mg; hypromellose 2910 - 10 mg; hypromellose 2208 - 358 mg; MCC - 102 mg; magnesium stearate - 3.5 mg

Extended release tablets

1 tablet contains active substance: metformin hydrochloride 750 mg

excipients: sodium carmellose - 37.5 mg; hypromellose 2208 - 294.24 mg; magnesium stearate - 5.3 mg

Extended release tablets

1 tab. metformin hydrochloride 1000 mg

excipients: sodium carmellose - 50 mg, hypromellose 2208 - 392.3 mg, magnesium stearate - 7 mg.

• Hypersensitivity to metformin or any excipient;

• diabetic ketoacidosis, diabetic precoma, coma;

• renal failure or impaired renal function (Cl creatinine <45 ml / min);

• acute conditions with a risk of developing impaired renal function: dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (for example, respiratory tract infections, urinary tract infections), shock;

• clinically pronounced manifestations of acute or chronic diseases that can lead to the development of tissue hypoxia (including acute heart failure, chronic heart failure with unstable hemodynamic parameters, respiratory failure, acute myocardial infarction);

• extensive surgery and trauma, when insulin therapy is indicated (see 'Special instructions');

• liver failure, impaired liver function;

• chronic alcoholism, acute alcohol poisoning;

• pregnancy;

• lactic acidosis (including history);

• use for less than 48 hours before and within 48 hours after carrying out radioisotope or X-ray studies with the introduction of an iodine-containing contrast agent (eg, intravenous urography, angiography) (see 'Interaction');

• adherence to a hypocaloric diet (<1000 cal / day);

• children under 18 years of age, due to the lack of data on the use.

With caution: in patients over 60 years of age, performing heavy physical work, which is associated with an increased risk of developing lactic acidosis, in patients with renal insufficiency (Cl creatinine 45-59 ml / min), during breastfeeding.

pharmachologic effect

Metformin is a hypoglycemic biguanide that lowers both basal and postprandial plasma glucose levels. Does not stimulate insulin secretion and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral receptors to insulin and glucose utilization by cells. Reduces the production of glucose by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays the absorption of glucose in the intestine. Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters. While taking metformin, the patient's body weight either remains stable or decreases moderately. Metformin has a beneficial effect on lipid metabolism: it reduces the content of total cholesterol, LDL and triglycerides.

Pharmacokinetics

Suction

The average time to reach Cmax of metformin (1214 ng / ml) in blood plasma (TCmax) is 5 hours (in the range of 4-10 hours) after a single oral administration of 1 tablet of Glucophage Long in the dosage form of a 1000 mg extended-release tablet. In the equilibrium state, which is identical to the equilibrium state of metformin with conventional release, Cmax and AUC do not increase proportionally to the dose taken. After a single oral administration of metformin in the form of tablets with prolonged release at a dose of 2000 mg, the AUC is similar to that observed after taking metformin in the form of tablets with a conventional release at a dose of 1000 mg 2 times / day. The intra-individual variability in Cmax and AUC after administration of metformin in the form of sustained-release tablets is similar to that observed after administration of conventional-release tablets.When metformin is taken in the form of extended-release tablets at a dose of 1000 mg after a meal, the AUC increases by 77% (Cmax and T—max increase by about 1 hour). The absorption of metformin from sustained-release tablets does not change depending on the composition of the food taken. Cumulation is not observed with repeated administration of metformin in the form of extended-release tablets at a dose of up to 2000 mg.

Distribution

The connection with plasma proteins is negligible. Cmax in blood is lower than Cmax in plasma and is reached after about the same time. Average Vd ranges from 63-276 liters. Metabolism No metabolites have been found in humans.

Withdrawal

Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is> 400 ml / min, indicating that metformin is excreted by glomerular filtration and tubular secretion. After oral administration, T1 / 2 is about 6.5 hours. With impaired renal function, the clearance of metformin decreases in proportion to the CC, T1 / 2 increases, which can lead to an increase in the concentration of metformin in plasma.

Side effect

Metabolic and nutritional disorders Very rare - lactic acidosis. With long-term use of metformin, there may be a decrease in the absorption of vitamin B12. When detecting megaloblastic anemia, it is necessary to take into account the possibility of such an etiology. Nervous system disorders Often - taste disturbance (metallic taste in the mouth). Disorders from the gastrointestinal tract Very often - nausea, vomiting, diarrhea, abdominal pain and lack of appetite. Most often they occur during the initial period of treatment and in most cases disappear spontaneously. It is recommended to take metformin with or after meals to prevent symptoms. Slowly increasing the dose may improve gastrointestinal tolerance. Violations of the liver and biliary tract Very rarely - impaired liver function and hepatitis;after the abolition of metformin, these undesirable effects completely disappear. Skin and subcutaneous tissue disorders Very rarely - skin reactions such as erythema (redness of the skin), itching, urticaria. If any of the side effects indicated in the instructions are aggravated, or other side effects not indicated in the instructions are noted, the patient should be informed about this by the doctor.

Application during pregnancy and lactation

Decompensated diabetes mellitus in pregnancy is associated with an increased risk of birth defects and perinatal mortality. Limited evidence suggests that the use of metformin in pregnant women does not increase the risk of developing birth defects in children. When planning pregnancy, as well as in case of pregnancy on the background of the use of metformin, the drug should be canceled and insulin therapy should be prescribed. Maintain blood glucose levels as close to normal as possible to reduce the risk of fetal malformations. Metformin is excreted in breast milk. Side effects in newborns with breastfeeding while taking metformin were not observed. However, due to the limited amount of data, the use of the drug during breastfeeding is not recommended.The decision to stop breastfeeding should be made in light of the benefits of breastfeeding and the potential risk of side effects in the baby.

Application for violations of liver function

Contraindication: liver failure, liver dysfunction.

Application for impaired renal function

Contraindicated in renal failure or impaired renal function (CC less than 60 ml / min), in acute conditions occurring with the risk of developing impaired renal function, incl. dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (for example, respiratory and urinary tract infections), shock.

Application in children

Contraindicated in children and adolescents under 18 years of age due to the lack of data on the use.

Use in elderly patients

The drug should be used with caution in patients over the age of 60 who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them.

special instructions

Lactic acidosis

Lactic acidosis is an extremely rare but serious complication (high mortality in the absence of urgent treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis in patients receiving metformin occurred mainly in patients with diabetes mellitus with severe renal failure. Other associated risk factors should also be considered, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure, and any condition associated with severe hypoxia. This can help reduce the incidence of lactic acidosis. The risk of developing lactic acidosis should be taken into account when non-specific signs appear, such as muscle cramps, accompanied by dyspeptic disorders, abdominal pain and severe asthenia.Lactic acidosis is characterized by severe malaise with general weakness, acidotic dyspnea, vomiting, abdominal pain, muscle cramps, and hypothermia followed by coma. Diagnostic laboratory parameters are decreased blood pH (<7.25), plasma lactate concentration> 5 mmol / L, increased anion gap and lactate / pyruvate ratio. If you suspect lactic acidosis, you must stop taking the drug and immediately consult a doctor.If you suspect lactic acidosis, you must stop taking the drug and immediately consult a doctor.If you suspect lactic acidosis, you must stop taking the drug and immediately consult a doctor.

Surgical operations

The use of metformin should be discontinued 48 hours before elective surgery and can be continued no earlier than 48 hours after, provided that the renal function was found to be normal during the examination.

Kidney function

Since metformin is excreted by the kidneys, before starting treatment, and regularly thereafter, it is necessary to determine CC: at least once a year in patients with normal renal function, and 2-4 times a year in elderly patients, as well as in patients with CC on the lower limit of the norm. Special care should be taken in case of possible impairment of renal function in elderly patients of age with the simultaneous use of antihypertensive drugs, diuretics or NSAIDs. Heart failure Patients with heart failure have a higher risk of developing hypoxia and renal failure. Patients with chronic heart failure should regularly monitor cardiac and renal function while taking metformin.Reception of metformin in acute heart failure and chronic heart failure with unstable hemodynamic parameters is contraindicated.

Other precautions

Patients are advised to continue on a regular carbohydrate diet throughout the day. Overweight patients are advised to continue to follow a hypocaloric diet (but not less than 1000 kcal / day). Patients should also exercise regularly. Patients should inform the physician of any treatment they are taking and of any infectious diseases such as colds, respiratory tract infections, or urinary tract infections. It is recommended that routine laboratory tests be performed regularly to control diabetes. Metformin alone does not cause hypoglycemia, but caution is advised when using it in combination with insulin or other oral hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide, etc.).Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, heart palpitations, blurred vision, or impaired concentration. It is necessary to warn the patient that the inactive components of the drug Glucophage Long can be excreted unchanged through the intestine, which does not affect the therapeutic activity of the drug.

Influence on the ability to drive vehicles and mechanisms

Monotherapy with GlucophageЃ Long does not cause hypoglycemia, therefore it does not affect the ability to drive vehicles and mechanisms. Nevertheless, hypoglycemia may develop when metformin is used in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide, etc.). When symptoms of hypoglycemia appear, do not drive vehicles and mechanisms.

Overdose

When metformin was used at a dose of 85 g (42.5 times the maximum daily dose), the development of hypoglycemia was not observed, however, in this case, the development of lactic acidosis was observed. Significant overdose or associated risk factors can lead to the development of lactic acidosis. Treatment: if signs of lactic acidosis appear, treatment with the drug should be stopped immediately, the patient should be urgently hospitalized and, having determined the concentration of lactate, the diagnosis should be clarified. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also carried out.

Drug interactions

Contraindicated combinations Iodine-containing X-ray contrast agents: against the background of functional renal failure in patients with diabetes mellitus, radiological examination using iodine-containing X-ray contrast agents can cause the development of lactic acidosis. Glucophage Long must be canceled, depending on renal function, 48 hours before or at the time of X-ray examination using iodine-containing X-ray contrast media and resumed no earlier than 48 hours after, provided that the renal function was recognized as normal during the examination. Combinations not recommended Alcohol. In acute alcohol intoxication, the risk of developing lactic acidosis increases, especially in the case of: malnutrition, adherence to a low-calorie diet; liver failure.While taking the drug, you should avoid taking alcohol and medicines containing ethanol. Combinations requiring caution Medicines with indirect hyperglycemic action (eg, corticosteroids and tetracosactide (systemic and local), beta2-adrenergic agonists, danazol, chlorpromazine when taken in high doses (100 mg per day) and diuretics): more frequent monitoring may be required the concentration of glucose in the blood, especially at the beginning of treatment. If necessary, the dose of the drug Glucophage Long can be adjusted during treatment and after its termination, based on the level of glycemia. Diuretics: Concomitant use of loop diuretics can lead to the development of lactic acidosis due to possible functional renal failure. With the simultaneous use of the drug Glucophage Long with sulfonylurea derivatives,insulin, acarbose, salicylates, hypoglycemia may develop. Nifedipine increases the absorption and Cmax of metformin. Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin) secreted in the renal tubules compete with metformin for tubular transport systems and can lead to an increase in its Cmax. Colesevelam, when used simultaneously with metformin in the form of prolonged-release tablets, increases the concentration of metformin in blood plasma (increase in AUC without a significant increase in Cmax).secreted in the renal tubules, compete with metformin for tubular transport systems and can lead to an increase in its Cmax. Colesevelam, when used simultaneously with metformin in the form of prolonged-release tablets, increases the concentration of metformin in blood plasma (increase in AUC without a significant increase in Cmax).secreted in the renal tubules, compete with metformin for tubular transport systems and can lead to an increase in its Cmax. Colesevelam, when used simultaneously with metformin in the form of prolonged-release tablets, increases the concentration of metformin in blood plasma (increase in AUC without a significant increase in Cmax).