Glucophage Long tablets 1000mg, No. 30

Type 2 diabetes mellitus in adults, especially in obese patients, with ineffective diet and exercise:

• as monotherapy;

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

The drug Glucophage Long 1000 mg is taken orally. The tablets are swallowed whole, without chewing, with a sufficient amount of liquid, 1 time per day during or after dinner.

The dose of the drug Glucophage Long 1000 mg 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

• Glucophage Long 1000 mg should be taken once a day during or after dinner.

• The drug Glucophage Long 1000 mg is prescribed as maintenance therapy for patients taking metformin in the form of conventional-release tablets at a dose of 1000 mg or 2000 mg. To switch to Glucophage Long 1000 mg, its daily dose should be equivalent to the daily dose of metformin with normal release.

• Patients taking metformin in the form of conventional-release tablets at a dose exceeding 2000 mg are not recommended to switch to Glucophage Long 1000 mg.

• For patients not taking metformin, the recommended initial dose of Glucophage Long is 500 mg or 750 mg 1 time / day with dinner (the following Glucophage Long dosage forms are available: 500 mg and 750 mg sustained-release tablets). It is recommended to adjust the dose every 10-15 days based on the results of measuring the blood glucose concentration. A slow increase in dose contributes to better tolerance from the gastrointestinal tract.

• In the case of a transition from another hypoglycemic agent, the dose selection is carried out as described above, starting with the appointment of the drug Glucophage Long 500 mg or 750 mg, with a possible subsequent transition to the drug Glucophage Long 1000 mg.

Combination with insulin

To achieve better glycemic control, metformin and insulin can be used in combination therapy. The usual starting dose of Glucophage Long is one tablet of 500 mg or 750 mg 1 time / day during dinner, while the dose of insulin is selected based on the results of measuring the concentration of glucose in the blood. Further, it is possible to switch to GlucophageЃ Long 1000 mg.

Daily dose

The maximum recommended dose of Glucophage Long 1000 mg is 2 tablets per day (2000 mg). If, when taking the maximum recommended dose 1 time / day, it is not possible to achieve adequate glycemic control, the maximum dose can be divided into two doses: 1 tablet 1000 mg - during breakfast and 1 tablet 1000 mg - during dinner. If adequate glycemic control is not achieved in this case, it is possible to switch to conventional-release metformin (for example, GlucophageЃ 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 (CC 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis. The initial dose is 500 mg or 750 mg once a day. The maximum dose is 1000 mg / day. Kidney function should be closely monitored every 3-6 months. If CC is below 45 ml / min, the drug should be discontinued immediately.

Elderly patients

In elderly patients, the dose of metformin is adjusted based on the assessment of renal function, which should be performed regularly.

Duration 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.

Sustained-release tablets, white or off-white, capsule-shaped, biconvex, engraved with '1000' on one side and 'MERCK' on the other.

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 (CC <45 ml / min);

• acute conditions occurring with the risk of developing renal dysfunction, incl. dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (eg, respiratory and urinary tract infections), shock;

• clinically pronounced manifestations of acute and 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;

• liver failure, impaired liver function;

• chronic alcoholism, acute alcohol poisoning;

• lactic acidosis (including history);

• use for a period of 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 (for example, iv urography);

• adherence to a hypocaloric diet (less than 1000 kcal / day);

• pregnancy;

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

Use the drug 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; in patients with renal insufficiency (CC 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 prolonged 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 extended-release tablets 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.

In case of 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 the plasma.

Side effect

Metabolic and nutritional disorders

Very rarely - 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).

Gastrointestinal disorders

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 they spontaneously disappear. It is recommended to take metformin with or after meals to prevent symptoms. Slowly increasing the dose may improve gastrointestinal tolerance.

Liver and biliary tract disorders

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 treated with 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 nonspecific 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.

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.

Ћечение: в случае по¤влени¤ признаков лактоацидоза лечение препаратом необходимо немедленно прекратить, пациента срочно госпитализировать и, определив концентрацию лактата, уточнить диагноз. Ќаиболее эффективным меропри¤тием по выведению из организма лактата и метформина ¤вл¤етс¤ гемодиализ. ѕровод¤т также симптоматическое лечение.

Ћекарственное взаимодействие

ѕротивопоказанные комбинации

…одсодержащие рентгеноконтрастные средства: на фоне функциональной почечной недостаточности у пациентов с сахарным диабетом радиологическое исследование с применением йодсодержащих рентгеноконтрастных средств может вызывать развитие лактоацидоза. vлюкофажЃ Ћонг необходимо отменить в зависимости от функции почек за 48 ч до или на врем¤ рентгенологического исследовани¤ с применением йодсодержащих рентгеноконтрастных средств и возобновл¤ть не ранее 48 ч после, при условии, что в ходе обследовани¤ почечна¤ функци¤ была признана нормальной.

Ќерекомендуемые комбинации

јлкоголь. ѕри острой алкогольной интоксикации увеличиваетс¤ риск развити¤ лактоацидоза, особенно в случае:

• недостаточного питани¤, соблюдени¤ низкокалорийной диеты;

• печеночной недостаточности.

¬о врем¤ приема препарата следует избегать приема алкогол¤ и лекарственных средств, содержащих этанол.

 омбинации, требующие осторожности

Ћекарственные средства с непр¤мым гипергликемическим действием (например, v — и тетракозактид (системного и местного действи¤), бета2-адреномиметики, даназол, хлорпромазин при приеме в больших дозах (100 мг в день) и диуретики): может потребоватьс¤ более частый контроль концентрации глюкозы в крови, особенно в начале лечени¤. ѕри необходимости доза препарата vлюкофажЃ Ћонг может быть скорректирована в процессе лечени¤ и после его прекращени¤, исход¤ из уровн¤ гликемии.

?иуретики: одновременный прием 'петлевых' диуретиков может привести к развитию лактоацидоза из-за возможной функциональной почечной недостаточности.

ѕри одновременном применении препарата vлюкофажЃ Ћонг с производными сульфонилмочевины, инсулином, акарбозой, салицилатами возможно развитие гипогликемии.

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).