Glucophage® long
The drug is taken orally. The tablets are swallowed whole, without chewing, with a small amount of water.
Extended-release tablets 500 mg
The drug is taken during dinner (1 time/day) or during breakfast and dinner (2 times/day). The tablets should only be taken with meals.
The dose of the drug is determined based on the glucose content in the blood plasma.
Monotherapy and combination therapy in combination with other hypoglycemic agents
The drug Glucophage® Long is prescribed in an initial dose of 500 mg (1 tablet) 1 time/day during dinner. When switching from Glucophage® (tablets with regular release of the active substance), the initial dose of Glucophage® Long should be equal to the daily dose of Glucophage®.
Dose titration: depending on the glucose level in the blood plasma, every 10-15 days the dose is slowly increased by 500 mg to the maximum daily dose.
The maximum daily dose of Glucophage® Long is 2 g (4 tablets) 1 time per day during dinner.
If glucose control is not achieved with the maximum daily dose taken once a day, then you can consider dividing this dose into several doses per day according to the following scheme: 2 tablets. during breakfast and 2 tab. during dinner.
When using the drug Glucophage® Long together with insulin
the usual initial dose of the drug is 500 mg (1 tablet) 1 time / day, and the dose of insulin is selected based on the results of measuring glucose levels in the blood plasma.
Glucophage® Long should be taken daily, without interruption. If treatment is stopped, the patient must inform the doctor.
If you miss a dose, the next dose should be taken at the usual time. You cannot double the dose of the drug.
Extended-release tablets 750 mg
The drug is taken during dinner (1 time/day).
Monotherapy and combination therapy in combination with other hypoglycemic agents
The initial dose is usually 1 tablet. 1 time/day
After 10-15 days of treatment, the dose must be adjusted based on the results of measuring blood glucose concentrations. Slowly increasing the dose helps reduce gastrointestinal side effects.
The recommended dose of the drug is 1.5 g (2 tablets) 1 time/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 - 2.25 g (3 tablets) 1 time / day.
If adequate glycemic control is not achieved when taking 3 tablets. 750 mg 1 time / day, then it is possible to switch to metformin with the usual release of the active substance with a maximum daily dose of 3 g.
For patients already receiving treatment with metformin tablets, the initial dose of Glucophage Long should be equivalent to the daily dose of regular-release tablets. Patients taking metformin in the form of regular-release tablets in a dose exceeding 2 g are not recommended to switch to Glucophage Long.
If you are planning a transition from another hypoglycemic agent: you must stop taking the other drug and start taking Glucophage® Long at the dose indicated above.
Combination with insulin
To achieve better control of blood glucose concentrations, metformin and insulin can be used in combination therapy. The usual starting dose of Glucophage® Long is 1 tablet. 750 mg 1 time/day during dinner, with the dose of insulin selected based on the results of measuring blood glucose levels.
Special patient groups
In elderly patients and patients with reduced renal function
The dose is adjusted based on an assessment of renal function, which must be carried out regularly at least 2 times a year.
Glucophage® Long should not be used in children and adolescents under 18 years of age.
due to lack of data on use.
Glucophage Long, 750 mg, extended-release tablets, 30 pcs.
Lactic acidosis
Lactic acidosis is a rare but serious (high mortality unless promptly treated) complication that may occur due to accumulation of metformin. Cases of lactic acidosis when taking metformin occurred mainly in diabetic patients with severe renal failure.
Other associated risk factors should be taken into account, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia. This may 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 shortness of breath and vomiting, abdominal pain, muscle cramps and hypothermia followed by coma. Diagnostic laboratory parameters are a decrease in blood pH (less than 7.25), plasma lactate concentration over 5 mmol/l, increased anion gap and lactate/pyruvate ratio. If lactic acidosis is suspected, stop taking the drug and consult a doctor immediately.
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 renal function has been 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 the content and/or Cl of creatinine in the serum: 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 Cl creatinine at the lower limit of normal.
In case of creatinine clearance less than 45 ml/min, the use of the drug is contraindicated.
Particular caution should be exercised in case of possible impairment of renal function in elderly patients, with 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 CHF should regularly monitor cardiac and renal function while taking metformin. Taking metformin in acute heart failure and CHF with unstable hemodynamic parameters is contraindicated.
Other Precautions
Patients are advised to continue to follow a diet with even carbohydrate intake throughout the day. Overweight patients are recommended to continue to follow a hypocaloric diet (but not less than 1000 kcal/day). Patients should also exercise regularly.
Patients should inform their physician about any treatment they are undergoing and any infectious diseases such as colds, respiratory tract infections, or urinary tract infections.
It is recommended that routine laboratory tests be performed regularly to monitor diabetes mellitus.
Metformin does not cause hypoglycemia when used alone, but caution is recommended when used in combination with insulin or other oral hypoglycemic agents (for example, sulfonylureas or repaglinide, etc.). Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, blurred vision, or difficulty concentrating. It is necessary to warn the patient that the inactive components of the drug Glucophage® Long can be excreted unchanged through the intestines, which does not affect the therapeutic activity of the drug.
Impact on the ability to drive vehicles and machinery.
Monotherapy with Glucophage® Long does not cause hypoglycemia and therefore does not affect the ability to drive vehicles and operate machinery.
However, it is possible to develop hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide, etc.). If symptoms of hypoglycemia appear, you should not drive vehicles or machinery.
Glucophage Long tablet prolong 1000 mg x60
Glucophage Long tablet prolong 1000 mg x60, ATX code: A10BA02 (Metformin) Active substance: metformin (metformin) Rec.INN registered by WHO
Dosage form
Glucophage® Long
Tab. with prolonged release 1000 mg: 28, 30, 56 or 60 pcs.reg. No.: LP-002396 from 03/12/14 - Indefinitely Re-registration date: 03/13/19
Release form, packaging and composition of the drug Glucophage® Long
Extended-release tablets are white or off-white, capsule-shaped, biconvex, debossed with “1000” on one side and “MERCK” on the other.
1 tab.
metformin hydrochloride 1000 mg
Excipients: carmellose sodium - 50 mg, hypromellose 2208 - 392.3 mg, magnesium stearate - 7 mg.
Clinical-pharmacological group: Hypoglycemic drug of the biguanide group for oral use Pharmaco-therapeutic group: Hypoglycemic drug for oral use of the biguanide group
pharmachologic effect
Metformin is a biguanide with a hypoglycemic effect, reducing both basal and postprandial plasma glucose levels. It does not stimulate insulin secretion and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral receptors to insulin and the utilization of glucose by cells. Reduces liver glucose production 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 (range 4-10 hours) after a single oral dose of 1 tablet of Glucophage Long in the dosage form of a 1000 mg extended-release tablet.
At steady state, identical to that of regular-release metformin, Cmax and AUC increase disproportionately to dose. Following a single oral dose of metformin extended-release tablets at a dose of 2000 mg, the AUC is similar to that observed after administration of metformin regular-release tablets at a dose of 1000 mg twice daily.
Intra-individual variability in Cmax and AUC following administration of metformin extended-release tablets is similar to that observed after administration of regular-release tablets.
When metformin extended-release tablets are administered at a dose of 1000 mg after meals, AUC increases by 77% (Cmax and TCmax increase by approximately 1 hour).
The absorption of metformin from extended-release tablets does not change depending on the composition of the food taken.
No accumulation is observed with repeated administration of metformin in the form of extended-release tablets at a dose of up to 2000 mg.
Distribution
Communication with plasma proteins is negligible. Cmax in the blood is lower than Cmax in plasma and is achieved after approximately the same time. Average Vd ranges from 63-276 hp.
Metabolism
No metabolites have been detected in humans.
Removal
Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is >.400 ml/min, indicating that metformin is eliminated 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 CC, T1/2 increases, which can lead to an increase in the concentration of metformin in plasma.
Indications for the drug Glucophage® Long
Type 2 diabetes mellitus in adults, especially in obese patients, with ineffective diet therapy and exercise:
as monotherapy, in combination with other oral hypoglycemic agents or with insulin.
Dosage regimen
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 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. Glucophage Long 1000 mg is prescribed as maintenance therapy for patients taking metformin in the form of regular-release tablets at a dose of 1000 mg or 2000 mg. To switch to Glucophage Long 1000 mg, the daily dose must be equivalent to the daily dose of metformin regular release. Patients taking metformin in the form of regular-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 starting dose of Glucophage Long is 500 mg or 750 mg once a day with dinner (the following formulations of Glucophage Long are available: extended-release tablets 500 mg and 750 mg). Every 10-15 days, it is recommended to adjust the dose based on the results of measuring blood glucose concentrations. Slowly increasing the dose promotes better gastrointestinal tolerability. In case of switching from another hypoglycemic agent, dose selection is carried out as described above, starting with the administration 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 500 mg or 750 mg tablet once a day with dinner, while the insulin dose is adjusted based on the results of measuring blood glucose concentrations. Then it is possible to switch to Glucophage® Long 1000 mg.
Daily dose
The maximum recommended dose of Glucophage® Long 1000 mg is 2 tablets per day (2000 mg). If adequate glycemic control cannot be achieved when taking the maximum recommended dose once a day, the maximum dose can be divided into two doses: 1 1000 mg tablet with breakfast and 1 1000 mg tablet with dinner. If adequate glycemic control is not achieved in this case, a switch to regular-release metformin (for example, Glucophage® film-coated tablets) with a maximum daily dose of 3000 mg is possible.
Patients with kidney failure
Metformin can be used in patients with moderate renal failure (creatinine clearance 45–59 ml/min) only in the absence of conditions that may increase the risk of developing lactic acidosis. The initial dose is 500 mg or 750 mg 1 time / day. The maximum dose is 1000 mg/day. Renal function should be carefully monitored every 3-6 months. If CC is below 45 ml/min, the drug should be stopped immediately.
Elderly patients
In elderly patients, the dose of metformin is adjusted based on assessment of renal function, which should be carried out regularly.
Duration of treatment
Glucophage® Long should be taken daily, without interruption. If treatment is stopped, the patient must inform the doctor.
Missing a dose
If a dose is missed, the patient should take the next dose at the usual time. You should not take a double dose of Glucophage® Long.
Side effect
The frequency of side effects of the drug is assessed as follows: very common: ≥1/10 common: ≥1/100, <.1/10 uncommon: ≥1/1000, <.1/100 rare: ≥1/10,000, <.1 /1000 very rare: ≤1/10,000
Metabolic and nutritional disorders
Very rarely - lactic acidosis. With long-term use of metformin, a decrease in the absorption of vitamin B12 may be observed. When megaloblastic anemia is detected, the possibility of such an etiology must be taken into account.
Nervous system disorders
Often - taste disturbance (metallic taste in the mouth).
Gastrointestinal disorders
Very common: nausea, vomiting, diarrhea, abdominal pain and lack of appetite. Most often they occur during the initial period of treatment and in most cases resolve spontaneously. To prevent symptoms, it is recommended to take metformin during or after meals. Slowly increasing the dose may improve gastrointestinal tolerability.
Disorders of the liver and biliary tract
Very rarely - abnormal liver function tests and hepatitis; after discontinuation of metformin, these adverse 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 listed in the instructions are noted, the patient should inform the doctor.
Contraindications for use
hypersensitivity to metformin or to any excipient, diabetic ketoacidosis, diabetic precoma, coma, renal failure or impaired renal function (creatinine clearance <.45 ml/min), acute conditions with a risk of developing renal dysfunction, incl. dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (for example, 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, liver dysfunction, chronic alcoholism, acute alcohol poisoning, lactic acidosis (including . and in the anamnesis), use for a period of less than 48 hours before and within 48 hours after radioisotope or x-ray studies with the introduction of an iodinated contrast agent (for example, intravenous urography), adherence to a hypocaloric diet (less than 1000 kcal/day), pregnancy, children under 18 years of age due to lack of data on use.
Use the drug with caution in patients over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis, in patients with renal failure (creatinine clearance 45-59 ml/min), and during breastfeeding.
Use during pregnancy and breastfeeding
Decompensated diabetes mellitus during 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 birth defects in children.
When planning pregnancy, as well as in the event of pregnancy while using metformin, the drug should be discontinued and insulin therapy should be prescribed. It is necessary to maintain blood glucose concentrations at a level as close to normal as possible to reduce the risk of fetal malformations.
Metformin is excreted in breast milk. No side effects were observed in breastfeeding newborns while taking metformin. However, due to limited data, the use of the drug during breastfeeding is not recommended. The decision to stop breastfeeding should be made taking into account the benefits of breastfeeding and the potential risk of side effects in the baby.
Use for liver dysfunction Contraindication: liver failure, liver dysfunction.
Use for renal impairment
Contraindicated in case of renal failure or impaired renal function (creatinine clearance less than 60 ml/min), in acute conditions with a risk of developing renal dysfunction, incl. dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (for example, respiratory and urinary tract infections), shock.
Use in children
Contraindicated in children and adolescents under 18 years of age due to the lack of data on use.
Use in elderly patients The drug should be used with caution in patients over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis.
special instructions
Lactic acidosis
Lactic acidosis is an extremely rare but serious complication (high mortality in the absence of immediate treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis in patients receiving metformin occurred mainly in diabetic patients with severe renal failure.
Other associated risk factors should be taken into account, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia. This may 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 shortness of breath, vomiting, abdominal pain, muscle cramps and hypothermia followed by coma. Diagnostic laboratory parameters are a decrease in blood pH (<.7.25), plasma lactate concentration >.5 mmol/l, increased anion gap and lactate/pyruvate ratio. If lactic acidosis is suspected, stop taking the drug and consult a doctor immediately.
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 renal function has been 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 lower limit of normal.
Particular caution should be exercised in case of possible impairment of renal function in elderly patients with 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 have cardiac and renal function monitored regularly while taking metformin.
Taking metformin in acute heart failure and chronic heart failure with unstable hemodynamic parameters is contraindicated.
Other Precautions
Patients are advised to continue to follow a diet with even carbohydrate intake throughout the day. Overweight patients are recommended to continue to follow a hypocaloric diet (but not less than 1000 kcal/day). Patients should also exercise regularly. Patients should inform their physician about any treatment they are undergoing and any infectious diseases such as colds, respiratory tract infections, or urinary tract infections. It is recommended that routine laboratory tests be performed regularly to monitor diabetes mellitus. Metformin does not cause hypoglycemia when used alone, but caution is recommended when used in combination with insulin or other oral hypoglycemic agents (for example, sulfonylureas or repaglinide, etc.). Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, blurred vision, or difficulty concentrating.
It is necessary to warn the patient that the inactive components of the drug Glucophage® Long can be excreted unchanged through the intestines, which does not affect the therapeutic activity of the drug.
Impact on the ability to drive vehicles and machinery
Monotherapy with Glucophage® Long does not cause hypoglycemia and therefore does not affect the ability to drive vehicles and machines.
However, it is possible to develop hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide, etc.). If symptoms of hypoglycemia appear, you should not drive vehicles or machinery.
Overdose
When using metformin at a dose of 85 g (42.5 times the maximum daily dose), the development of hypoglycemia was not observed, but 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 must be stopped immediately, the patient must be urgently hospitalized and, after determining the lactate concentration, the diagnosis must 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 radiocontrast 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 should be discontinued depending on renal function 48 hours before or during an X-ray examination using iodine-containing contrast agents and resumed no earlier than 48 hours after, provided that during the examination renal function was found to be normal.
Combinations not recommended
Alcohol. With acute alcohol intoxication, the risk of developing lactic acidosis increases, especially in the case of:
malnutrition, low-calorie diet, liver failure.
While taking the drug, you should avoid drinking alcohol and medications containing ethanol.
Combinations requiring caution
Medicines with indirect hyperglycemic effects (for example, corticosteroids and tetracosactide (systemic and local), beta2-agonists, danazol, chlorpromazine when taken in large doses (100 mg per day) and diuretics): more frequent monitoring of blood glucose concentrations may be required , especially at the beginning of treatment. If necessary, the dose of Glucophage Long can be adjusted during treatment and after its cessation, based on the level of glycemia.
Diuretics: Concomitant use of loop diuretics may lead to the development of lactic acidosis due to possible functional renal failure.
When using the drug Glucophage® Long simultaneously with sulfonylurea derivatives, insulin, acarbose, and 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 may lead to an increase in its Cmax.
Colesevelam, when used concomitantly with metformin in the form of extended-release tablets, increases the plasma concentration of metformin (increased AUC without a significant increase in Cmax).
Storage conditions for the drug Glucophage® Long
The drug should be stored out of the reach of children at a temperature not exceeding 30 °C.
Shelf life of the drug Glucophage® Long Shelf life - 3 years.
Terms of sale
The drug is available with a prescription.
