Metformin LONG 500 tablets MB 500mg

Name Metformin Long 500. Forms of release Tablets. INN Metformin. FTGHypoglycemic agent for oral use of the biguanide group. Composition One tablet contains: active ingredient: metformin hydrochloride – 500 mg; excipients: hypromellose, croscarmellose sodium, hypromellose K 100 M, microcrystalline cellulose, magnesium stearate. Pharmacotherapeutic group Medicines for the treatment of diabetes mellitus. Drugs for lowering blood glucose levels, except for insulin. ATX code: A10BA02. Pharmacological properties Pharmacodynamics Metformin is a biguanide with a hypoglycemic effect, which reduces both basal and postprandial glucose levels in blood plasma. 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 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 synthetase. Increases the transport capacity of all types of membrane glucose carriers. Pharmacokinetics Absorption After an oral dose in the form of a prolonged-release tablet, the absorption of metformin is slower than that of a regular-release tablet of metformin. The time to reach the maximum concentration (TCmax) is 7 hours. At the same time, the TCmax for the immediate release tablet is 2.5 hours. After a single oral administration of 2000 mg of metformin in the form of tablets of prolonged action, the area under the concentration-time curve (AUC) similar to that seen with metformin 1000 mg regular release tablets twice daily. Fluctuations in the maximum concentration of metformin (Cmax) and AUC in individual patients in the case of taking metformin in the form of tablets of prolonged action are comparable to the same indicators as in the case of taking tablets with a regular release profile. Metformin absorption from extended release tablets does not change with food intake. There is no cumulation with repeated administration of up to 2000 mg of metformin in the form of prolonged-release tablets. Distribution Communication with plasma proteins is negligible. Metformin partially binds to red blood cells. Cmax in the blood is lower than Cmax in plasma and is reached after about the same time. At usual therapeutic doses, accumulation of metformin in plasma is not observed, except in cases of impaired renal function. The average volume of distribution fluctuates in the range of 63 – 276 l. Metabolism Metformin is not involved in metabolism, and, since the relationship with plasma proteins is negligible, it is metabolized in an unbound form. No metabolites have been found in humans. Metformin is excreted unchanged by the kidneys. Excretion Renal clearance of metformin is >400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. After oral administration, the half-life is about 6.5 hours. With impaired renal function, metformin clearance decreases in proportion to creatinine clearance, the half-life increases, which can lead to an increase in plasma metformin concentration. Indications for use Type 2 diabetes mellitus in adults (especially in patients with overweight) with the ineffectiveness of diet therapy and exercise, as monotherapy or in combination with other oral hypoglycemic agents or together with insulin. Dosage and administration Monotherapy or combination therapy in combination with other oral hypoglycemic agents. The recommended initial dose is 1 tablet of Metformin Long 500 per day. After 10-15 days of treatment, the dose must be adjusted in accordance with the results of measurements of glucose levels in the blood serum. Slowly increasing the dose helps to reduce side effects from the digestive tract. The maximum recommended dose is 4 tablets of Metformin Long 500 per day (2000 mg). The dose of the drug is recommended to be taken once a day with meals in the evening, increasing by 500 mg every 10-15 days up to a maximum dose of 2000 mg. If, when using drugs Metformin Long at a maximum dose of 2000 mg 1 time per day, the required level of glycemia cannot be achieved, the dose taken can be divided into 2 doses (1 time in the morning and 1 time in the evening, during a meal). If after this the desired level of glycemia is not achieved, metformin tablets with immediate release can be used at the maximum recommended dose of 3000 mg per day. For patients already taking Metformin, the starting dose of Metformin Long should be equivalent to that of the immediate release tablets. For patients taking Metformin at a dose above 2000 mg, switching to Metformin Long is not recommended. In case of switching to the drug Metformin Long 500, it is necessary to stop taking another antidiabetic drug. Metformin Long 750 is intended for patients who are already receiving metformin immediate release tablets. The dose of Metformin Long 750 should be equivalent to the daily dose of metformin immediate release tablets with a maximum dose of 1500 mg in the evening with meals. Combination therapy in combination with insulin To achieve better control of blood glucose levels, metformin and insulin can be used as a combination therapy. Usually, the initial dose of Metformin Long 500 is 1 tablet per day with meals in the evening, while then the dose of insulin must be selected in accordance with the results of measuring blood glucose levels. For patients who have already received metformin and insulin in combination therapy, the dose of Metformin Long 750 should be equivalent to the daily dose of metformin with a maximum dose of 1500 mg in the evening during meals, while the insulin dose is adjusted based on blood glucose measurements. Elderly patients and those with reduced renal function Elderly patients and patients with reduced renal function should select the dose of metformin based on an assessment of renal function (see section “Precautions”). Metformin can be used to treat patients with a moderate decrease in creatinine clearance (60-89 ml / min), provided there are no other diseases that may increase the risk of developing lactic acidosis, with the following dose adjustments: – initial dose – 500 mg metformin hydrochloride once per day; – The maximum recommended dose is 1000 mg per day, divided into 2 doses. Kidney function during treatment should be carefully monitored (every 3 to 6 months); – if the level of creatinine clearance falls below 60 ml/min, treatment with metformin should be stopped immediately. Children Due to the lack of data on the use of drugs, Metformin Long should not be used in children under 18 years of age. Side effect Determination of the frequency of adverse reactions: very often (≥ 1/10), often (≥ 1/100, < 1/10), infrequently (≥ 1/1000, < 1/100), rarely (≥ 1/10,000, < 1/1000), very rare (≥ 1/10,000), isolated cases (cannot be estimated from the available data). Side effects are presented in decreasing order of importance: Nervous system Often: taste disturbance (metallic taste in the mouth - 3%). Gastrointestinal disorders Very common: nausea, vomiting, diarrhoea, abdominal pain and anorexia. Most often they occur in the initial period of treatment and in most cases resolve spontaneously. To prevent symptoms, it is recommended to take metformin during or after meals, dividing the daily dose into 2 doses per day. Slow dose escalation may improve gastrointestinal tolerance. If symptoms persist for a long time, stop taking the drug and consult a doctor. Skin and subcutaneous tissue Very rare: skin reactions such as erythema, pruritus, urticaria. Metabolic disorders Very rare: lactic acidosis (see Precautions section). In patients treated with metformin for a long time, there may be a decrease in the absorption of vitamin B12, accompanied by a decrease in its concentration in the blood serum. When megaloblastic anemia is detected, the possibility of such an etiology must be considered. Early symptoms of lactic acidosis are nausea, vomiting, diarrhea, a decrease in body temperature, abdominal pain, muscle pain, and in the future there may be an increase in breathing, dizziness, impaired consciousness and the development of coma. Hepato-biliary disorders There are isolated reports of abnormal liver function tests or hepatitis; after the abolition of metformin, adverse events completely disappear. If dyspeptic symptoms persist, treatment with metformin should be discontinued. Contraindications hypersensitivity to metformin hydrochloride or to any excipient; diabetic ketoacidosis, diabetic precoma, coma; renal failure or impaired renal function (creatinine clearance less than 60 ml / min); acute conditions occurring with a risk of developing impaired renal function; dehydration (with diarrhea, vomiting), fever, severe infectious diseases; conditions of hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases); clinically pronounced manifestations of acute and chronic diseases that can lead to the development of tissue hypoxia (including heart or respiratory failure, acute myocardial infarction); major surgery and trauma when insulin therapy is indicated (see Precautions section); liver failure, impaired liver function; chronic alcoholism, acute alcohol poisoning; pregnancy, breastfeeding period; lactic acidosis (including history); use for at least 2 days before and within 2 days after radioisotope or X-ray studies with the introduction of an iodine-containing contrast agent (see section "Interaction with other drugs"); adherence to a hypocaloric diet (less than 1000 cal / day); children under 18 years old. Caution Use the drug in people over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis in them. Overdose When using metformin at a dose of 85 g (42.5 times the maximum daily dose), no hypoglycemia was observed. However, in this case, the development of lactic acidosis was observed. Treatment: in case of signs of lactic acidosis, treatment with the drug should be stopped immediately, the patient should be urgently hospitalized and, having determined the concentration of lactate, clarify the diagnosis. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also carried out. Lactic acidosis is a medical emergency; treatment of lactic acidosis should be carried out in the clinic. The most effective treatment for removing lactate and metformin is hemodialysis. Interaction with other drugs Iodine-containing radiopaque agents: against the background of functional renal failure in patients with diabetes mellitus, a radiological examination using iodine-containing radiopaque agents can cause the development of lactic acidosis. The appointment of drugs Metformin Long should be canceled 48 hours before and not resumed earlier than 2 days after an x-ray examination using iodine-containing radiopaque agents, provided that during the examination, renal function was found to be normal. Not recommended combinations: drinking alcohol increases the risk of developing lactic acidosis during acute alcohol intoxication, especially in case of: malnutrition, low-calorie diet; liver failure. While taking the drug, alcohol and medicines containing ethanol should be avoided. Combinations requiring special care Danazol: the simultaneous use of danazol is not recommended in order to avoid the hyperglycemic effect of the latter. If necessary, treatment with danazol and after discontinuation of the latter requires dose adjustment of the drug Metformin Long under the control of glucose levels. Chlorpromazine: when taken in high doses (100 mg per day), it increases glycemia by reducing insulin release. In the treatment of neuroleptics and after discontinuation of the latter, a dose adjustment of Metformin Long is required under the control of glycemic levels. Glucocorticosteroids (GCS) of systemic and local action reduce glucose tolerance, increase glycemia, sometimes causing ketosis. In the treatment of corticosteroids, and after discontinuation of the latter, a dose adjustment of Metformin Long is required under the control of glycemic levels. Diuretics: concomitant use of loop diuretics can lead to the development of lactic acidosis due to possible functional renal failure. Metformin Long should not be prescribed if creatinine clearance is below 60 ml/min. Assigned as injections of beta-2 sympathomimetics: increase glycemia due to stimulation of beta-2 receptors. In this case, glycemic control is necessary. If necessary, the appointment of insulin is recommended. With the simultaneous use of the above drugs, more frequent monitoring of blood glucose levels may be required, especially at the beginning of treatment. If necessary, the dose of metformin can be adjusted during treatment and after its termination. Angiotensin-converting enzyme inhibitors and other antihypertensive drugs can lower blood glucose levels. If necessary, the dose of metformin should be adjusted. Drugs that affect organic cation transporters (OCTs) Metformin is a substrate for both organic cation transporters OST 1 and OST 2. Co-administration of metformin with: OCT1 inhibitors (eg verapamil) may reduce the effectiveness of metformin; OCT1 inducers (e.g. rifampicin) may increase the gastrointestinal absorption and efficacy of metformin. OCT2 inhibitors (such as cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may reduce renal excretion of metformin and thus lead to an increase in metformin plasma concentrations; inhibitors such as OCT1 and OCT2 (e.g. crizotinib, olaparib) may alter the efficacy of metformin. Particular caution should be exercised in patients with renal non-residuality if these medicinal products are co-administered with metformin, as plasma concentrations of metformin may increase. If dose adjustment of metformin is necessary, both inhibitors and inducers of OCT must be considered, as this may change the effectiveness of metformin. With the simultaneous use of drugs Metformin Long with sulfonylurea derivatives, insulin, acarbose, salicylates, an increase in the hypoglycemic effect is possible. 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 for tubular transport systems. Precautions Lactic acidosis Lactic acidosis is a rare but severe metabolic complication that may result from accumulation of metformin hydrochloride. Cases of lactic acidosis have been reported in patients with diabetes mellitus and severe renal failure. Risk factors for lactic acidosis: poorly controlled diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure, or any condition associated with hypoxia. Lactic acidosis is characterized by muscle cramps, acidotic dyspnea, abdominal pain and hypothermia, and coma may develop in the future. Laboratory signs of the development of lactic acidosis are an increase in the level of serum lactate more than 5 mmol / l, a decrease in blood pH against the background of electrolyte disturbances and an increase in the lactate / pyruvate ratio. If lactic acidosis is suspected, it is necessary to stop the use of the drug and immediately hospitalize the patient. Heart failure Patients with heart failure are at high risk of developing hypoxia and renal failure. In patients with stable chronic heart failure, metformin should only be used with regular monitoring of cardiac and renal function. Metformin is contraindicated in patients with acute and unstable heart failure (see section "Contraindications"). Surgery Metformin should be discontinued 48 hours before elective surgery and may be resumed no earlier than 48 hours after, provided that renal function was found to be normal during the examination. Iodine-containing radiopaque agents When performing radiological studies using radiopaque agents, it is necessary to stop the use of the drug Metformin Long 48 hours before the study and not resume earlier than 48 hours after the X-ray examination and assessment of renal function. Renal impairment Since metformin is excreted by the kidneys, before starting treatment and regularly thereafter, it is necessary to determine the content and / or clearance of serum creatinine: at least once a year in patients with normal renal function, and 2 to 4 times a year in elderly patients , as well as in patients with creatinine clearance at the lower limit of normal. Therapy with Metformin Long is recommended to start after assessing kidney function. With a decrease in creatinine clearance, kidney function should be monitored at least 2 to 4 times a year. Elderly patients Data on the effectiveness of metformin in patients 75 years of age and older are limited, so the appointment of metformin in this category of patients is not recommended. Other precautions Patients are advised to follow a diet with a regular distribution of carbohydrate intake throughout the day. Overweight patients should follow a hypocaloric diet. Metformin does not cause hypoglycemia when used alone, but caution is advised when it is used in combination with insulin or other oral hypoglycemic agents (eg, sulfonylurea derivatives, etc.). Standard laboratory tests should be performed regularly to control diabetes mellitus. It is necessary to warn the patient that the inactive components of the drug Metformin Long can be excreted unchanged through the intestines, which does not affect the therapeutic activity of the drug. Use during pregnancy and during breastfeeding When planning pregnancy, as well as in the event of pregnancy while taking Metformin Long, the drug should be canceled and insulin therapy should be prescribed. The patient should inform the doctor about the onset of pregnancy while taking Metformin Long. Since there are no data on the penetration of metformin into breast milk, this drug is contraindicated during breastfeeding. If necessary, the use of drugs Metformin Long during lactation, breastfeeding should be discontinued. Influence on the ability to drive a car and work with mechanisms Metformin Long monotherapy does not cause hypoglycemia, and therefore does not affect the ability to drive a car and work with mechanisms. However, patients should be warned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide). Use in Elderly Patients Particular caution should be exercised in the event of possible impairment of renal function in elderly patients, while the use of antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs. The dose is selected individually depending on the state of kidney function. The initial dose should be no more than one tablet per day, it is necessary to regularly monitor the state of kidney function. Use in children and adolescents Metformin Long is not recommended for use in children and adolescents. Upakovka10 tablets in a blister pack of PVC film and aluminum foil. 3 or 6 blister packs, together with the leaflet, are placed in a pack of cardboard. Storage conditions In a place protected from light and moisture, at a temperature not exceeding 25ºС. Keep out of the reach of children. Shelf life 2 years. Do not use after the expiration date. Conditions for dispensing from pharmacies By prescription MV 500mg