Metformin Sanofi 850 mg 60 coated tablets

Type 2 diabetes mellitus, especially in patients with obesity, when diet therapy and physical activity are ineffective:
• in adults as monotherapy or in combination with other oral hypoglycemic agents or with insulin;
• in children from 10 years of age as monotherapy or in combination with insulin.
Prevention of type 2 diabetes mellitus in patients with prediabetes with additional risk factors for the development of type 2 diabetes mellitus, where lifestyle changes have not achieved adequate glycemic control.

Administer orally.
Adults
Monotherapy and combination therapy with other oral hypoglycemic agents in type 2 diabetes:
• The usual starting dose is 500 mg or 850 mg 2-3 times a day after or during meals.
• Every 10-15 days, it is recommended to adjust the dose based on plasma glucose concentration measurements. Gradual dose increases help reduce gastrointestinal side effects.
• The maintenance dose of the drug is usually 1500-2000 mg/day. To reduce gastrointestinal side effects, the daily dose should be divided into 2-3 doses. The maximum dose is 3000 mg/day, divided into 3 doses.
• Patients taking metformin at doses of 2000-3000 mg per day may be switched to metformin at a dose of 1000 mg. The maximum recommended dose is 3000 mg per day, divided into 3 doses.
In case of planning to switch from another hypoglycemic agent: it is necessary to discontinue the other agent and start taking Metformin Sanofi at the dose indicated above.
Combination with insulin
For better blood glucose control, metformin and insulin can be used in combination therapy for patients with type 2 diabetes. The usual starting dose of Metformin Sanofi is 500 mg or 850 mg 2-3 times a day, while the insulin dose is adjusted based on blood glucose concentration levels.
Monotherapy for prediabetes
The usual dose is 1000-1700 mg per day after or during meals, divided into 2 doses.
Regular glycemic monitoring is recommended to assess the need for continued use of the drug.
Special patient groups
Children and adolescents
In children aged 10 years and older, metformin can be used either as monotherapy or in combination with insulin. The usual starting dose is 500 mg or 850 mg once a day after or during meals. After 10-15 days, the dose should be adjusted based on blood glucose concentration. The maximum daily dose is 2000 mg, divided into 2-3 doses.
Patients with renal insufficiency
Metformin can be used in patients with renal insufficiency with a creatinine clearance (CC) of 30-59 ml/min only in the absence of conditions that may increase the risk of lactic acidosis.
Renal function (CC) should be assessed before starting metformin therapy and at least once a year thereafter. In patients at increased risk of worsening renal insufficiency and in elderly patients, renal function should be assessed more frequently (every 3-6 months).
In cases of CC < 30 ml/min, the use of metformin is contraindicated (see "Contraindications" section). CC (ml/min) Maximum daily dose of metformin (divided into 2-3 doses per day) Additional information 60-89 3000 mg Due to decreased renal function, consideration should be given to reducing the metformin dose. 45-59 2000 mg Before starting metformin therapy, factors increasing the risk of lactic acidosis should be studied (see "Special Precautions" section). The starting dose is half of the maximum daily dose. 30-44 1000 mg < 30 - The use of metformin is contraindicated. Elderly patients Due to the possible decrease in renal function, the metformin dose should be adjusted under regular monitoring of renal function parameters (serum creatinine concentration should be determined at least 2-4 times a year). Duration of treatment The drug should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

1 tablet contains:
active ingredient: metformin hydrochloride - 850 mg;
excipients: core: hypromellose - 30.0 mg, povidone K 25 - 45.0 mg, magnesium stearate - 5.0 mg; film coating: hypromellose - 10.0 mg; macrogol 6000 - 2.0 mg; titanium dioxide (E 171) - 8.0 mg.

Elongated tablets with beveled edges, tapering towards the middle on both sides, coated in white, with a score line for division on both sides.
Appearance on fracture: from white to almost white.

• hypersensitivity to metformin or any excipient in the formulation;
• any type of acute metabolic acidosis (e.g., lactic acidosis, diabetic ketoacidosis), diabetic precoma, coma;
• renal insufficiency or impaired kidney function (creatinine clearance (CC) less than 30 ml/min);
• acute conditions with a risk of impaired kidney function: dehydration (due to diarrhea, vomiting), severe infectious diseases, shock;
• clinically significant manifestations of acute or chronic diseases that may lead to tissue hypoxia (including acute heart failure, chronic heart failure with unstable hemodynamic parameters, respiratory failure, acute myocardial infarction);
• extensive surgical operations and injuries when insulin therapy is indicated (see "Special Instructions" section);
• liver failure, impaired liver function;
• chronic alcoholism, acute alcohol poisoning;
• pregnancy;
• lactic acidosis (including in history);
• use within 48 hours before and 48 hours after radioisotope or radiological studies involving iodine-containing contrast agents (see "Interactions with Other Medications" section);
• adherence to a hypocaloric diet (less than 1000 kcal/day).
With caution
• in patients over 60 years old performing heavy physical work, which is associated with an increased risk of developing lactic acidosis;
• in patients with renal insufficiency (creatinine clearance (CC) 30-59 ml/min);
• during breastfeeding;
• in children aged 10 to 12 years.
Use during pregnancy and breastfeeding
Pregnancy
Decompensated diabetes during pregnancy is associated with an increased risk of congenital malformations and perinatal mortality. Limited data suggest that metformin use in pregnant women does not increase the risk of congenital malformations in the fetus.
When planning a pregnancy, as well as in the event of pregnancy occurring while taking metformin for prediabetes and type 2 diabetes, metformin should be discontinued, and insulin therapy should be initiated in the case of type 2 diabetes. It is necessary to maintain plasma glucose levels as close to normal as possible to reduce the risk of developmental defects in the fetus.
Breastfeeding
Metformin passes into breast milk. Adverse reactions (AR) in newborns during breastfeeding while taking metformin have not been observed. However, due to limited data, the use of the drug during breastfeeding is not recommended. The decision to discontinue breastfeeding should be made considering the benefits of breastfeeding and the potential risk of AR in the child.

Lactic Acidosis
Lactic acidosis is a very rare but serious complication (high mortality in the absence of emergency treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis during metformin use have primarily occurred in patients with diabetes and severe renal insufficiency.
Other associated risk factors should be considered, such as decompensated diabetes, ketosis, prolonged fasting, alcoholism, liver failure, and any condition associated with severe hypoxia. This may help reduce the frequency of lactic acidosis cases.
The risk of developing lactic acidosis should be considered when nonspecific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain, and pronounced asthenia. Lactic acidosis is characterized by acidotic dyspnea, abdominal pain, and hypothermia leading to subsequent coma. Diagnostic laboratory indicators include a decrease in blood pH (less than 7.25), plasma lactate levels above 5 mmol/L, increased anion gap, and lactate/pyruvate ratio. If metabolic acidosis is suspected, the medication should be discontinued, and a doctor should be consulted immediately.

Administration of Iodine-Containing Radiocontrast Agents
Intravenous administration of iodine-containing radiocontrast agents may lead to contrast-induced nephropathy, resulting in the accumulation of metformin, which increases the risk of lactic acidosis. Metformin therapy should be discontinued before, during, and for 48 hours after radioisotope or radiological studies; metformin therapy can only be resumed after re-evaluating kidney function in the absence of signs of deterioration (see the section "Interactions with Other Medications").

Surgical Operations
The use of metformin should be discontinued during surgical procedures under general, spinal, or epidural anesthesia. Metformin therapy may be resumed no earlier than 48 hours after the surgical procedure or resumption of food intake, provided that kidney function has been assessed and deemed normal.

Kidney Function
Since metformin is excreted by the kidneys, creatinine clearance should be determined before starting treatment and regularly thereafter:
• at least once a year for patients with normal kidney function;
• every 3-6 months for patients with creatinine clearance of 45-59 mL/min;
• every 3 months for patients with creatinine clearance of 30-44 mL/min.
The use of Metformin Sanofi is contraindicated in patients with creatinine clearance < 30 mL/min. Particular caution should be exercised in the presence of possible kidney function impairment in elderly patients, in dehydration (chronic or severe diarrhea, multiple episodes of vomiting), and with concurrent use of antihypertensive medications, diuretics, or non-steroidal anti-inflammatory drugs.Heart Failure Patients with heart failure have a higher risk of developing hypoxia and renal insufficiency. Patients with chronic heart failure should have regular monitoring of heart function and kidney function during metformin therapy. The use of metformin in heart failure with unstable hemodynamic parameters is contraindicated.Children and Adolescents The diagnosis of type 2 diabetes must be confirmed before starting metformin treatment. In clinical studies lasting 1 year, metformin was shown not to affect growth and sexual maturation. However, due to the lack of long-term data, careful monitoring of the subsequent effects of metformin on these parameters in children, especially during puberty, is recommended. The most careful monitoring is necessary for children aged 10-12 years.Other Precautions • Patients are advised to continue following a diet with even carbohydrate consumption throughout the day. Overweight patients are recommended to follow a hypocaloric diet (but not less than 1000 kcal/day). • Regular standard laboratory tests are recommended to monitor diabetes. • Metformin as monotherapy does not cause hypoglycemia; however, caution is advised when used in combination with insulin or other hypoglycemic agents (e.g., sulfonylurea derivatives, repaglinide, etc.). The use of Metformin Sanofi in patients with prediabetes is recommended in the presence of additional risk factors for the development of overt type 2 diabetes, which include: - age under 60 years; - body mass index (BMI) < 30 kg/m²; - history of gestational diabetes; - family history of diabetes in first-degree relatives; - elevated triglyceride levels; - decreased HDL cholesterol levels; - arterial hypertension. Metformin did not affect the fertility of male or female rats when administered at doses three times the maximum recommended daily dose for humans.Effect on the Ability to Drive and Operate Machinery The use of metformin in monotherapy does not affect the ability to drive and operate machinery. When metformin is combined with other hypoglycemic agents (sulfonylurea derivatives, insulin, meglitinides, etc.), patients should be warned about the possibility of developing hypoglycemic states, which may impair the ability to drive and engage in other potentially dangerous activities requiring increased attention and rapid psychomotor responses.

The frequency of adverse reactions (AR) was determined according to the classification of the World Health Organization: very common (≥ 1/10); common (≥ 1/100 and < 1/10); uncommon (≥ 1/1000 and < 1/100); rare (≥ 1/10000 and < 1/1000); very rare (< 1/10000); frequency unknown (cannot be estimated based on available data). AR are presented in order of decreasing significance.Metabolism and nutrition disorders: very rare - lactic acidosis (see section "Special Instructions"). Prolonged use of metformin may result in decreased absorption of vitamin B12. In patients with megaloblastic anemia, the possibility of this etiology should be considered.Nervous system disorders: common - taste disturbance. Gastrointestinal disorders: very common - nausea, vomiting, diarrhea, abdominal pain, loss of appetite. These adverse effects most often occur at the beginning of therapy and in most cases resolve spontaneously. To prevent their occurrence, it is recommended to take metformin 2 or 3 times a day during or after meals. Gradual dose escalation may improve gastrointestinal tolerance.Skin and subcutaneous tissue disorders: very rare - skin reactions such as erythema, pruritus, skin rash. Liver and biliary tract disorders: very rare - elevated liver function tests, hepatitis; these AR completely disappear after discontinuation of metformin.Children and adolescents Published data, post-marketing data, and results from controlled clinical trials in a limited pediatric population aged 10-16 years show that AR in children are similar in nature and severity to those in adult patients.Symptoms When administered at a dose of 85 g (42.5 times the maximum daily dose), hypoglycemia was not observed. However, in this case, lactic acidosis developed. Significant overdose or associated risk factors may lead to the development of lactic acidosis (see the "Special Precautions" section). Treatment In the event of signs of lactic acidosis, metformin treatment must be immediately discontinued, the patient should be urgently hospitalized, plasma lactate concentration should be determined, and the diagnosis confirmed. The most effective measure for eliminating lactate and metformin from the body is hemodialysis. Symptomatic treatment should also be provided.Contraindicated Combinations Iodine-containing radiopaque agents In patients with diabetes and functional renal insufficiency, radiological studies using iodine-containing radiopaque agents may lead to the development of lactic acidosis. Metformin should be discontinued based on renal function 48 hours before or during the radiological study using iodine-containing radiopaque agents and should not be resumed earlier than 48 hours after, provided that renal function was deemed normal during the examination.Not Recommended Combinations Alcohol In cases of acute alcohol intoxication, the risk of lactic acidosis increases, especially in the presence of: • inadequate nutrition, adherence to a low-calorie diet; • liver insufficiency. During treatment with the drug, it is advised to refrain from consuming alcohol and taking medications containing ethanol.Caution Required Combinations Danazol Simultaneous use of danazol is not recommended to avoid its hyperglycemic effect. If treatment with danazol is necessary, and after discontinuation, a dose adjustment of metformin is required under blood glucose concentration monitoring.Chlorpromazine When taken in high doses (100 mg per day), it increases blood glucose concentration by reducing insulin release. During treatment with neuroleptics and after discontinuation, a dose adjustment of the drug is required under blood glucose concentration monitoring.Glucocorticoids (GC) Systemic and local GCs reduce glucose tolerance, increase blood glucose concentration, and may sometimes cause ketosis. During treatment with GCs and after their discontinuation, a dose adjustment of metformin is required under blood glucose concentration monitoring.Diuretics Simultaneous use of "loop" diuretics may lead to the development of lactic acidosis due to possible functional renal insufficiency. Metformin should not be prescribed if creatinine clearance is below 60 ml/min.Beta2-adrenergic agonists in injection form Increase blood glucose concentration due to stimulation of beta2-adrenergic receptors. In this case, blood glucose concentration monitoring is necessary. If needed, insulin administration is recommended. When using the above-mentioned medications simultaneously, more frequent blood glucose concentration monitoring may be required, especially at the beginning of treatment. If necessary, the metformin dose may be adjusted during and after treatment.Antihypertensive medications, except for angiotensin-converting enzyme inhibitors, may lower blood glucose concentration. If necessary, the metformin dose should be adjusted. When metformin is used simultaneously with sulfonylurea derivatives, insulin, acarbose, or salicylates, hypoglycemia may occur. Nifedipine increases the absorption and Cmax of metformin. Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) secreted in renal tubules compete with metformin for tubular transport systems and may lead to an increase in its Cmax.Organic Cation Transporters (OCT) Metformin is a substrate for both OCT1 and OCT2 transporters. Simultaneous use of metformin with: • OCT1 inhibitors (verapamil) may reduce the effectiveness of metformin; • OCT1 inducers (rifampicin) may increase the absorption of metformin in the gastrointestinal tract and its effectiveness; • OCT2 inhibitors (cimetidine, dolutegravir, ranolazine, trimethoprim, crizotinib, olaparib, vandetanib, daclatasvir) may reduce the renal elimination of metformin and thus lead to an increase in its concentration in plasma.Therefore, caution is recommended, especially in patients with renal insufficiency, when using these medications simultaneously with metformin, as there may be an increase in metformin concentration in plasma. If necessary, consideration may be given to adjusting the metformin dose, as OCT inhibitors/inducers may alter its effectiveness. Some medications can exert a hyperglycemic effect and lead to worsening glycemic control. Such medications include phenothiazines, glucagon, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, isoniazid, slow calcium channel blockers, and thyroid hormones. When the above-mentioned medications are used simultaneously in patients receiving metformin, a decrease in antihyperglycemic efficacy may occur.

Metformin reduces hyperglycemia without leading to the development of hypoglycemia. Unlike sulfonylurea derivatives, metformin does not stimulate insulin secretion and does not have a hypoglycemic effect in healthy individuals.
It increases the sensitivity of peripheral receptors to insulin and the utilization of glucose by cells. It decreases glucose production by the liver by inhibiting gluconeogenesis and glycogenolysis. It delays the absorption of glucose in the intestine.
Metformin stimulates the synthesis of intracellular glycogen by acting on glycogen synthase. It increases the transport capacity of all types of glucose membrane transporters.
Additionally, metformin has a beneficial effect on lipid metabolism: it reduces total cholesterol, low-density lipoprotein levels, and triglycerides.
With metformin use, the patient's body weight either remains stable or decreases moderately.
Clinical studies have also shown the effectiveness of metformin for the prevention of type 2 diabetes in patients with prediabetes with additional risk factors for the development of overt type 2 diabetes, in whom lifestyle changes did not achieve adequate glycemic control.

Absorption and Distribution
After oral administration, metformin is sufficiently absorbed from the gastrointestinal tract (GIT). The absolute bioavailability is 50-60%. The maximum concentration (Cmax) (approximately 2 mcg/ml or 15 micromoles) in the plasma is reached after 2.5 hours. When taken with food, the absorption of metformin is reduced and delayed.
Metformin is rapidly distributed in tissues and is almost not bound to plasma proteins.
Metabolism and Excretion
It undergoes very little metabolism and is excreted by the kidneys. The clearance of metformin in healthy volunteers is more than 400 ml/min (4 times greater than creatinine clearance), indicating the presence of active tubular secretion. The half-life (T1/2) is approximately 6.5 hours.
In cases of renal insufficiency, T1/2 increases and the risk of drug accumulation rises.