Metformin-Richter 500 Mg 60 Pcs Film Coated Tablets

Metformin-Richter tablets PPO 1000 mg No. 60

Compound

Active substance: metformin hydrochloride - 1000 mg. Excipients: copovidone, povidone K-30, siliconized microcrystalline cellulose, magnesium stearate.

Pharmacokinetics

Suction and distribution

After oral administration, metformin is absorbed from the gastrointestinal tract almost completely. Absolute bioavailability is 50-60%. Cmax in blood plasma (approximately 2 µg/ml or 15 µmol) is achieved after 2.5 hours. With simultaneous food intake, the absorption of metformin is reduced and slows down slightly. Metformin is quickly distributed into tissues and practically does not bind to plasma proteins.

Metabolism and excretion

It is metabolized to a very weak extent and is excreted by the kidneys. The clearance of metformin in healthy subjects is 400 ml/min (4 times more than CC), indicating the presence of active tubular secretion. T1/2 is approximately 6.5 hours. In case of renal failure, T1/2 increases, and there is a risk of drug accumulation.

Indications for use

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

in adults as monotherapy or in combination with other oral hypoglycemic agents, or with insulin;
in children over 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 developing type 2 diabetes mellitus in whom lifestyle changes have not allowed them to achieve adequate glycemic control.

Contraindications

hypersensitivity to metformin or to any excipient;
diabetic ketoacidosis, diabetic precoma, coma;
renal failure or impaired renal function (creatinine clearance less than 45 ml/min);
acute conditions with a risk of developing renal dysfunction: dehydration (with diarrhea, vomiting), severe infectious diseases, 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 surgical operations and injuries, when insulin therapy is indicated (see section “Special Instructions”);
liver failure, liver dysfunction;
chronic alcoholism, acute alcohol poisoning;
pregnancy;
lactic acidosis (including history);
use for less than 48 hours before and within 48 hours after radioisotope or x-ray studies with the introduction of an iodine-containing contrast agent (see section “Drug Interactions”);
lactose intolerance, lactase deficiency, glucose-galactose malabsorption;
adherence to a hypocaloric diet (less than 1000 kcal/day).

The drug should be used with caution:

in persons 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);
during breastfeeding.

Directions for use and doses

Use internally.

Adults:

Monotherapy and combination therapy in combination with other oral hypoglycemic agents for type 2 diabetes mellitus:

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 the results of measuring the concentration of glucose in the blood plasma. Slowly increasing the dose helps reduce gastrointestinal side effects.
The maintenance dose of the drug is usually 1500-2000 mg/day. To reduce side effects from the gastrointestinal tract, the daily dose should be divided into 2-3 doses. The maximum dose is 3000 mg/day, divided into three doses.
Patients taking metformin in doses of 2000-3000 mg/day can be switched to taking Metformin-Richter 1000 mg. The maximum recommended dose is 3000 mg/day, divided into 3 doses.

If you are planning a transition from taking another hypoglycemic drug, you must stop taking the other drug and start taking Metformin-Richter at the dose indicated above.

Combination with insulin

To achieve better blood glucose control, metformin and insulin can be used in combination therapy in patients with type 2 diabetes. The usual starting dose of Metformin-Richter is 500 mg or 850 mg 2-3 times a day, while the dose of insulin is selected based on the concentration of glucose in the blood.

Children and teenagers

In children over 10 years of age, Metformin-Richter can be used both in monotherapy and in combination with insulin. The usual starting dose is 500 mg or 850 mg once daily after or during meals. After 10-15 days, the dose should be adjusted based on the concentration of glucose in the blood. The maximum daily dose is 2000 mg, divided into 2-3 doses.

Monotherapy for prediabetes:

The usual dose is 1000-1700 mg per day after or during meals, divided into 2 doses. It is recommended to regularly conduct glycemic control to assess the need for further use of the drug.

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.

Patients with creatinine clearance 45-59 ml/min: the initial dose is 500 mg or 850 mg once daily. The maximum dose is 1000 mg per day, divided into 2 doses. Renal function should be carefully monitored every 3-6 months. If creatinine clearance is below 45 ml/min, the drug should be discontinued immediately.

Elderly patients

Storage conditions

Store out of the reach of children at a temperature not exceeding 25°C.

Best before date

3 years. Do not use after the expiration date stated on the package.

special instructions

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 patients with diabetes mellitus and 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 acidotic shortness of breath, abdominal pain and hypothermia followed by coma.

Diagnostic laboratory parameters are a decrease in blood pH (less than 7.25), lactate content in the blood plasma over 5 mmol/l, increased anion gap and lactate/pyruvate ratio. If metabolic 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 creatinine clearance:

at least once a year in patients with normal renal function;
at least 2-4 times a year in elderly patients, as well as in patients with creatinine clearance 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 non-steroidal anti-inflammatory drugs.

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 heart failure with unstable hemodynamic parameters is contraindicated.

Children and teenagers

The diagnosis of type 2 diabetes mellitus must be confirmed before starting treatment with metformin.

In clinical studies lasting 1 year, metformin was shown to have no effect on growth and puberty. 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.

Clinical experience with metformin in children aged 10 to 12 years is limited, so the most careful monitoring is necessary in children in this age group.

Other precautions:

Patients are advised to continue to follow a diet with even carbohydrate intake throughout the day. Overweight patients are advised to continue to follow a low-calorie diet (but not less than 1000 kcal/day).
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 hypoglycemic agents (for example, sulfonylureas, repaglinide, etc.).

Symptoms of hypoglycemia include weakness, headache, dizziness, excessive sweating, tachycardia, visual disturbances, and difficulty concentrating. The use of the drug in patients with prediabetes is recommended in the presence of additional risk factors for the development of overt type 2 diabetes mellitus, which include: age less than 60 years, body mass index >30 kg/m2, history of gestational diabetes mellitus, family history of diabetes mellitus in first-degree relatives line of kinship, increased triglyceride concentrations, decreased HDL cholesterol concentrations, arterial hypertension.

Effect on fertility

Metformin did not affect fertility in male or female rats when administered at doses three times the maximum recommended daily dose for humans.

The film shell contains lactose monohydrate, so the drug is contraindicated in patients with lactose intolerance, lactase deficiency, and glucose-galactose malabsorption.

Description

Oral hypoglycemic drug.

Dosage form

White or almost white, film-coated tablets, oblong, biconvex, scored on both sides.

Use in children

The drug should be used with caution in children aged 10 to 12 years.

Pharmacodynamics

The drug Metformin-Richter reduces hyperglycemia without leading to the development of hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and does not have a hypoglycemic effect in healthy individuals. 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, delaying 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.

In addition, it has a beneficial effect on lipid metabolism: it reduces the content of total cholesterol, LDL and triglycerides.

While taking metformin, the patient's body weight either remains stable or decreases moderately.

Clinical studies have also shown the effectiveness of metformin for the prevention of diabetes mellitus in patients with prediabetes with additional risk factors for the development of overt type 2 diabetes mellitus in whom lifestyle changes have not achieved adequate glycemic control.

Side effects

Determination of the frequency of side effects: 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).

Side effects are presented in order of decreasing importance.

Metabolic 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.

From the nervous system: often - taste disturbance.

From the digestive system: 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 resolve spontaneously. To prevent symptoms, it is recommended to take metformin 2 or 3 times a day during or after meals. Slowly increasing the dose may improve gastrointestinal tolerability.

From the skin and subcutaneous tissues: very rarely - skin reactions such as erythema, itching, rash.

From the liver and biliary tract: very rarely - impaired liver function tests and hepatitis; after discontinuation of metformin, these adverse effects completely disappear.

Published data, post-marketing data, and controlled clinical studies in limited pediatric populations aged 10-16 years indicate that adverse effects in children are similar in nature and severity to those in adult patients.

Use during pregnancy and breastfeeding

Pregnancy
The use of Metformin-Richter during pregnancy is contraindicated.

Decompensated diabetes mellitus during pregnancy is associated with an increased risk of birth defects and perinatal mortality. Limited evidence suggests that taking metformin in pregnant women does not increase the risk of birth defects in their children.

When planning pregnancy, as well as in the event of pregnancy while taking metformin for prediabetes and type 2 diabetes mellitus, the drug should be discontinued, and insulin therapy should be prescribed in case of type 2 diabetes mellitus. It is necessary to maintain the glucose level in the blood plasma at a level closest to normal to reduce the risk of fetal malformations.

Breast-feeding

Metformin passes into 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 for the baby.

Interaction

Contraindicated combinations

Iodinated contrast agents: against the background of functional renal failure in patients with diabetes mellitus, radiological examination using iodinated contrast agents can cause the development of lactic acidosis. Treatment with Metformin-Richter should be discontinued depending on renal function 48 hours before or during an X-ray examination using iodinated contrast agents and not resumed 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

Danazol: simultaneous use of danazol is not recommended to avoid the hyperglycemic effect of the latter. If treatment with danazol is necessary and after stopping the latter, a dose adjustment of Metformin-Richter is required under the control of blood glucose concentrations.

Chlorpromazine: when taken in high doses (100 mg/day), it increases the concentration of glucose in the blood, reducing the release of insulin. When treated with antipsychotics and after stopping the latter, dose adjustment of the drug is required under the control of blood glucose concentrations.

GCS of systemic and local action reduce glucose tolerance, increase the concentration of glucose in the blood, sometimes causing ketosis. When treating GCS and after stopping the latter, dose adjustment of Metformin-Richter is required under the control of blood glucose concentrations.

Diuretics: Concomitant use of loop diuretics may lead to the development of lactic acidosis due to possible functional renal failure. Metformin-Richter should not be prescribed if CC is below 60 ml/min.

Beta2-adrenergic agonists prescribed by injection increase blood glucose concentrations due to stimulation of beta2-adrenergic receptors. In this case, monitoring of blood glucose concentration is necessary. If necessary, insulin administration is recommended. When using the above drugs simultaneously, more frequent monitoring of blood glucose may be required, especially at the beginning of treatment. If necessary, the dose of metformin can be adjusted during treatment and after its cessation.

Antihypertensive drugs, with the exception of ACE inhibitors, can reduce blood glucose concentrations. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of Metformin-Richter 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.

The hypoglycemic effect of metformin can be reduced by phenothiazides, glucagon, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, isoniazid, slow calcium channel blockers, levothyroxine sodium.

Concomitant use with cimetidine reduces the rate of elimination of metformin, which can lead to the development of lactic acidosis.

In healthy volunteers, with simultaneous use of metformin and propranolol, as well as with the use of metformin and ibuprofen, no changes in their pharmacokinetic parameters were observed.

Metformin may reduce the effect of indirect anticoagulants.

Organic cation transporter substrates 1 and 2 (OST1 and OST2)

Metformin is a substrate of the organic cations OCT1 and OCT2.

When used together with metformin:

OCT1 inhibitors (such as verapamil) may reduce the hypoglycemic effect of metformin;
OCT1 inducers (such as rifampicin) can increase the absorption of metformin in the gastrointestinal tract and enhance its hypoglycemic effect;
OCT2 inhibitors (such as cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may reduce the renal excretion of metformin and lead to an increase in its plasma concentration.

OCT1 and OCT2 inhibitors (such as crizotinib, olaparide) may reduce the hypoglycemic effect of metformin.

Overdose

Symptoms: 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. Significant overdose or associated risk factors can lead to the development of lactic acidosis (see section "Special instructions").

Treatment: if signs of lactic acidosis appear, treatment with the drug must be stopped immediately, the patient must be urgently hospitalized and, having determined 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.

Impact on the ability to drive vehicles and operate machinery

Monotherapy with Metformin-Richter does not cause hypoglycemia, and therefore does not affect the ability to drive vehicles and machines. However, patients should be warned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylureas, insulin, repaglinide, etc.).