Metformin, tablets 500 mg 60 pcs

Pharmacotherapeutic group
Hypoglycemic drug of oral biguanide group

ATC code
A10BA02

Pharmacological action
Metformin reduces hyperglycemia without causing hypoglycemia. Unlike sulfonylurea derivatives, it does not stimulate insulin secretion and has no hypoglycemic effect in healthy individuals. Increases peripheral receptor sensitivity to insulin and glucose utilization by cells. Inhibits gluconeogenesis in the liver. Delays absorption of carbohydrates 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 favorable effect on lipid metabolism: it reduces total cholesterol, low-density lipoproteins and triglycerides. Against the background of taking metformin, the patient’s body weight either remains stable or decreases moderately.

Indications

Type 2 diabetes mellitus, especially in obese patients with ineffectiveness of diet therapy and physical activity: in adults as monotherapy or in combination with other oral hypoglycemic agents, or with insulin; in children from 10 years old as monotherapy or in combination with insulin.

Active ingredient

Metformin

Composition

One 500 mg tablet contains:

the active ingredient: metformin hydrochloride – 500 mg.

Auxiliary substances: microcrystalline cellulose, croscarmellose sodium, purified water, povidone (polyvinylpyrrolidone), magnesium stearate.

How to take, the dosage

Tablets should be taken orally, swallowed whole, without chewing, during or immediately after a meal, with plenty of water. Adults: monotherapy and combined therapy in combination with other oral hypoglycemic agents: The usual starting dose is 500 mg or 850 mg 2-3 times daily after or with a meal. Further gradual increase of the dose depending on the blood glucose concentration is possible. 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 three doses. Slowly increasing the dose may improve gastrointestinal tolerance. Patients taking metformin at doses of 2000-3000 mg/day may be switched to a dose of 1000 mg. The maximum recommended dose is 3000 mg/day divided into 3 doses. In case of planning to switch from another hypoglycemic drug: it is necessary to stop taking another drug and start Metformin at the dose indicated above. Combination with insulin: To achieve better blood glucose control, metformin and insulin can be used as combined therapy. Usual starting dose of Metformin 500 mg or 850 mg is one tablet 2-3 times per day, Metformin 1000 mg – one tablet once a day, while the dose of insulin is adjusted on the basis of blood glucose concentration. Children and adolescents: In children from the age of 10 years, Metformin can be used as monotherapy or in combination with insulin. Usual starting dose is 500 mg or 850 mg once a day after or with a meal. The dose should be adjusted after 10-15 days on the basis of blood glucose concentration. The maximum daily dose is 2000 mg divided into 2-3 doses. Elderly patients: because of possible decrease in renal function, metformin dose should be adjusted under regular monitoring of renal function parameters (determine serum creatinine concentration at least 2-4 times a year). The duration of treatment is determined by the physician. It is not recommended to interrupt the drug without the instructions of the attending physician.

Special Instructions

Lactoacidosis

Lactoacidosis is a rare but serious (high mortality if not treated urgently) complication that can occur due to metformin cumulation. Cases of lactoacidosis when taking metformin have occurred primarily in patients with diabetes mellitus with severe renal insufficiency.

Other associated risk factors such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure, and any condition associated with severe hypoxia should be considered. This may help to reduce the incidence of lactoacidosis. The risk of lactoacidosis should be considered if nonspecific signs such as muscle cramps accompanied by dyspeptic disorders abdominal pain and marked asthenia occur. Lactoacidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia, followed by coma. Diagnostic laboratory indicators are decreased blood pH (less than 725) plasma lactate content over 5 mmol/L elevated anion gap and lactate/pyruvate ratio. If metabolic acidosis is suspected, discontinue the drug and consult a physician immediately.

Surgery

The use of metformin should be discontinued 48 hours before elective surgery and may be continued up to 48 hours after, provided that renal function has been found to be normal during examination.

Kidney function

Because metformin is excreted by the kidneys before treatment and regularly thereafter, creatinine clearance should be determined:

• at least once a year in patients with normal renal function;
• at least 2-4 times a year in elderly patients and in patients with creatinine clearance at the lower limit of normal.

The drug is contraindicated if creatinine clearance is less than 45 ml/min. Particular caution should be exercised if renal function may be impaired in elderly patients with concomitant use of hypotensive 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 regular monitoring of cardiac function and renal function while taking metformin. Metformin administration is contraindicated in heart failure with unstable hemodynamic parameters.

Children and adolescents

The clinical experience with metformin in children aged 10 to 12 years is limited, so close monitoring is necessary in children in this age group. The diagnosis of type 2 diabetes mellitus must be confirmed before starting metformin treatment. In a 1-year clinical trial, metformin has been shown to have no effect on growth and puberty. However, because of the lack of long-term data, it is recommended that metformin’s subsequent effect on these parameters be closely monitored in children, especially during puberty.

Other Precautions

Patients are advised to continue on a diet with an even carbohydrate intake throughout the day. Patients who are overweight are recommended to continue on a hypocaloric diet (but not less than 1000 kcal/day).

It is recommended that regular standard laboratory tests be performed to control diabetes.

Metformin does not cause hypoglycemia during monotherapy; however, caution is recommended when it is used in combination with insulin or other hypoglycemic agents (such as sulfonylurea derivatives repaglinide, etc.).

The use of the drug in patients with prediabetes is recommended in the presence of additional risk factors for the development of apparent type 2 diabetes, which include:

• age less than 60 years;
• body mass index (BMI) >30 kg/m²;
• gestational diabetes mellitus history;
• high triglyceride concentration;
• decreased HDL cholesterol concentration;
• 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.

The effect on the ability to drive a trans:

Monotherapy with the drug does not cause hypoglycemia so does not affect the ability to operate vehicles and machinery. Patients should be cautioned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic agents (sulfonylurea derivatives repaglinide insulin, etc.) which impairs the ability to drive vehicles and engage in other potentially hazardous activities that require increased attention and quick psychomotor reactions.

Contraindications

Hypersensitivity to metformin or any excipient; diabetic ketoacidosis, diabetic precoma, coma; renal failure or impaired renal function (creatinine clearance (CK) less than 60 ml/min); acute conditions with risk of renal impairment: dehydration (in diarrhea, vomiting), severe infectious diseases, shock; clinically pronounced manifestations of acute or chronic diseases that may lead to the development of tissue hypoxia (including heart or respiratory failure, acute myocardial infarction); Extensive surgery and trauma, when insulin therapy is indicated; hepatic insufficiency, liver dysfunction; chronic alcoholism, acute alcohol poisoning; pregnancy; lactoacidosis (includingincluding in anamnesis); use within less than 48 hours before and within 48 hours after radioisotopic or radiological studies with iodine contrast agent administration; observance of low-calorie diet (less than 1000 kcal/day); children under 10 years old.

Side effects

The frequency of side effects of the drug is rated as follows: very frequently: > 1/10; frequently: 1/10-1/100; infrequently: 1/100-1/1000; rarely: 1/1000-1/10000; very rarely: < 1/10000.

Disorders of metabolism and nutrition

Very rare: lactoacidosis (see section “Special Indications”).

Long-term administration of metformin may result in decreased absorption of vitamin B₁₂. If megaloblastic anemia is detected, the possibility of this etiology should be considered.

Nervous system disorders

Often: impaired taste.

Gastrointestinal tract disorders

Very common: nausea vomiting diarrhea lack of appetite abdominal pain.

These side effects often occur during the initial period of treatment and in most cases go away spontaneously when continued. To reduce side effects, it is recommended that the drug be taken with or after meals. Slowly increasing the dose may improve gastrointestinal tolerance.

Hepatic and biliary tract disorders

Very rare: impaired liver function and hepatitis. After withdrawal of metformin, these adverse events disappear completely.

Skin and subcutaneous tissue disorders

Very rare: skin reactions such as erythema pruritus rash.

Published post-marketing data as well as controlled clinical studies in a limited pediatric population in the 10-16 year age group show that side effects in children are similar in nature and severity to those in adult patients.

Similarities

Siofor 500, Siofor 850, Metformin-Teva, Siofor 1000, Glucofage Long, Formetin, Metformin, Merifatin