Gliiformin - instructions for use, dose, side effects, contraindications

Excipients: pregelatinized starch - 22.5 mg; silicon dioxide colloidal - 0,4 mg; Povidone (type K90) - 25 mg, glycerol - 10 mg; crospovidone (type B) - 20 mg; stearic acid - 2.1 mg.

Shell composition: hypromellose-2910 - 16.4 mg, macrogol-6000 - 2 mg, talc - 1.6 mg.

Description:

Oval, biconvex tablets, covered with a film coat of white or white with a yellowish or grayish hue. On the break the tablets are white.

Pharmacotherapeutic group:Hypoglycemic agent for oral administration of the biguanide group

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin is an oral hypoglycemic agent from the biguanide group. Metformin reduces hyperglycemia, without leading to the development of hypoglycemia. Unlike derivatives of sulfonylureas, 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. It inhibits gluconeogenesis in the liver. Delays the absorption of carbohydrates in the intestine. Metformin stimulates the synthesis of glycogen, affecting 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, low-density lipoproteins and triglycerides.

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

Pharmacokinetics:

Absorption and distribution

After oral administration metformin absorbed from the gastrointestinal tract quite fully. Absolute bioavailability is 50-60%. Maximum concentration (FROM_m_Oh) (about 2 mcg / ml or 15 μmol) in plasma is achieved through 2,5 h.With simultaneous intake of food, absorption of metformin is reduced and delayed. Metformin quickly distributed into tissues, practically does not bind to plasma proteins.

Metabolism and excretion

Exposed to a very weak degree of metabolism and excreted by the kidneys. The clearance of metformin in healthy subjects is 400 ml / min (4 times greater than the creatinine clearance), which indicates the presence of active tubular secretion. The half-life is approximately 6.5 hours. With renal insufficiency it increases, there is a risk of cumulation of the drug.

Indications:

Diabetes mellitus type 2, especially in patients with obesity, with ineffectiveness of diet and exercise:

- in adults as a monotherapy or in combination with other oral hypoglycemic agents, or with insulin;

- in children from 10 years as a monotherapy or in combination with insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance of the drug;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or renal dysfunction (creatinine clearance (CK) less than 60 ml / min);

- acute conditions taking place with the 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 hemodynamics, respiratory failure, acute myocardial infarction);

- extensive surgery and trauma, when insulin therapy is indicated;

- hepatic failure, impaired liver function;

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactoacidosis (including in the anamnesis);

- use for less than 48 hours before and within 48 hours after radioisotope or X-ray studies with the introduction of iodine-containing contrast media;

- compliance with a low-calorie diet (less than 1000 kcal / day);

- children under 10 years old.

Carefully:

With caution apply the drug in people over 60 years of age, performing heavy physical work, that is associated with an increased risk of developing lactic acidosis; during the period of breast feeding.

Pregnancy and lactation:

A limited amount of evidence suggests that the use of metformin y pregnant women does not increase the risk of congenital malformations in children.

When planning pregnancy, and also in case of pregnancy on the background of taking metformin, the drug should be canceled, and insulin therapy is prescribed. It is necessary to maintain the level of glucose in the blood plasma at the level closest to the norm in order to reduce the risk of fetal malformations.

Metformin penetrates into breast milk. Undesirable reactions in newborns during breastfeeding with metformin were not observed. However, due to the limited amount of data, the use of the drug during breastfeeding is not recommended. The decision to stop breastfeeding should be taken in consideration of the benefits of breastfeeding and the potential risk of side effects in the child.

Dosing and Administration:

Tablets should be taken orally, swallowed whole, without chewing, during or immediately after eating, with plenty of water.

Adults:

Monotherapy and combination therapy in combination with other oral hypoglycemic agents:

The usual initial 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.

A slow increase in dosage can help improve gastrointestinal tolerance.

The maintenance dose of the drug is usually 1500-2000 mg per 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 per day, divided into 3 doses.

Patients receiving metformin in doses of 2000-3000 mg per day, can be switched to taking a drug metformin in a dosage of 1000 mg. The maximum recommended dose is 3000 mg per day, divided into 3 doses.

In case of planning the transition from taking another hypoglycemic agent: it is necessary to stop taking the other agent and start taking Gliformin® in the dose indicated above.

Combination with insulin

To achieve better control of blood glucose metformin and insulin can be used as a combination therapy.The usual initial dose of Gliformin® is 500 mg or 850 mg * 2-3 times a day, while the insulin dose is selected based on the concentration of glucose in the blood.

Children and adolescents: in children from 10 years of age the preparation Gliiformin can be used both in monotherapy and in combination with insulin.

The usual initial dose is 500 mg or 850 mg * per day after or during meals. After 10-15 days, the dose should be adjusted based on the blood glucose concentration. The maximum daily dose is 2000 mg, divided into 2-3 doses.

Older patients: because of the possible decrease in kidney function, the dose of Gliiformin® should be selected under regular monitoring of renal function (to determine the concentration of serum creatinine at least 2-4 times a year).

Duration of treatment

The duration of treatment is determined by the doctor. It is not recommended to interrupt the use of the drug without the indication of the attending physician.

* If a doctor prescribes an initial dose of 850 mg, a medicinal product containing metformin in the appropriate dosage.

Side effects:

Side effects are classified according to the following frequency of development: very often (≥ 10%), often (≥ 1%, <10%), infrequently (≥ 0.1%, <1%),rarely (≥ 0.01%, <0.1%), very rarely (<0.01%), the incidence is not established (there is currently no evidence of a prevalence of side effects).

Disorders from the metabolism and nutrition: very rarely - lactic acidosis (requires withdrawal of the drug). With prolonged use of metformin, there may be a decrease in absorption of vitamin B₁₂. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

Disturbances from the nervous system: often - a taste disorder (metallic taste in the mouth).

Disorders from the gastrointestinal tract: very often - nausea, vomiting, abdominal pain, lack of appetite, diarrhea, flatulence. These undesirable phenomena most often occur during the initial period of treatment and in most cases spontaneously pass. To prevent symptoms, it is recommended to take metformin 2 or 3 times a day during or after a meal. Slow increase in dose may improve gastrointestinal tolerance.

Disturbances from the skin and subcutaneous tissues: very rarely skin reactions such as erythema, pruritus, rash, hives.

Disturbances from the liver and bile ducts: very rarely - a violation of liver function and hepatitis; after the withdrawal of metformin, these undesirable phenomena completely disappear.

Published data, postmarketing data, as well as controlled clinical trials in a limited child population in the age group 10-16 years show that the side effects of children in nature and severity are similar to those in adult patients.

Overdose:

Symptoms: when metformin was used at a dose of 85 g (42.5 times the maximum daily dose), hypoglycemia was not observed, but lactoacidosis was noted.

A significant overdose of metformin or associated risk factors may lead to the development of lactic acidosis.

Treatment: in the case of the appearance of signs of lactic acidosis, the drug should be discontinued immediately, the patient must be hospitalized and, having determined the concentration of lactate, clarify the diagnosis. The most effective measure for excretion from the body of lactate and metformin is hemodialysis. Conduct also symptomatic treatment.

Interaction:

Contraindicated combinations

Iodine-containing radiopaque agents: on the background of functional renal failure in patients with diabetes mellitus, a radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis. Treatment with Gliiformin® should be discontinued 48 hours before the X-ray examination using iodine-containing radiopaque and resumed no earlier than 48 hours after, provided that during the examination the renal function was found to be normal.

Unrecommended combinations

Alcohol: acute alcohol intoxication increases the risk of lactic acidosis, especially in the case of malnutrition, compliance with a low-calorie diet, as well as with liver failure.

During treatment with the drug should avoid the use of alcohol and drugs containing ethanol.

Combinations that require caution

Danazol: It is not recommended simultaneous reception of danazolum in order to avoid hyperglycemic action of the latter. If it is necessary to treat danazol and after stopping its reception, a correction of the dose of Gliformin® under the control of the concentration of glucose in the blood is required.

Chlorpromazine: when taken in high doses (100 mg per day) increases the concentration of glucose in the blood, reducing the release of insulin. In the treatment of neuroleptics and after discontinuation of their intake, a correction of the dose of Gliiformin® under the control of the concentration of glucose in the blood is required.

Glucocorticosteroids (GCS) systemic and local effects reduce glucose tolerance, increase the concentration of glucose in the blood, sometimes causing ketosis. In the treatment of GCS and after discontinuation of their admission, a dose adjustment of metformin is required under the control of the glucose concentration in the blood.

Diuretics: simultaneous administration of "loop" diuretics can lead to the development of lactic acidosis due to possible functional renal failure. Do not assign metformin, if the clearance of creatinine (CC) is below 60 ml / min.

Assigned in the form of injections beta₂-adrenomimetics: increase the concentration of glucose in the blood due to stimulation of beta₂adrenoreceptors. In this case, it is necessary to monitor the concentration of glucose in the blood. If necessary, the appointment of insulin is recommended.

With the simultaneous use of the above medicines, more frequent monitoring of the glucose level in the blood may be required, especially at the beginning of the treatment.If necessary, the dose of metformin can be adjusted during treatment and after its termination.

Hypotensive drugs, except for angiotensin-converting enzyme inhibitors, can reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of metformin from derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine increases absorption and C_mOh metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin), secreted in the renal tubules, compete with metformin for the tubular transport systems and can increase its FROM_m_Oh.

Special instructions:

Lactic acidosis

Lactic acidosis is a rare but serious (high mortality in the absence of emergency treatment) complication, which may occur due to the cumulation of metformin. The cases of lactic acidosis with the use of metformin occurred, mainly, in patients with diabetes mellitus with severe renal failure.

Other associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia, can help to reduce the incidence of lactic acidosis.

The risk of developing lactic acidosis when nonspecific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe asthenia, should be considered.

Lactic acidosis is characterized by acidotic dyspnea, abdominal pain and hypothermia followed by coma. Diagnostic laboratory indicators are a decrease in blood pH (less than 7.25), a lactate content in the blood plasma above 5 mmol / l, an increased anion gap and a lactate / pyruvate ratio. If you suspect a lactic acidosis, stop taking the medication and consult a doctor immediately.

Surgical operations

The use of metformin should be discontinued 48 hours before scheduled surgical operations and can be continued no earlier than 48 hours after, provided that during the examination the renal function was recognized normal.

Kidney function

Because the metformin it is necessary to determine QC: 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 at the lower border of the norm.

Care should be taken if there is a possible impairment of kidney 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 kidney failure. Patients with chronic heart failure need regular monitoring of heart and kidney function during the administration of metformin. In acute heart failure and chronic heart failure with unstable hemodynamics, metformin is contraindicated.

Children and teens

The diagnosis of Type 2 diabetes mellitus should be confirmed before the start of treatment with metformin.

In clinical studies of 1 year, it was shown that metformin does not affect growth and puberty. However, in view of the lack of long-term data, careful monitoring of the subsequent influence of metformin on these parameters in children, especially during puberty, is recommended.

The most careful control is needed in children aged 10-12 years.

Other Precautions

Patients are encouraged to continue to follow a diet with an even intake of carbohydrates throughout the day. Patients with excessive body weight are encouraged to continue to follow a low-calorie diet (but not less than 1000 kcal / day).

It is recommended that regular laboratory tests be performed on a regular basis to control diabetes mellitus.

Metformin with monotherapy does not cause hypoglycemia, but caution should be exercised when used in combination with insulin or other hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide).

Effect on the ability to drive transp. cf. and fur:

The use of Gliiformin® in monotherapy does not affect the ability to drive vehicles and mechanisms.

When using Gliiformin ® in combination with other hypoglycemic drugs (derivatives of sulfonylurea,repaglinide, insulin) may develop hypoglycemia, which worsens the ability to drive vehicles and engage in other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 500 mg.

Packaging:

For 6 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil.

5 or 10 contour cell packs of 6 tablets, or 3 or 6 contour cell packs of 10 tablets together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003407

Date of registration:13.01.2016

Expiration Date:13.01.2021

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glyformin® (Gliformin®)