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

tablet shell - Defect (White) OY-S-7257 (hypromellose-5cP-2.72 mg, titanium dioxide-2.46 mg, hypromellose-15cP-1.36 mg, hypromellose-50cP-0.82 mg, macrogol-400-0.64 mg), about 8 mg .

1 tablet, film-coated, 850 mg contains:

active substance: metformin hydrochloride 850.00 mg;

Excipients: povidone-K25 - 51.00 mg, stearic acid - 9.18 mg, silicon colloidal dioxide - 4.37 mg;

tablet shell - Defect (White) OY-S-7257 (hypromellose-5cP-6.12 mg, titanium dioxide-5.54 mg, hypromellose-15cP-3.06 mg, hypromellose-50cP-1.84 mg, macrogol-400-1.44 mg), about 18 mg .

1 tablet, film-coated, 1000 mg contains:

active substance: metformin hydrochloride - 1000.00 mg;

Excipients: povidone-K25 - 60.00 mg, stearic acid - 10.80 mg, silicon dioxide colloid - 5.14 mg;

tablet shell - Defect (White) OY-S-7257 (hypromellose-5cP-7.14 mg, titanium dioxide-6.47 mg, hypromellose-15cP-3.57 mg, hypromellose-50cP-2.14 mg, macrogol-400-1.68 mg), about 21 mg.

Description:

Tablets 500 mg:

Round, biconvex tablets, film-coated, white, engraved "MF"on one side.

Tablets 850 mg:

Round, biconvex tablets, film-coated, white, engraved "MN" on one side.

Tablets 1000 mg:

Oval, biconvex tablets covered with a film membrane, white with a risk on one side and engravings "M" and "T" on opposite sides of the risks.

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

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

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 the metabolism of lipids: reduces the concentration 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:

After ingestion metformin absorbed from the gastrointestinal tract quite fully. Absolute bioavailability is 50-60%. The maximum concentration (C_m_Oh) (approximately 2 μg / ml or 15 μmol) in blood plasma is achieved after 2.5 hours. With simultaneous intake of food, the absorption of metformin is reduced and delayed.

Metformin is rapidly distributed into tissues, practically does not bind to blood plasma proteins. 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 (CC)), 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;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or renal dysfunction (CC less than 60 ml / min);

- acute conditions that occur with the risk of developing renal dysfunction: a decrease in the total volume of circulating blood (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 cardiac or respiratory failure, acute myocardial infarction);

- extensive surgery and trauma, when insulin therapy is indicated (see section "Special instructions");

- hepatic failure, a violation of liver function;

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactoacidosis (including in the anamnesis);

- application for less than 48 hours before and within 48 hours after radioisotope or radiographic studies with administration iodine-containing contrast medium (see section "Interaction with other medicinal products");

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

- children's age until 10 years.

Carefully:

- Patients over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis;

- the period of breastfeeding.

Pregnancy and lactation:

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

When planning pregnancy, as well as 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 is excreted in breast milk. Side effects of newborns with breastfeeding against 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 made 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 a sufficient amount of water (approximately a glass, about 200-250 ml).

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. A further gradual increase in the dose is possible depending on the concentration of glucose in the blood.

- 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.

- A slow increase in dosage can help improve gastrointestinal tolerance.

- Patients receiving metformin in doses of 2000-3000 mg / day, can be transferred to receive the drug Diafor 1000 mg. The maximum recommended dose is 3000 mg / day, divided into 3 doses.

In case of planning a transition from taking another hypoglycemic agent: it is necessary to stop taking another remedy and start taking Diazfor 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 the drug DiaSpor 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.

Elderly patients

Because of the possible decrease in renal function, the dose of metformin should be selected under regular monitoring of renal function (to determine the concentration of serum creatinine at least 2-4 times a year).

Children and teenagers from 10 to 18 years

In children from 10 years of age, Diazfor can be used both in monotherapy and in combination with insulin.

The usual initial dose is 500 mg or 850 mg once a day after or during a meal. 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.

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.

Side effects:

The frequency of side effects of metformin is distributed as follows:

Very often: ≥ 1/10; often: ≥ 1/100, <1/10; infrequently: ≥ 1/1000, <1/100; rarely: ≥ 1/10 000, <1/1000; very rarely: <1/10 000; frequency is unknown (can not be estimated from available data).

Side effects are presented in order of decreasing importance.

Disorders from the metabolism and nutrition:

Very rarely: lactic acidosis (see section "Special instructions").

With prolonged use of metformin, a decrease in the 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 violation of taste.

Disorders from the gastrointestinal tract:

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 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.

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 (see section "Special instructions").

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 metformin should be canceled depending on the function of the kidneys 48 hours before or during the X-ray examination using iodine-containing radiopaque means and not to resume earlier 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 developing lactic acidosis, especially in the case of:

- malnutrition, low-calorie diet;

- liver failure.

During taking the drug should avoid drinking alcohol and drugs containing ethanol.

Combinations that require caution

Danazol: It is not recommended to take danazol concurrently to avoid hyperglycemic action of the latter. If it is necessary to treat danazol and after stopping the reception of the latter, correction of the dose of metformin is required under the control of the concentration of glucose in the blood.

Chlorpromazine: when taken in high doses (100 mg per day) increases the concentration of glucose in the blood, reducing the release of insulin. When treating with neuroleptics and after stopping the intake of the latter, correction of the dose of the drug 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 the latter, correction of the dose of metformin is required under the control of the concentration of glucose 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 SC 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 blood glucose concentration 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 reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of metformin with 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 over the tubular transport systems and can lead to an increase in its C_mOh.

Special instructions:

Lactic acidosis

Lactic acidosis is a rare, but serious (high mortality in the absence of emergency treatment) complication, which can 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

Diafor should be discontinued 48 hours before planned surgical procedures and can be continued no earlier than 48 hours after, provided that during the examination the renal function was recognized as 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.

Children and teens

Diagnosis of Type 2 diabetes mellitus should be confirmed before treatment with Diafor. 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:

Monotherapy with Diazfor does not cause hypoglycemia, so it does not affect the ability to drive vehicles and mechanisms.

Nevertheless, patients should be cautioned about the risk of developing hypoglycemia when using Diazfor in combination with other hypoglycemic drugs (sulfonylureas, repaglinide, insulin), in which the ability to drive vehicles and engage in other potentially hazardous activities that require increased attention and speed psychomotor reactions.

Form release / dosage:Film-coated tablets, 500 mg, 850 mg, 1000 mg.

Packaging:

For 10 tablets in a PVC / A1 blister.

By 2, 3, 4, 5, 6, 9, 10 or 18 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003547

Date of registration:01.04.2016

Date of cancellation:2021-04-01

The owner of the registration certificate:Actavis PTS ehf GroupActavis PTS ehf Group Iceland

Manufacturer: & nbsp

IPCA LABORATORIES, Ltd. India

BALKANPHARMA-DUPNITSA, AD Bulgaria

Representation: & nbspAktavis, Open Company Aktavis, Open Company

Information update date: & nbsp13.06.2016

Illustrated instructions

Instructions

Diafor (Diasfor)