Siofor 850 - instructions for use, dose, side effects, contraindications

Metformin belongs to the biguanide group. Has hypoglycemic action. Provides a reduction in both basal and postprandial glucose concentrations in blood plasma. Does not stimulate the secretion of insulin and therefore does not lead to hypoglycemia.

The action of metformin is based on the following mechanisms:

- decrease in glucose production in the liver due to suppression of gluconeogenesis and glycogenolysis;

- increased sensitivity of muscles to insulin and, consequently, improved absorption and utilization of glucose at the periphery;

- oppression of glucose absorption in the intestine.

Metformin by action on glycogen synthase stimulates intracellular synthesis of glycogen. Increases the transport capacity of all known to date membrane transport proteins of glucose.

Has, regardless of its effect on the concentration of glucose in the blood plasma, a favorable effect on lipid metabolism, leads to a decrease in the concentration of total cholesterol, low-density lipoprotein cholesterol and triglycerides.

Against the background of the use of metformin in patients with diabetes mellitus, the body weight either remains stable or moderately decreases.

Pharmacokinetics:

Suction

After taking the drug inside, metformin Absorbed almost completely from the gastrointestinal tract, the maximum concentration (C_m_Oh) in the blood plasma is achieved after 2.5 hours and at the maximum dose does not exceed 4 μg / ml.Eating reduces the degree of absorption (C_m_Oh decreases by 40%, the area under the curve "concentration-time" (AUC) by 25%) and slightly slows the absorption of metformin from the gastrointestinal tract (time to reach C_m_Oh decreases by 35 minutes). When used in recommended doses, the equilibrium concentration in blood plasma is reached within 24-48 hours and, as a rule, does not exceed 1 μg / ml. Absolute bioavailability in healthy volunteers is approximately 50 - 60%.

Distribution

Virtually does not bind to blood plasma proteins. Penetrates into red blood cells. FROM_m_Oh in the blood below C_m_Oh in blood plasma and achieved approximately the same time. Probably, red blood cells are a secondary distribution compartment. Average volume of distribution (V_d) is 63-276 liters.

Metabolism and excretion

It is excreted by the kidneys unchanged. Metabolites in the human body is not found. Kidney clearance is> 400 ml / min. Half-life (T1/2) is about 6.5 hours. With a decrease in kidney function, the clearance of metformin decreases in proportion to the clearance of creatinine, respectively, the half-life is prolonged and the concentration of metformin in the blood plasma is increased.

Children

With a single application of metformin in children at a dose of 500 mg, the pharmacokinetic parameters were similar to those in adults.

Indications:

Diabetes mellitus type 2, especially in patients with excessive body weight, to control the concentration of glucose in the blood plasma.

- in adults as a monotherapy or as part of a combination therapy with other oral hypoglycemic agents and / or insulin.

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

Treatment of type 2 diabetes should be accompanied by dietary correction and increased physical activity (in the absence of contraindications).

Contraindications:

- hypersensitivity to metformin or excipients of the drug;

- diabetic ketoacidosis, diabetic precoma, coma;

- impaired renal function (creatinine clearance <60 ml / min);

- acute conditions that occur with the risk of developing renal dysfunction: dehydration (eg, with diarrhea, vomiting), severe infectious diseases, shock;

- acute or chronic conditions accompanied by tissue hypoxia (cardiac or respiratory failure, recent myocardial infarction, shock);

- period for 48 hours before the beginning and 48 hours after radioisotope or radiographic studies with the introduction of iodine-containing radiopaque (in angiography or urography) (intravenous administration of iodine-containing radiocontrast agents may lead to impaired renal function);

- period for 48 hours before the beginning and 48 hours after the surgical interventions;

- hepatic failure, impaired liver function;

- lactoacidosis (including, in the anamnesis);

- acute alcohol intoxication, chronic alcoholism;

- adherence to low-calorie diet (less than 1000 kcal per day);

- children's age till 10 years;

- pregnancy.

Carefully:

- children age from 10 to 12 years;

- the period of breastfeeding;

- people over 60 years old who perform heavy physical work (increased risk of lactic acidosis).

Pregnancy and lactation:

Uncontrolled diabetes mellitus during pregnancy can lead to an increased risk of congenital anomalies and perinatal mortality. A limited amount of evidence suggests that the use of metformin in pregnant women does not increase the risk of congenital malformations in children.

Data from animal studies have not shown any adverse effects on pregnancy, embryonic fetal development, delivery, or postnatal development.

When planning pregnancy with diabetes, as well as in case of its onset, it is recommended to use insulin to maintain blood glucose concentration at the level closest to normal values, in order to reduce the risk of developing fetal malformations.

A patient with diabetes should be warned about the need to inform the doctor in case of pregnancy.

Metformin penetrates into breast milk. Infants / infants who are breastfed, whose mothers receive metformin, no negative effects of metformin were observed. However, given the limited data, the use of metformin is not recommended for women during breastfeeding. The decision to stop breastfeeding should be made in consideration of the benefits of breastfeeding and the potential risk of adverse reactions in the child.

Dosing and Administration:

Inside.

The dose and dosage regimen of the drug, as well as the duration of treatment, are determined by the attending physician depending on the concentration of glucose in the blood plasma.

Adults

Monotherapy or as part of combination therapy with other hypoglycemic agents for oral administration

The recommended initial dose is 850 mg (1 tablet of Siofor® 850) 2-3 times daily during or after meals.

In 10-15 days after the beginning of taking the drug, a further gradual increase in the dose is possible depending on the concentration of glucose in the blood plasma to an average daily dose of 2-3 tablets of the preparation Siofor 850. The gradual increase in the dose improves the tolerance of the drug on the part of the gastrointestinal tract.

The maximum dose of metformin is 3000 mg per day in 3 divided doses.

If the patient is transferred to Siofor 850 for treatment with other hypoglycemic drugs, stop taking the drug and start taking Siofor 850 at the above doses.

Simultaneous use with insulin

The preparation Siofor® 850 and insulin can be combined to improve glycemic control.The standard initial dose is 850 mg (1 tablet of Siofor® 850) 2-3 times a day, with a gradual increase in the dose with an interval of approximately one week to an average daily dose of 2-3 tablets; The insulin dose is determined based on the concentration of glucose in the blood plasma.

The maximum dose of metformin is 3000 mg per day in 3 divided doses.

Elderly patients

Due to possible renal dysfunction in elderly patients, the dose of Siofor® 850 is selected taking into account the concentration of creatinine in the blood plasma. A regular assessment of the functional state of the kidneys is necessary.

Children from 10 to 18 years old

Monotherapy and simultaneous use with insulin

The standard initial dose is 850 mg (1 tablet of Siofor® 850) once a day during or after a meal.

In 10-15 days after the beginning of taking the drug, a further gradual increase in the dose is possible depending on the concentration of glucose in the blood plasma. The gradual increase in the dose improves the tolerance of the drug from the side of the gastrointestinal tract.

The maximum dose of metformin for children is 2000 mg per day in 2 to 3 doses.

With simultaneous use with insulin, the dose of insulin is determined based on the concentration of glucose in the blood plasma.

Side effects:

Possible side effects when using the drug are given below in accordance with the classification of the World Health Organization in the descending frequency of occurrence: very often (≥1 / 10); often (≥1 / 100, <1/10), infrequently (≥1 / 1000, <1/100), rarely (≥1 / 10000, <1/1000), very rarely (<1/10000), including individual message.

Impaired nervous system:

Often: a taste disorder.

Disorders from the gastrointestinal tract:

Often: nausea, vomiting, diarrhea, abdominal pain, loss of appetite.

These adverse events often occur at the beginning of therapy and in most cases are spontaneous. To prevent symptoms, the dose of the drug is recommended to be divided into 2-3 meals during or after a meal. The gradual increase in the dose improves the tolerance of the drug from the side of the gastrointestinal tract.

Disturbances from the skin and subcutaneous tissues:

Rarely: skin reactions, for example, erythema, pruritus, rash.

Disorders from the metabolism and nutrition:

Rarely: lactoacidosis (requires discontinuation of treatment). Symptoms of lactic acidosis - see the section "Overdose".

With prolonged use there is a decrease in absorption of vitamin B12 and a decrease in its concentration in the blood plasma. This should be taken into account if the patient has megaloblastic anemia.

Disorders from the liver and bile ducts:

Rarely: reversible violations of liver function, expressed in an increase in the activity of hepatic transaminases, or hepatitis, which occur after discontinuation of metformin.

Children:

According to the data obtained during post-registration use and the results of controlled clinical trials, when metformin was used for 1 year in children aged 10-16 years, the incidence and severity of side effects were comparable to those of adults.

Overdose:

When metformin was used in doses up to 85 g, hypoglycemia was not observed.

If there is a significant overdose, lactoacidosis may develop, with severe weakness, respiratory disorders, drowsiness, nausea, vomiting, diarrhea, abdominal pain, hypothermia, lowering of blood pressure, reflex bradyarrhythmia. Muscle cramps, confusion and loss of consciousness can be noted. If suspected of developing lactic acidosis, immediate discontinuation of the drug and emergency hospitalization are recommended.

The most effective method of removing lactate and metformin from the body is hemodialysis.

Interaction:

Simultaneous use is contraindicated

Iodine-containing radiopaque agents

Intravascular injection of iodine-containing radiocontrast agents in patients with diabetes mellitus can be complicated by renal insufficiency, metformin cumulates and increases the risk of developing lactic acidosis. The use of Siofor 850 should be discontinued within 48 hours before and not resumed earlier than 48 hours after the X-ray examination using iodine-containing radiopaque agents with normal serum creatinine concentration.

Simultaneous use is not recommended

Alcohol and ethanol containing preparations

The risk of developing lactic acidosis increases with acute alcohol intoxication or simultaneous use with ethanol-containing drugs, especially against fasting or eating disorders, as well as liver failure. When taking metformin, avoid taking alcohol and medications containing ethanol.

Simultaneous use requires caution

The simultaneous use of metformin with danazol can lead to the development of a hyperglycemic effect.If it is necessary to treat danazol and after discontinuing its use, correction of the dose of metformin is required under the control of the glucose concentration in the blood plasma.

Chlorpromazine: when used in high doses (100 mg per day) increases the concentration of glucose in the blood plasma, reducing the release of insulin. When treating with neuroleptics and after stopping the application of the latter, correction of the dose of metformin is required under the control of the glucose concentration in the blood plasma.

When used simultaneously with oral contraceptives, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, nicotinic acid it is possible to increase the concentration of glucose in the blood plasma. Nifedipine increases absorption, the maximum concentration of metformin in the blood plasma, prolongs its excretion.

Cationic preparations (amiloride, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, vancomycin) secreted in tubules, compete for tubular transport systems and with prolonged therapy can increase the maximum concentration of metformin in the blood plasma. Metformin reduces the maximum concentration and half-life furosemide; can weaken the effect anticoagulants of indirect action.

Glucocorticoids (systemic and topical application), beta2-adrenomimetics (in the form of injections) have hyperglycemic activity. It is necessary to more closely monitor the concentration of glucose in the blood plasma, especially at the beginning of treatment. If necessary, the dose of metformin should be adjusted for the period of simultaneous use, as well as after the withdrawal of these drugs.

With simultaneous use with diuretics, especially "loop", there may be an increased risk of developing lactic acidosis, due to the potential ability of diuretics to reduce kidney function.

ACE inhibitors and other antihypertensive drugs can reduce the concentration of glucose in the blood plasma. If necessary, the dose of metformin can be adjusted.

Substrates of the conveyor of organic cations 2 (OCT2)

With simultaneous application ranolazine 500 mg and 1000 mg twice a day and metformin 1000 mg twice a day, the concentration of metformin in the blood plasma in patients with type 2 diabetes increases 1.4 and 1.8 times, respectively.

With simultaneous application of 400 mg cimetidine two times a day in 7 healthy volunteers AUC and C_ma_x metformin increased by 50% and 81%, respectively. With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose, salicylates possibly increased hypoglycemia.

Special instructions:

Lactic acidosis is a serious pathological condition, which is extremely rare, associated with the accumulation of lactate in the blood, which can be caused by the cumulation of metformin (symptoms of lactic acidosis - see the section "Overdose"). Diagnostic laboratory indicators of lactic acidosis 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. The described cases of lactic acidosis in patients who received metformin, were observed mainly in patients with diabetes mellitus with severe renal failure. Prevention of lactic acidosis involves the identification of all associated risk factors, such as decompensated diabetes mellitus, ketosis, prolonged fasting, excessive alcohol consumption, liver failure and any condition associated with hypoxia.If suspected of developing lactic acidosis, immediate discontinuation of the drug and emergency hospitalization are recommended.

Because the metformin is excreted by the kidneys, when using the preparation Siofor 850 should regularly monitor the concentration of serum creatinine:

- at least once a year in patients with normal renal function;

- at least 2-4 times a year in patients with a serum creatinine concentration close to the upper limit of the norm, as well as in elderly patients.

Particular care should be taken in cases where there is a risk of impaired renal function, for example, at the beginning of therapy with antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs (NSAIDs).

Treatment with Siofor 850 should be temporarily replaced with other hypoglycemic agents (eg, insulin) for 48 hours before and 48 hours after the X-ray examination with intravenous iodine-containing radiopaque agents.

Use of Siofor 850 should be discontinued within 48 hours prior to a planned surgical operation under general anesthesia, with spinal or epidural anesthesia.Continue therapy should be after the resumption of oral nutrition or no earlier than 48 hours after surgery, subject to confirmation of normal renal function.

The preparation Siofor 850 does not replace the diet and daily exercise - these types of therapy must be combined in accordance with the recommendations of the doctor. During treatment with Siofor 850, all patients should adhere to dietary nutrition with an even intake of carbohydrates throughout the day. Patients with excessive body weight should follow a low-calorie diet.

Standard laboratory tests for patients with diabetes should be carried out regularly.

Before using Siofor 850 in children from 10 to 18 years, it is necessary to confirm the diagnosis of type 2 diabetes.

In controlled clinical trials, 1 year of metformin exposure to growth and development, as well as puberty of children was not observed, data on these indicators for longer-term use are not available. In this regard, careful monitoring of the relevant parameters in children receiving metformin, especially in the prepubertal period (10-12 years).

Monotherapy with Siofor 850 does not lead to hypoglycemia, but caution should be exercised when using the drug together with insulin or sulfonylurea derivatives.

Metformin did not affect the fertility of male or female rats when administered at doses (600 mg / kg / day), three times the maximum recommended daily dose for humans.

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

The use of Siofor 850 does not cause hypoglycemia, so it does not affect the ability to drive vehicles and maintain machinery.

With the simultaneous use of the preparation Siofor 850 with other hypoglycemic drugs (derivatives of sulfonylureas, insulin, repaglinide), it is possible to develop hypoglycemic conditions, so care must be taken when driving vehicles and other potentially dangerous activities that require concentration and speed of psychomotor reactions.

Form release / dosage:Coated tablets, 850 mg.

Packaging:

For 15 tablets in a contour mesh package (blister) [PVC-foil / aluminum foil].

For 2, 4 or 8 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep the medicine out of the reach of children!

Shelf life:3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N013674 / 01

Date of registration:13.04.2012 / 21.10.2015

The owner of the registration certificate:Berlin-Chemie, AGBerlin-Chemie, AG Germany

Manufacturer: & nbsp

BERLIN-CHEMIE, AG Germany

MENARINI-VON HEYDEN, GmbH Germany

Representation: & nbspBERLIN-CHEMI / MENARINI PHARMA GmbH BERLIN-CHEMI / MENARINI PHARMA GmbH Germany

Information update date: & nbsp28.03.2016

Illustrated instructions

Instructions

Siofor® 850 (Siofor® 850)