Siofor 500, pills 500mg, 60pcs

Composition

Active ingredients:

metformin hydrochloride 500 mg.

Auxiliary substances:

hypromellose – 17.6 mg,

povidone-26.5 mg,

magnesium stearate-2.9 mg.

Shell composition:

hypromellose – 6.5 mg,

macrogol 6000-1.3 mg,

titanium dioxide (E 171) – 5.2 mg

Pharmacological action

Pharmacodynamics

Hypoglycemic drug from the biguanide group. It reduces both basal and postprandial blood glucose concentrations. It does not stimulate insulin secretion and therefore does not lead to hypoglycemia. The effect of metformin is probably based on the following mechanisms: :

• reduced glucose production in the liver due to inhibition of gluconeogenesis and glycogenolysis;
• increased muscle sensitivity to insulin and, consequently, improved peripheral glucose uptake and utilization;
• inhibition of intestinal glucose absorption.

Metformin, through its action on glycogen synthetase, stimulates intracellular glycogen synthesis. Increases the transport capacity of all known glucose membrane transport proteins.

Regardless of its effect on blood glucose levels, it has a beneficial effect on lipid metabolism, leads to a decrease in total cholesterol, low-density cholesterol and triglycerides.

Pharmacokinetics

Suction

After oral use, Cmax in blood plasma is reached in about 2.5 hours and at a maximum dosage does not exceed 4 mcg/ml. With food intake, absorption decreases and slows down slightly. Absolute bioavailability in healthy patients is approximately 50-60%.

Distribution

Practically does not bind to plasma proteins. The average Vd is 63-276 liters. It accumulates in the salivary glands, muscles, liver and kidneys. Penetrates red blood cells.

Deduction

It is excreted unchanged by the kidneys. Renal clearance is >400 ml / min. T1 / 2 is about 6.5 h. >

Pharmacokinetics in special clinical cases

When renal function decreases, metformin clearance decreases in proportion to creatinine clearance. Thus, T1 / 2 lengthens and the concentration of metformin in plasma increases.

Indications

Type 2 diabetes mellitus, especially in overweight patients with ineffective diet therapy and physical activity.

It can be used as monotherapy or in combination with other oral hypoglycemic drugs and insulin.

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

The patient should be warned about the need to inform the doctor in case of pregnancy. When planning or starting pregnancy in a patient with type 2 diabetes mellitus, the drug should be discontinued, with the help of insulin therapy, the blood glucose level should be normalized or as close as possible to normal in order to reduce the risk of fetal defects due to the pathological effects of hyperglycemia.

Metformin penetrates into the milk of laboratory animals. Similar data for humans are not available, so a decision should be made to stop breastfeeding or to discontinue Siofor®, taking into account the need for the drug to be used in the mother.

Contraindications

• Hypersensitivity to Metformin or other components of the drug;
• diabetic ketoacidosis, diabetic precoma;
• renal failure or impaired renal function (CC < 60 ml/min);
• acute conditions that could have a negative impact on renal function (eg, dehydration, severe infection);
• intravascular use of iodinated contrast agents;
• acute or chronic disease can cause tissue hypoxia (e. g., cardiac or respiratory failure, recent myocardial infarction, shock);
• hepatic impairment;
• lactic acidosis (including history);
• pregnancy and lactation (breastfeeding);
• acute alcohol intoxication, chronic alcoholism;
• adherence to a low-calorie diet (less than 1000 kcal/day);
• children up to age 10 years.

With caution: the drug should be used in children aged 10 to 12 years; in patients over 60 years of age who perform heavy physical work, which is associated with an increased risk of developing lactic acidosis.

Side effects

Possible side effects when using the drug are given depending on the frequency of occurrence:

• common (≥1/100, < 1/10);
• uncommon (≥1/1000, < 1/100);
• rare (≥1/10 000, < 1/1000);
• very rare (

From the nervous system: often-a violation of taste.

From the digestive system: nausea, vomiting, “metallic” taste in the mouth, lack of appetite, diarrhea, abdominal pain. These adverse events often occur at the beginning of therapy and in most cases go away spontaneously. To prevent the appearance of symptoms, the dose of the drug is recommended to be distributed in 2-3 doses during or after meals. Gradually increasing the dose reduces the likelihood of undesirable effects from the gastrointestinal tract.

Allergic reactions: very rarely – skin reactions (for example, hyperemia, pruritus, urticaria).

Metabolic disorders: very rare: – lactic acidosis (requires discontinuation of treatment). With prolonged use, there is a decrease in the absorption of vitamin B12 and a decrease in its concentration in blood plasma. This should be considered if the patient has megaloblastic anemia.

From the liver and biliary tract: some reports – reversible liver function disorders, expressed in increased activity of hepatic transaminases, or hepatitis, passing after discontinuation of metformin.

Interaction

Contraindicated combinations

Intravascular use of iodine-containing contrast agents in patients with diabetes mellitus may be complicated by renal failure, as a result of which metformin accumulates and the risk of lactic acidosis increases. The use of Siofor® should be discontinued 48 hours before the procedure and not resumed earlier than 2 days after the X-ray examination using iodine-containing contrast agents, provided that the serum creatinine concentration is normal.

Not recommended combinations

The risk of lactic acidosis increases with acute alcohol intoxication or concomitant use with ethanol-containing drugs, especially against the background of dieting or eating disorders, as well as liver failure.

Combinations that require caution

Concomitant use of metformin with danazol may lead to the development of a hyperglycemic effect. If treatment with danazol is necessary and after discontinuation of its use, it is necessary to adjust the dose of metformin under the control of blood glucose concentration.

When used concomitantly with oral contraceptives, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, nicotinic acid, it is possible to increase the concentration of glucose in the blood.

Nifedipine increases the absorption, Cmax in blood plasma of metformin, prolongs its elimination.

Cationic drugs (amiloride, morphine, procainamide, quinidine, ranitidine, triamterene, vancomycin) secreted in the tubules compete for tubular transport systems and can increase the Cmax of metformin in blood plasma with prolonged therapy.

Cimetidine slows down the elimination of the drug, which increases the risk of lactic acidosis.

Metformin reduces the Cmax and T 1/2 of furosemide.

Metformin may weaken the effect of indirect anticoagulants.

Glucocorticoids (for systemic and topical use), beta-adrenomimetics and diuretics have hyperglycemic activity. Blood glucose levels should be monitored more carefully, especially at the beginning of treatment. If necessary, the dose of metformin should be adjusted for the period of simultaneous use and after discontinuation of these drugs.

ACE inhibitors and other antihypertensive medications can reduce blood glucose levels. If necessary, the metformin dose can be adjusted.

Concomitant use of Siofor® with sulfonylurea derivatives, insulin, acarbose, salicylates may increase the hypoglycemic effect.

How to take it, course of use and dosage

The drug should be taken orally during or after a meal. The dose and mode of taking the drug, as well as the duration of treatment, are set by the attending physician depending on the level of glucose in the blood.

Adults

Monotherapy

The recommended starting dose is 500 mg (1 tablet of Siofor® 500 or 1/2 tablet of Siofor® 1000) 1-2 times / day or 850 mg (1 tablet of Siofor® 850) 1 time/day.

After 10-15 days after the start of taking the drug, a further gradual increase in the dose is possible, depending on the blood glucose level, to the average daily dose: 3-4 tablets of Siofor ® 500,2-3 tablets of Siofor® 850 preparation, or 2 tablets of Siofor® 1000 preparation. Gradually increasing the dose reduces the number of undesirable effects from the gastrointestinal tract.

The maximum dose is 3000 mg / day in 3 divided doses (6 tablets of Siofor ® 500 or 3 tablets of Siofor® 1000).

For patients who are prescribed high doses (2000-3000 mg/day), it is possible to replace 2 tablets of Siofor® 500 with 1 tablet of Siofor® 1000.

If a patient is transferred to treatment with Siofor® from therapy with another antidiabetic drug, stop taking the latter and start taking Siofor® in the doses indicated above.

Combined use with insulin

Siofor® and insulin can be combined to improve glycemic control. The standard initial dose is 500 mg (1 tablet of Siofor® 500 or 1/2 tablet of Siofor® 1000) 1-2 times / day or 850 mg (1 tablet of Siofor® 850) 1 time/day, with a gradual increase in the dose at intervals of approximately one week to an average daily dose of 3-4 tablets of Siofor® 500,2 tablets of Siofor® 1000 or 2-3 tablets of Siofor® 850; the dose of insulin is determined based on the concentration of glucose in the blood.

The maximum dose is 3000 mg / day in 3 divided doses.

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

Children aged 10-18 years

Monotherapy and combined use with insulin

The standard initial dose is 500 mg (1 tablet of Siofor® 500 or 1/2 tablet of Siofor® 1000) 1 time/day or 850 mg (1 tablet of Siofor® 850) 1 time/day.

After 10-15 days after the start of taking the drug, a further gradual increase in the dose is possible, depending on the level of glucose in the blood. Gradually increasing the dose reduces the number of undesirable effects from the gastrointestinal tract.

The maximum dose for children is 2000 mg / day (4 tablets of Siofor ® 500 or 2 tablets of Siofor® 1000) in 2-3 doses.

The dose of insulin is determined based on the level of glucose in the blood.

Overdose

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

Symptoms: with a significant overdose, lactic acidosis may develop, the symptoms of which are severe weakness, respiratory disorders, drowsiness, nausea, vomiting, diarrhea, abdominal pain, hypothermia, decreased blood pressure, reflex bradyarrhythmia. There may be muscle pain, confusion, and loss of consciousness.

Treatment: immediate withdrawal of the drug and emergency hospitalization are recommended. The most effective method of removing lactate and metformin from the body is hemodialysis.

Special instructions

Lactic acidosis is a serious pathological condition that occurs extremely rarely, associated with the accumulation of lactic acid in the blood, which can be caused by the accumulation of metformin. The described cases of lactic acidosis in patients treated with metformin were observed mainly in patients with diabetes mellitus with severe renal insufficiency. Prevention of lactic acidosis involves identifying all associated risk factors, such as decompensated diabetes, ketosis, prolonged fasting, excessive alcohol consumption, liver failure, and any condition associated with hypoxia. If lactic acidosis is suspected, immediate discontinuation of the drug and emergency hospitalization are recommended.

Since metformin is excreted by the kidneys, the plasma creatinine concentration should be determined before starting treatment, and then regularly. Special 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 NSAIDs.

Treatment with Siofor® should be temporarily replaced with other hypoglycemic drugs (for example, insulin) 48 hours before and 48 hours after the X-ray examination with intravenous use of iodine-containing contrast agents.

The use of Siofor® should be discontinued 48 hours before elective surgery under general anesthesia, with spinal or epidural anesthesia. Therapy should be continued after the resumption of oral nutrition or not earlier than 48 hours after surgery, provided that normal renal function is confirmed.

Siofor® does not replace diet and daily exercise-these types of therapy should be combined in accordance with the doctor’s recommendations. During treatment with Siofor®, all patients should adhere to a dietary diet with a uniform intake of carbohydrates throughout the day. Overweight patients should follow a low-calorie diet.

Standard laboratory tests for patients with diabetes mellitus should be performed regularly.

Before using Siofor® in children aged 10-18 years, the diagnosis of type 2 diabetes should be confirmed.

During one-year controlled clinical trials, the effect of metformin on growth and development, as well as puberty in children, was not observed, and data on these indicators with longer use are not available. In this regard, careful monitoring of the relevant parameters is recommended in children receiving metformin, especially in the prepubescent period (10-12 years).

Monotherapy with Siofor® does not lead to hypoglycemia, but caution is recommended when using the drug simultaneously with insulin or sulfonylureas.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

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

When Siofor® is co-administered with other hypoglycemic drugs (sulfonylureas, insulin, repaglinide), hypoglycemic conditions may develop, so caution should be exercised when driving vehicles and other potentially dangerous activities that require concentration of attention and speed of psychomotor reactions.

Form of production

Tablets

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Metformin

Conditions of release from pharmacies

By prescription

Dosage form

Tablets