Metformin Long Canon - instructions for use, dose, side effects, contraindications

Excipients: hypromellose 2208 (hydroxypropyl methylcellulose 2208) 155 mg; hypromellose 2910 (hydroxypropylmethylcellulose 2910) 4.3 mg; silicon colloid dioxide 7.6 mg; magnesium stearate 7 mg; cellulose microcrystalline 26.1 mg.

1 tablet with a sustained release of 750 mg contains:

active substance: metformin hydrochloride 750 mg;

Excipients: hypromellose 2208 (hydroxypropylmethylcellulose 2208) 232.5 mg; hypromellose 2910 (hydroxypropylmethylcellulose 2910) 6.45 mg; silicon colloidal dioxide 11.4 mg; magnesium stearate 10.5 mg; microcrystalline cellulose 39.15 mg.

1 tablet with prolonged release of 1000 mg contains:

active substance: metformin hydrochloride 1000 mg;

Excipients: hypromellose 2208 (hydroxypropyl methylcellulose 2208) 310 mg; hypromellose 2910 (hydroxypropylmethylcellulose 2910) 8.6 mg; silicon dioxide colloidal 15.2 mg; magnesium stearate 14 mg; cellulose microcrystalline 52.2 mg.

Description:

Round biconvex tablets (dosage 500 mg); tablets oval biconvex (dosage 750 mg and 1000 mg), white or almost white.

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

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin is a biguanide with a hypoglycemic effect, which reduces both basal and postprandial glucose levels in blood plasma. Does not stimulate the secretion of insulin and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral receptors to insulin and the utilization of glucose by cells. Reduces the production of glucose by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays the absorption of glucose in the intestine.

Metformin stimulates the synthesis of glycogen, affecting glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters.

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

Metformin has a beneficial effect on the metabolism of lipids: reduces the content of total cholesterol, low density lipoprotein (LDL) and triglycerides.

Pharmacokinetics:

Absorption

With a single administration of the drug Metformin Long Canon 500 mg and 750 mg at a dosage of 1500 mg the mean time to reach the maximum concentration of metformin in the blood plasma (TC_m_Oh) is 5 hours (in the range of 4-12 hours). The average time to reach the maximum concentration of metformin (1214 ng / ml) in blood plasma (TS_m_Oh) after meals is 5 hours (in the range of 4-10 hours) after a single dose of 1 tablet of the drug Metformin Long Canon in the dosage form of the tablet with prolonged release of 1000 mg.

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration (C_m_Oh) and the area under the curve "concentration-time" (AUC) increase in proportion to the dose taken. After a single oral intake of 2000 mg of metformin in the form of long-acting tablets AUC is similar to that observed after taking 1000 mg of metformin in the form of tablets with a normal release 2 times a day.

The intra-individual variability of C_m_Oh and AUC after taking metformin in the form of tablets with prolonged release is similar to that observed after taking metformin in the form of tablets with normal release.

When taking metformin in the form of long-acting tablets at a dose of 1000 mg after a meal AUC increases by 77% (C_m_Ohincreases by 26% and TS_m_Oh increases by about 1 hour).

The absorption of metformin from the sustained-release tablets does not change with the composition of the food taken.

No cumulation is observed with repeated administration to 2000 mg of metformin in the form of sustained-release tablets.

Distribution

The connection with plasma proteins is negligible. FROM_m_Oh in the blood below C_max in plasma, and is reached approximately in the same time. Average volume of distribution (V_d) fluctuates in the range of 63-276 liters.

Metabolism

Metabolites in humans are not found.

Excretion

Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is> 400 ml / min, indicating that metformin is excreted due to glomerular filtration and tubular secretion.After oral administration, the elimination half-life (T_1/2) - about 6.5 hours.

With impaired renal function, the clearance of metformin decreases in proportion to the creatinine clearance, increases T_1/2, which can lead to an increase in the concentration of metformin in the plasma.

Indications:

Diabetes mellitus type 2 in adults (especially in patients with obesity) with ineffective diet and exercise:

- as a monotherapy;

- in combination with other oral hypoglycemic agents or with insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or impaired renal function (creatinine clearance less than 45 mL / min);

- acute conditions that occur with the risk of developing kidney dysfunction: dehydration (with chronic or severe diarrhea, multiple attacks of vomiting), severe infectious diseases (eg, respiratory infections, urinary tract infections), shock;

- clinically pronounced manifestations of acute or chronic diseases, which can lead to the development of tissue hypoxia (incl.acute heart failure or chronic heart failure with unstable hemodynamics, respiratory failure, acute myocardial infarction);

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

- hepatic failure, impaired liver function;

- chronic alcoholism, acute alcohol poisoning;

- pregnancy;

- lactic acidosis (including and 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 medium (eg, intravenous urography, angiography) (see "Interaction");

- compliance with hypocaloric diet (less than 1000 kcal / day);

- children under 18 years of age due to the lack of clinical data on use.

Carefully:

Apply Metformin Long Canon:

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

- in the period of breastfeeding;

- in patients with renal insufficiency (creatinine clearance 45-59 ml / min).

Pregnancy and lactation:

Decompensated diabetes mellitus during pregnancy is associated with an increased risk of congenital malformations and perinatal mortality.

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, 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 glucose level 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 in newborns with breastfeeding against metformin were not observed. However, due to the limited amount of data, the use of the drug in the period of 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:

Inside. Tablets are swallowed whole, without chewing, squeezed with enough liquid,1 time per day during or after dinner. The dose of the drug Metformin Long Canon is selected by the doctor individually for each patient, based on the results of measuring blood glucose concentrations.

Monotherapy and combination therapy in combination with other hypoglycemic agents

- For patients who do not take metformin, the recommended initial dose of the drug Metformin Long Canon is 500 mg or 750 mg 1 time per day, during or after dinner. 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. Slow increase in dose contributes to better tolerability of the gastrointestinal tract.

- In case of transition from another hypoglycemic agent, the metformin dose of Metformin Long canon is produced as described above, beginning with the appointment of the drug Metformin Long Canon 500 mg or 750 mg, with the possible subsequent transition to the drug Metformin Long Canon 1000 mg.

- Preparation Metformin Long canon 1000 mg should be taken 1 time per day during or after dinner.

- Metformin Long canon is prescribed as maintenance therapy for patients taking metformin in the form of tablets with the usual release at a dose of 1000 mg and 2000 mg. For the transition to the drug Metformin Long Canon 1000 mg daily dose should be equivalent to a daily dose of metformin with normal release.

- Patients receiving metformin in the form of tablets with the usual release in a dose exceeding 2000 mg, the transition to Metformin Long canon is not recommended.

Combination with insulin

To achieve better glycemic control metformin and insulin can be used as a combination therapy. The usual initial dose of Metformin Long canon is 1 tablet of 500 mg or 750 mg once a day during dinner, while the insulin dose is selected based on the results of measuring blood glucose. Further, it is possible to switch to Metformin Long Canon 1000 mg.

Daily dose

The maximum recommended dose of the drug is Metformin Long Canon 2000 mg. If the maximum recommended dose once a day can not be adequately controlled glycemia, the maximum dose can be divided into two methods: one tablet 1000 mg - at breakfast and one tablet 1000 mg - during dinner.If adequate control of hypoglycemia is not achieved, and in this case, it is possible to switch to metformin with normal release with a maximum daily dose of 3000 mg.

Patients with renal insufficiency

Metformin Long canon can be used in patients with moderate renal insufficiency (creatinine clearance 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis.

The initial dose is 500 mg or 750 mg once daily. The maximum dose is 1000 mg per day. Kidney function should be carefully monitored every 3-6 months. If the creatinine clearance is below 45 ml / min, the drug should be discontinued immediately.

Elderly patients

Elderly patients metformin dose is adjusted based on the evaluation of renal function, which must be done regularly (see "Special instructions").

Duration of treatment

Metformin Long canon should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.

Dose skip

If you miss the next dose, the next dose should be taken at the usual time.Do not take a double dose of Metformin Long Canon.

Side effects:

Classification of the incidence of side effects in accordance with the recommendations of the World Health Organization: very often (≥1/10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000) , very rarely (<1/10000), including individual messages; the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

Disorders from the metabolism and nutrition:

rarely: lactoacidosis (See "Special instructions").

With prolonged use of metformin, there may be a decrease in absorption of vitamin B)₂. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

Impaired nervous system:

often: a taste disorder (metallic taste in the mouth).

Violations from the side of the gastrointestinal tract:

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 Long Canon during or after meals.

Slow increase in dose may improve gastrointestinal tolerance.

Disorders from the liver and bile ducts:

rarely: violation of liver function and hepatitis; after the elimination of metformin, undesirable phenomena completely disappear.

Disturbances from the skin and subcutaneous tissues:

rarely: skin reactions such as erythema (redness of the skin), itching, hives.

If any of the side effects indicated in the manual are aggravated, or if there are other side effects not listed in the instructions, you should notify the doctor.

Overdose:

When metformin was used in a dose of up to 85 g (42.5 times the maximum daily dose), there was no development of hypoglycemia. However, lactoacidosis was observed in this case. Significant overdose or associated risk factors may lead to the development of lactic acidosis (see "Special instructions").

Treatment: in the case of signs of lactic acidosis, treatment with the drug must be stopped immediately, the patient immediately 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 Long canon should be canceled depending on the function of the kidneys 48 hours before or at the time of radiologic examination using iodine-containing radiopaque means and renewed no earlier than 48 hours after, provided that during the examination the renal function was recognized normal.

Not recommended combinations

Alcohol. In acute alcohol intoxication, the risk of lactic acidosis increases, especially in the following cases:

- malnutrition, low-calorie diet;

- hepatic insufficiency.

When taking the drug, avoid drinking alcohol and medications containing ethanol.

Combinations that require caution

Medicines with indirect hyperglycemic action (for example, glucocorticosteroids (GCS) and tetracosactide (system and local action), β2-adrenomimetics, danazol, chlorpromazine when taken in high doses (100 mg per day) and diuretics): more frequent monitoring of blood glucose concentration may be required, especially at the beginning of treatment. If necessary, the dose of Metformin Long canon can be adjusted during treatment and after its termination, based on the level of glycemia.

Diuretics: simultaneous administration of "loop" diuretics can lead to the development of lactic acidosis due to possible functional renal failure.

With simultaneous use of the drug Metformin Long Canon with derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine increases absorption and C_m_Oh 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_m_Oh.

Wheezevels with simultaneous use with metformin in the form of tablets with prolonged release increases the concentration of metformin in the blood plasma (increase AUC without a significant increase FROM_m_Oh).

Special instructions:

Lactic acidosis

Lactic acidosis is a rare but serious complication (high mortality in the absence of emergency treatment), which can arise from the cumulation of metformin. Cases of lactic acidosis with metformin were developed mainly 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 can help 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.

Lactoacidosis is characterized by severe malaise with general weakness, acidotic dyspnea, vomiting, abdominal pain, muscle cramps and hypothermia followed by coma. Diagnostic laboratory the indicators are a decrease in blood pH (less than 7.25), a plasma lactate concentration in excess of 5 mmol / l, an increased anion gap and a lactate / pyruvate ratio.If you suspect a metabolic acidosis, stop taking the medication and consult a doctor immediately.

Surgical operations

The use of metformin should be discontinued 48 hours before planned 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 the clearance of creatinine 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 creatinine clearance at the lower border norms.

Caution should be exercised when possible impairment of renal function in elderly patients, while using 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 should regularly monitor cardiac function and functionkidney during the intake of metformin. The use of metformin for acute insufficiency and chronic cardiac Insufficiency with unstable parameters of hemodynamics is contraindicated.

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 should continue to observe a hypocaloric diet (but not less than 1000 kcal / day). Patients should also exercise regularly.

Patients should inform the physician of any ongoing treatment and any infectious diseases such as a cold, an infection of the respiratory tract or a urinary tract infection.

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 oral hypoglycemic agents (eg, sulfonylureas or repaglinide derivatives, etc.). Symptoms of hypoglycemia are weakness, headache, dizziness, increased sweating, heart palpitations, impaired vision, or impaired concentration.

It is necessary to warn the patient that inactive components of Metformin Long canon can be released unchanged through the intestines, which does not affect the therapeutic activity of the drug.

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

Monotherapy with Metformin Long canon, sustained release tablets, does not cause hypoglycemia, so it does not affect the ability to drive vehicles and mechanisms.

Nevertheless, hypoglycemia may develop with metformin in combination with other hypoglycemic drugs (derivatives of sulfonylureas, insulin, repaglinide and etc.). When symptoms of hypoglycemia should not be managed means and mechanisms.

Form release / dosage:

Tablets with sustained release of 500 mg, 750 mg and 1000 mg.

Packaging:

For tablets with a dosage of 500 mg

For 10 or 15 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 60 tablets per can of polymer for medicines.

By 3, 6 contour cell packs of 10 tablets or 2,4 contour cellular packs of 15 tablets or 1 bank of polymer for medicines together with instructions for use in a pack of cardboard.

For tablets with a dosage of 750 mg and 1000 mg.

For 10 tablets in a planar cell packaging from a polyvinylchloride film and aluminum foil printed lacquered.

For 30, 60 tablets per can of polymer for medicines.

By 3, 6 contour squares or 1 bank polymer for medicines together with instructions for use in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C in the manufacturer's packaging.

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-004315

Date of registration:01.06.2017

Expiration Date:01.06.2022

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp22.06.2017

Illustrated instructions

Instructions

Metformin Long Canon (Metformin Long Canon)