Glucophage Long - instructions for use, dose, side effects, contraindications

Excipients: carmellose sodium - 50.0 mg, hypromellose 2910 - 10.0 mg, hypromellose 2208 - 358.0 mg, cellulose microcrystalline - 102.0 mg, magnesium stearate - 3.5 mg.

Description:

Shaped, biconvex tablets white or almost white, engraved "500" on one side.

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

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin - biguanide with hypoglycemic action, reducing both basal and postprandial concentrations glucose in the 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 lipid metabolism: it reduces the content of total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

After oral administration of the drug in the form of a sustained-release tablet, the absorption of metformin is slowed compared to the tablet with the usual release of metformin. The time to reach the maximum concentration (TC_m_Oh) is 7 hours. At the same time, the TS_m_Oh for a tablet with a conventional release is 2.5 hours.

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration (C_ma_x) 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 the usual release of two times a day.

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

The absorption of metformin from prolonged-action tablets does not change depending on the intake of food. There is no cumulation with multiple admission to 2000 mg of metformin in the form of long-acting tablets.

Distribution

The connection with plasma proteins is negligible. FROM_m_Oh in the blood below C_m_Ohin plasma and is reached approximately in the same time. The average volume of distribution (V_ᵈ) varies 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 is about 6.5 hours. With impaired renal function, the clearance of metformin decreases in proportion to the creatinine clearance, the half-life increases, 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 taking place with the risk of developing renal dysfunction: dehydration (with chronic or severe diarrhea, repeated 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 (including acute heart failure, chronic heart failure with unstable hemodynamics, respiratory failure, acute myocardial infarction);

- extensive surgery and trauma, when insulin therapy is indicated (see section "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 section "Interaction with other drugs");

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

- Children under 18 years of age due to lack of application data.

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

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

- in the period of breastfeeding.

Pregnancy and lactation:

When planning pregnancy, as well as in case of pregnancy on the background of Glucophage® Long drug, the drug should be canceled, and insulin therapy is prescribed. The patient should inform the doctor about the onset of pregnancy against the background of Glucophage® Long.

Since there is no data on the penetration of metformin into breast milk, this drug is contraindicated in breastfeeding. If you need to use the drug Glucophage Long prolonged action during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Glucophage® Long in the form of long-acting tablets 500 mg is taken orally. Tablets are swallowed whole, without chewing, squeezed with a small amount of liquid, once a day during dinner.

The dose of Glucophage® Long in the form of long-acting tablets is selected by the doctor individually for each patient based on the results of measuring the concentration of glucose in the blood.

Monotherapy and combination therapy in combination with other hypoglycemic agents

- For patients not receiving metformin, the recommended initial dose of Glucophage® Long is 500 mg once a day during dinner.

- Depending on the concentration of glucose in the blood plasma, a slow increase in the dose (by 500 mg) is possible every 10-15 days, until the maximum daily dose (2000 mg) is reached. Slow increase in dose helps reduce side effects from the gastrointestinal tract.

- For patients already receiving metformin treatment, the initial dose of Glucophage® Long should be equivalent to the daily dose of tablets with normal release.

- Patients receiving metformin in the form of tablets with the usual release of the active ingredient at a dose exceeding 2000 mg, the transition to Glucophage® Long is not recommended.

- In case of planning a transition from another hypoglycemic agent, stop taking another medication and start taking Glucophage® Long 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 Glucophage® Long is one 500 mg tablet once a day during dinner,while a dose of insulin is selected based on the results of measuring the concentration of glucose in the blood.

Daily dose

The maximum recommended dose of Glucophage® Long is 4 tablets 500 mg per day (2000 mg). If the maximum recommended dose is not administered once a day during dinner, adequate glycemic control can not be achieved, then the maximum dose can be divided into two doses: 2 tablets 500 mg - at breakfast and 2 tablets 500 mg - during dinner.

If adequate glycemic control is not achieved with taking 2000 mg of Glucophage® Long, prolonged-release tablets, a switch to metformin with the usual release of the active ingredient (eg Glucophage®, film-coated tablets) with a maximum daily dose of 3000 mg.

Patients with renal insufficiency

Metformin 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 once a day. 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

Because of the possible decrease in renal function, the dose of metformin is corrected on the basis of an evaluation of renal function that must be performed regularly, at least 2 times per year.

The duration of the course of treatment Glucophage® Long should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.

Dose skip

In case of missed intake of the next dose, the patient should take the next dose at the usual time. Do not take a double dose of Glucophage® Long.

Side effects:

The frequency of side effects of the drug is assessed as follows:

Very frequent: ≥1 / 10

Frequent: ≥1 / 100, <1/10

Infrequent: ≥ 1/1000, <1/100

Rare: ≥ 1/10 000, <1/1000

Very rare: <1/10 000

Disorders from the metabolism and nutrition:

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

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, 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 during the meal. Slow increase in dose may improve gastrointestinal tolerance.

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.

Disturbances from the skin and subcutaneous tissues:

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

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

Overdose:

When metformin was used at a dose of 85 g (42.5 times the maximum daily dose), no development of hypoglycemia was observed. 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 the appearance of signs of lactic acidosis, the drug should be discontinued immediately, the patient should be hospitalized immediately and, after determining 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

Iodinated radiopaque means: 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 Glucophage Long should be discontinued 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 found to be normal.

Unrecommended combinations

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

- malnutrition, compliance with a 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), 6eta₂-adrenomimetics, danazol,chlorpromazine when taken in high doses (100 mg per day) anddiuretics): more frequent monitoring of blood glucose concentration may be required, especially at the beginning of treatment. If necessary, the dose of Glucophage® Long can be adjusted during and after treatment, 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 the simultaneous use of Glucophage® Long withderivatives 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 when used simultaneously with metformin in the form of long-acting tablets increases the concentration of metformin in the blood plasma (an increase in AUC without a significant increase in C_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, should be considered.

Lactoacidosis is characterized by severe malaise with general weakness, acidotic dyspnea, vomiting, abdominal pain, muscle cramps and hypothermia followed by coma.

Diagnostic laboratory 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 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 is excreted by the kidneys, before the beginning of treatment and regularly in the subsequent,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 limit of the norm.

Special caution should be exercised in cases of possible impairment of kidney function in elderly patients, while using antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

Patients with cardiac insufficiency have a higher risk of developing hypoxia and kidney failure. Patients with chronic heart failure should regularly monitor cardiac function and kidney function during taking metformin. The use of metformin in acute heart failure and chronic heart failure 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 clinician about 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 when monotherapy does not cause hypoglycemia, but caution should be exercised when used in combination with insulin or other oral hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide, 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 the drug Glucophage® Long can be excreted 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 Glucophage® Long does not cause hypoglycemia, so it does not affect the ability to drive vehicles and mechanisms.

Nevertheless, the development of hypoglycemia in the use of metformin in combination with other hypoglycemic drugs (derivatives of sulfonylureas, insulin, repaglinide and etc.). When symptoms of hypoglycemia occur, do not drive vehicles and mechanisms.

Form release / dosage:Long-acting tablets, 500 mg.

Packaging:

For 15 tablets in a blister of PVC and aluminum foil, 2 or 4 blisters together with instructions for use are placed in a cardboard box.

The blister and cardboard tutu bear the symbol "M" to protect against tampering.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-002098/10

Date of registration:16.03.2010 / 30.06.2015

Expiration Date:Unlimited

The owner of the registration certificate:Merck Sante ca.c.Merck Sante ca.c. France

Manufacturer: & nbsp

MERCK SANTE, s.a.s. France

Representation: & nbspMERK, LLCMERK, LLCRussia

Information update date: & nbsp22.04.2017

Illustrated instructions

Instructions

Glucophage® Long (GLUCOPHAGE® LONG)