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

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.

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. Time to reach the maximum concentration (TC_mOh) is 7 hours. At the same time, the TS_mOh for a tablet with a conventional release is 2.5 hours.

After a single oral intake of 2000 mg of metformin in the form of long-acting tablets, the concentration-time curve (AUC) is similar to that observed after taking 1000 mg of metformin in the form of tablets with the usual release twice a day.

When taking long-acting tablets on an empty stomach, AUC decreases by 30%, but the maximum concentration (C_mOh) and TS_mOh remain unchanged.

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

Distribution

The connection with plasma proteins is negligible. FROM_mOh in the blood below C_mOh in plasma, and is reached approximately in the same time. Average volume of distribution (Vd) varies in the range of 63-276 liters.

Metabolism

Metformin does not participate in the metabolism, and, since the connection with plasma proteins is negligible, it is metabolized in an unbound form. Metabolites in humans are not found. Metformin is excreted unchanged by the kidneys.

Excretion

The renal clearance of metformin is> 400 ml / min, indicating that metformin is excreted by 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 that 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 (seeSection "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 studies on the penetration of metformin in breast milk in humans have not been conducted, this drug is contraindicated in breastfeeding.

If you need to use Glucophage® Long during lactation, breastfeeding should be discontinued.

Dosing and Administration:

The drug Glucophage® Long in the form of long-acting tablets 750 mg is taken orally. The tablets are swallowed whole, without chewing, squeezed with enough 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 who do not take metformin, the recommended initial dose of Glucophage® Long is 750 mg once a day during dinner.

- Every 10-15 days it is recommended to adjust the dose based on the results of measuring the concentration glucose in the blood plasma. Slow increase in dose helps to reduce side effects from the gastrointestinal tract.

- The recommended dose of the drug Glucophage® Long is 2 750 mg tablets once a day. If, when taking the recommended dose, you can not achieve adequate control of glycemia, it is possible to increase the dose to maximum - 3 tablets 750 mg Glucophage® Long once a day.

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

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

- In the case of planning a transition from another hypoglycemic means, it is necessary to stop taking another remedy and start taking Glucophage® Long in the dose specified above.

Combination with insulin

To achieve better control of blood glucose metformin and insulin can be apply as a combined therapy. The usual initial dose of Glucophage® Long is one 750 mg tablet once a day during dinner, while the insulin dose is selected based on the results of measuring blood glucose.

Daily dose

The maximum recommended dose of Glucophage® Long-3 tablets 750 mg per day (2250 mg).

If adequate glycemic control is not achieved by taking the maximum recommended dose of Glucophage® Long, tablets prolonged action, transition 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 disease insufficiency

Metformin can be used in patients with renal insufficiency of moderate severity (creatinine clearance 45-59 ml / min) only in the absence of conditions that may increase the risk of lactic acidosis. The initial dose is 750 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 based on an assessment of renal function that should be performed regularly (See "Specific guidance").

Duration 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; Single: can not be evaluated with the available data.

Side-effect is presented in order of decreasing importance:

Nervous system:

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

Gastrointestinal disorders:

Very often: nausea, vomiting, diarrhea, abdominal pain and lack of appetite.

The occurrence of these side effects is most likely in the initial treatment period and in most cases they spontaneously pass. To prevent symptoms, it is recommended to take metformin during or after a meal. Slow increase in dose may improve gastrointestinal tolerance.

Skin and subcutaneous tissue:

Very rarely: skin reactions, such as erythema, pruritus, urticaria.

Metabolic disorders:

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

With prolonged intake of metformin, a reduction in vitamin absorption may occur AT₁₂. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

Hepatobiliary disorders:

There are isolated reports of violations of liver function or hepatitis; After the withdrawal of metformin, undesirable phenomena completely disappear.

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, 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 (eg, glucocorticosteroids (GCS) and tetracosactide (system and local action), 6eta₂-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 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 with derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine enhances the absorption and FROM_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 metformin in 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 it is necessary to determine the clearance of creatinine before the beginning of treatment and regularly in the future, 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.

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.

Heart failure

Patients with cardiac insufficiency have a higher risk of developing hypoxia and kidney failure. Patients with chronic cardiac Insufficiency 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 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 the drug Glucophage® Long may 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 work with mechanisms. Nevertheless, patients should be cautioned about the risk of hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylureas, insulin, repaglinide).

Form release / dosage:Long-acting tablets, 750 mg.

Packaging:

For 15 tablets in a blister of PVC / aluminum foil or PVC / PVDH / 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:PL-000509

Date of registration:01.03.2011 / 28.03.2016

Expiration Date:Unlimited

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

Manufacturer: & nbsp

MERCK, KGaA Germany

MERCK SANTE, s.a.s. France

Representation: & nbspNycomed Distribution Ltd.Nycomed Distribution Ltd.

Information update date: & nbsp22.04.2017

Illustrated instructions

Instructions

Glucophage® Long (GLUCOPHAGE® LONG)