Glyformin Prolong - instructions for use, dose, side effects, contraindications

Excipients: methyl methacrylate and ethyl acrylate copolymer [1: 2] in terms of dry matter - 54.00 mg, silicon dioxide colloid - 22.27 mg, hypromellose - 239.25 mg, microcrystalline cellulose - 16.50 mg, magnesium stearate - 5.48 mg.

Shell composition: hypromellose-2910 - 29.70 mg, macrogol-6000 - 5.40 mg, glycerol-2.70 mg, talc-3.60 mg, titanium dioxide-3.51 mg, iron-oxide oxide yellow-0.09 mg.

Description:

Oval, biconvex tablets, covered with a film coat from light yellow to yellow.On the break the tablets are white or white with a yellowish tint of color.

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

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 concentration of total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

The mean time to reach the maximum concentration of metformin (1193 ng / ml) in the blood plasma (TFROM_m_Oh) is 5 hours (in the interval 4-12 hours) after a single oral intake 1500 mg of metformin in a sustained-release tablet formulation 750 mg.

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration (FROM_m_Oh) and the area under the "concentration-time" curve (AUC) increase in proportion to the dose taken. After a single intake of metformin in the form of long-acting tablets in a dose 2000 mg AUC is similar to that observed after taking metformin in the form of tablets with the usual release at a dose of 1000 mg twice a day. The intra-individual variability FROM_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 composition of the food taken.

There is no cumulation with repeated administration of metformin in the form of long-acting tablets in a dose of up to 2000 mg.

Distribution

The connection with plasma proteins is negligible. FROM_max 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 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 or 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 the lack of clinical data on use.

Carefully:

Use with caution:

- in persons 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:

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 level of glucose in the blood plasma at the level closest to the norm in order to reduce the risk of fetal malformations.

Metformin penetrates into 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:

The preparation of Glyformin Prolong is taken internally. The tablets are swallowed whole, without chewing, squeezed with enough liquid, once a day during dinner.

The dose of Gliiformin Prolong 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

Initiation of therapy in patients who had not previously taken metformin

In patients not taking metformin, the recommended initial dose of metformin prolonged action 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 glucose concentration inblood plasma. Slow increase in dose helps reduce side effects from the gastrointestinal tract. The recommended dose of Gliiformin Prolong is 2 750 mg tablets once a day. If you can not achieve adequate glycemic control when taking the recommended dose, you may increase the dose to a maximum of 3 tablets of 750 mg of Gliiformin Prolong preparation once a day.

Transition from Metformin to Normal Release

In patients receiving metformin in the form of tablets with conventional release, the daily dose should be equivalent to the daily dose of metformin with normal release when switching to Gliiformin Prolong. Patients receiving metformin in the form of tablets with the usual release in a dose exceeding 2000 mg, the transition to Gliiformin Prolong preparation is not recommended.

Transition from another hypoglycemic drug

In case of transition from another hypoglycemic agent, it is necessary to stop taking another remedy and start taking Gliiformin Prolong in the dose indicated above.

Combination with insulin

To achieve better glycemic control metformin and insulin can be used as a combination therapy. The usual initial dose of Gliiformin Prolong is one 750 mg tablet once a day during dinner, while the insulin dose is selected based on the results of measuring the blood glucose concentration.

Daily dose

The maximum recommended dose of Gliiformin Prolong is 3 tablets per day (2250 mg). If adequate glycemic control is not achieved when taking the maximum recommended daily dose of Gliiformin Prolong, it is possible to switch to metformin with normal release at a maximum daily dose of 3000 mg.

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 Gliiformin Prolong. Duration of treatment

Preparation Gliiformin Prolong should be taken daily, without interruption. In the event of discontinuation of treatment, the patient should inform the physician about this.

Patients with renal insufficiency

The drug can be used in patients with moderate renal insufficiency (creatinine clearance 45-59 ml / min) only in the absence of conditions that 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

Elderly patients due to a possible decrease in renal function metformin dose is adjusted based on a regular assessment of kidney function (see "Special instructions").

Side effects:

The frequency of side effects is presented according to the following classification: very often (≥ 1/10), often (≥ 1/100, <1/10), infrequently (≥ 1/1000, <1/100), rarely (≥ 1 / 10 000, <1/1000), very rarely (<1/10 000), the frequency is unknown (it is not possible to estimate the incidence from the available data).

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 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 must be hospitalized immediately and, by 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

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 Gliiformin Prolong should be canceled depending on the function of the kidneys 48 hours before or at the time of radiologic examination using iodine-containing radiocontrast agents 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 (for example, glucocorticosteroids (GCS) and tetracosactide (system and local action), beta₂-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 Gliiformin Prolong 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.

Hypotensive drugs, except for angiotensin-converting enzyme inhibitors, can change the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With simultaneous application of the preparation Gliiformin Prolong with derivatives of sulfonylurea, insulin, acarbose, salicylates possibly the development of hypoglycemia.

Nifedipine increases absorption and C_mOh 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 (increase AUC without a significant increase FROM_m_Oh).

Special instructions:

Lactic acidosis

Lactic acidosis is a rare but serious (high mortality in the absence of emergency treatment) complication, which may occur due to the cumulation of metformin. Cases of lactic acidosis with metformin were developed mainly in patients with diabetes mellitus with severe renal insufficiency.

Other related risk factors, such as uncompensated 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.

Consider the risk of developing lactic acidosis when non-specific signs appear, such as muscle cramps accompanied by dyspepsia,pain in the abdomen 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 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 scheduled surgical operations and can be continued no earlier than 48 hours after, provided that during the examination the kidney 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.

Special care should be exercised in cases of possible impairment of renal function in elderly patients, with simultaneous use of 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. In patients with chronic heart failure, it is necessary to regularly monitor cardiac function and kidney function during taking metformin. In acute heart failure and chronic heart failure with unstable hemodynamics, metformin 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.

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

Monotherapy with Gliiformin Prolong 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:

Tablets with sustained release, film-coated, 750 mg.

Packaging:

For 30 or 60 tablets in a jar of polyethylene, capped with a cap screwed from polyethylene.

For 30 or 60 tablets per bottle of polyethylene, capped with a cap screwed from polypropylene with control of the first opening or with an integrated desiccant.

Each jar or bottle together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

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-003700

Date of registration:23.06.2016 / 22.03.2017

Expiration Date:23.06.2021

The owner of the registration certificate:AKRIKHIN HFK, JSC AKRIKHIN HFK, JSC Russia

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Representation: & nbspAKRIKHIN OJSC AKRIKHIN OJSC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glyformin Prolong (Gliformin Prolong)