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

Excipients: methyl methacrylate and ethyl acrylate copolymer [1: 2] in terms of dry matter - 72.00 mg, silicon colloidal dioxide - 29.70 mg, hypromellose - 319.00 mg, microcrystalline cellulose - 22.00 mg, magnesium stearate - 7.30 mg.

Shell composition: hypromellose-2910 - 39.60 mg, macrogol-6000 - 7.20 mg, glycerol-3.60 mg, talc-4.80 mg, titanium dioxide-4.68 mg, iron-oxide oxide yellow-0.12 mg.

Description:Oval biconvex tablets covered with a film membrane from light yellow to yellow. On the fracture, the core of the tablet is white or white with a yellowish hue 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 (1214 ng / ml) in blood plasma (TC_max) is 5 hours (in the interval of 4-10 hours) after a single dose of metformin in the dosage form of a tablet of prolonged action of 1000 mg.

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration (C_max) and the area under the "concentration-time" curve (AUC) increase in proportion to the dose received. After a single oral administration of metformin in the form of prolonged-release tablets at a dose of 2000 mg, AUC is similar to that observed after taking metformin in the form of tablets with a usual release at a dose of 1000 mg twice daily. The intra-individual variability of C_max and AUC after taking metformin in the form of prolonged-release tablets 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 meals, the AUC increases by 77% (C_max increases by 26% and TC_max slightly increases by about 1 hour).

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. C_max in the blood below C_maxin 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 60 ml / min);

- acute conditions occurring at a 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 cardiac or respiratory failure, acute myocardial infarction);

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

- liver failure, a violation of liver function;

- chronic alcoholism, acute alcohol poisoning;

- Pregnancy;

- lactic acidosis (including in the anamnesis);

- use for less than 48 hours before and within 48 hours after radioisotope or radiographic examination with the introduction of an iodine-containing contrast medium (eg, intravenous urography, angiography).section "Interaction with other drugs");

- compliance with the 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, performing heavy physical work, which is associated with an increased risk of developing lactic acidosis;

- during 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 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:

The preparation Gliiformin Prolong® is taken orally. Tablets are swallowed whole, without chewing, squeezed with enough liquid, once a day during or after 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

Transition from Metformin to Normal Release

The preparation Gliiformin Prolong® is prescribed as a supporting therapy for patients receiving metformin in the form of tablets with the usual release at a dose of 1000 mg or 2000 mg. When switching to Gliiformin ProLong®, the daily dose should be equivalent to the daily dose of metformin with normal release. Patients receiving metformin in the form of tablets with a normal release at a dose exceeding 2000 mg, the transition to Gliiformin ProLong® preparation is not recommended. 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 500 mg or 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 in the blood plasma with the possible subsequent transition to the preparation Gliiformin Prolong® 1000 mg. Slow increase in dose helps reduce side effects from the gastrointestinal tract.

Transition from another hypoglycemic drug

In case of transition from another hypoglycemic agent, the dose selection is performed as described above, starting with the administration of metformin with prolonged action of 500 mg or 750 mg.

Combination with insulin

To achieve better glycemic control metformin and insulin can be used as a combination therapy. The usual initial dose of metformin prolonged action is one 500 mg tablet or 750 mg once a day during dinner, while the insulin dose is selected based on the results of measuring the glucose concentration in the blood.Further, a transition to Gliiformin Prolong® 1000 mg is possible.

Daily dose

The maximum recommended dose of Gliiformin ProLong® is 2 tablets per day (2000 mg). If adequate glycemic control is not achieved with the maximum recommended daily dose of Gliiformin Prolong®, a transition to metformin with a normal release with 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.

Elderly patients and patients with impaired renal function

In elderly patients and patients with impaired renal function, the dose is adjusted based on an assessment of renal function that should be performed regularly (see "Special instructions").

Side effects:

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

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.

Impaired 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 or after a meal. Slow increase in dose may improve gastrointestinal tolerance.

Disorders 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 (redness 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 case of signs of lactic acidosis treatment with the drug should be stopped immediately, the patient urgently 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 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 Gliiformin Prolong® should be canceled depending on the function of the kidneys 48 hours before the X-ray 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.

Not recommended combinations

Alcohol: with acute alcohol intoxication, the risk of developing lactic acidosis increases, especially in the case of:

- 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 (eg, glucocorticosteroids (GCS) and tetracosactide (systemic and local action), beta2-adrenomimetics, azole is given, chlorpromazine when taken in high doses (100 mg per day) and diuretics: more frequent monitoring of blood glucose concentration, especially at the beginning of treatment, may be required. 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 because of the possible functional renal failure.Do not prescribe Glyformin Prolong® if creatinine clearance is less than 60 mL / min. Aigihyperteizivnye drugs class of angiotensin-converting enzyme (ACE) inhibitors can reduce the concentration of glucose in the blood. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of the drug Gliiformin Prolong® with derivatives of sulfonylurea, insulin, acarbose, salicylates may develop hypoglycemia.

Nifedipine increases absorption and C_maxmetformin.

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_max.

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 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, such as muscle cramps, 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 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 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.

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, therefore it does not affect the ability to drive vehicles and mechanisms.

Nevertheless, it is possible to develop 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 prolonged release, film-coated, 1000 mg.

Packaging:

For 30 or 60 tablets in a can of polymer or a bottle of plastic.

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

Storage conditions:

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-002674

Date of registration:23.10.2014 / 03.04.2017

Expiration Date:23.10.2019

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

Manufacturer: & nbsp

AKRIKHIN HFK, JSC Russia

Information update date: & nbsp30.04.2017

Illustrated instructions

Instructions

Glyformin Prolong® (Gliformin Prolong)