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

Active substance:
Metformin hydrochloride in terms of 100% substance	- 850 mg	- 1000 mg
Auxiliary substances of the core:
povidone (K 30)	- 120 mg	- 140 mg
hypromellose	- 160.8 mg	- 187.6 mg
calcium stearate	- 12 mg	- 14 mg
lactose monohydrate (milk sugar)	- 57.2 mg	- 58.4 mg
Shell accessories:
opadray® II blue,	- 35 mg	- 40 mg
including:
lactose monohydrate	- 40 %
hypromellose (hydroxypropyl methylcellulose 2910)	- 28 %
titanium dioxide	- 22,78 %
triacetin	- 8 %
dye diamond blue FCF, E 133, aluminum lacquer	-0,98 %
dye iron oxide black, E 172	- 0,22 %
colorant iron oxide yellow, E 172	-0,02 %

Description:The film-coated tablets are pale blue (850 mg dosage) and blue (1000 mg dose), oblong, biconvex, with risk on one side.Two layers are visible on the cross-section: the outer layer is light-blue (for a dosage of 850 mg) and blue (for a dosage of 1000 mg), the inner one is 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 lipid metabolism: it reduces the content of total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

The average time to reach the maximum concentration of metformin in the blood plasma after meals is 2.5 hours after a single oral intake of 1 tablet 850 mg and 5 hours after a single oral intake of 1 tablet at a dosage of 1000 mg (in the interval of 4-10 hours).

In an equilibrium state identical to the equilibrium state of metformin with normal release, the maximum concentration and area under the concentration-time curve increase in proportion to the dose taken. After a single oral administration of metformin in the form of prolonged-release tablets at a dose of 2000 mg, the area under the "concentration-time" curve is similar to that observed after ingestion of metformin in the form of tablets with the usual release at a dose of 1000 mg twice a day. The intra-individual variability of the maximum concentration and area under the concentration-time curve 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 area under the concentration-time "increases by 77% (the maximum concentration increases by 26% and the average time to reach the maximum concentration of metformin in the blood plasma increases by approximately 1 hour.) Metformin absorption from tablets of prolonged action 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 at a dose of 2000 mg.

Distribution

The connection with plasma proteins is negligible. The maximum concentration in the blood is below the maximum concentration in the plasma and is reached about the same time. The average volume of distribution ranges from 63 to 276 liters.

Metabolism

Metabolites in humans are not found.

Excretion

Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is more than 400 ml / min. which indicates 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 insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure (creatinine clearance less than 45 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 surgical procedures and trauma, when insulinoteropia is indicated (see section "Special instructions");

- liver failure, a violation of liver function;

- chronic alcoholism, acute alcohol poisoning;

- Pregnancy;

- Lactoacidosis (including in the anamnesis);

- use 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 the hypocaloric diet (less than 1000 kcal / day);

- lactose intolerance, lactase deficiency, glucose-galactose malabsorption;

- Children under 18 years of age due to the lack of clinical data on the 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;

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

- 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, as well as in case of pregnancy on the background of taking metformin, the drug should be canceled and insulin therapy 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:

Inside. Tablets are swallowed whole, without chewing, squeezed with enough liquid, once a day during or after dinner.

The dose of the drug is set 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

Recommended dose:

- For tablets with a dosage of 1000 mg - 1 tablet (1000 mg) 1 time per day during or after dinner.

For tablets with a dosage of 850 mg - 2 tablets (1700 mg) 1 time per day.

If the recommended dose does not manage to achieve adequate glycemic control, it is possible to increase the dose to the maximum.

Maximum recommended dose:

- for tablets with a dosage of 850 mg - 3 tablets once a day (2550 mg);

- for tablets with a dosage of 1000 mg - 2 tablets once a day (2000 mg).

If the maximum recommended dose once a day can not be adequately controlled glycemia, the maximum dose (for Metformin Long 1000 mg) can be divided into two methods: one tablet 1000 mg - at breakfast and one tablet 1000 mg - in dinner time. If adequate glycemic control is not achieved and in this case, a transition to metformin with a normal release with a maximum daily dose of 3000 mg.

For patients who do not take metformin, the recommended initial dose of metformin prolonged action is a dose of 500 mg (similar drugs are available at the indicated dosage) or 850 mg of Metformin Long once a day during supper.Every 10-15 days it is recommended to adjust the dose based on the results of measuring the concentration of glucose in the blood. Slow increase in dose contributes to better tolerability of the gastrointestinal tract.

In case of transition from another hypoglycemic agent, dose selection is performed as described above, starting with the appointment of metformin prolonged action at a dose of 500 mg (similar preparations are available at this dosage) or 850 mg of the drug Metformin Long with a possible subsequent transition to the drug Metformin Long with a dosage of 1000 mg .

Mezformin Long is prescribed as a maintenance therapy for patients taking metformin in the form of tablets with the usual release at a dose of 1000 mg or 2000 mg. To switch to a drug with prolonged action, the daily dose should be equivalent to the 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 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 prolonged action is 500 mg (similar preparations are available at this dosage) or 850 mg of Metformin Long once daily during supper, while the insulin dose is selected based on the results of measuring the blood glucose concentration. Further, it is possible to switch to Metformin Long with a dosage of 1000 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 of metformin prolonged action is 500 mg (similar drugs are available at this dosage) or 850 mg of Metformin Long 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 are adjusted for the dose based on renal function assessment, which should be done regularly (see "Special instructions").

Duration of treatment

Metformin 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 Metformin 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

From the side of 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, rash.

If any of the side effects indicated in the drug instructions are aggravated or other side effects not indicated in the instructions are noted, 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 signs of lactic acidosis, treatment with npena- rat must be stopped immediately, the patient must be hospitalized immediately and, after determining the lactate content, 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 radio-contrast media: 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 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 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 (eg, glucocorticosteroids and tetracosactide (systemic 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, especially at the beginning of treatment, may be required. If necessary, the dose of the drug Metformin Long 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 administer Metformin Long if the creatinine clearance is below 60 mL / min.

With the simultaneous use of the drug Metformin Long with derivatives of sulfonylurea, insulin, acarbose, salicylates may develop hypoglycemia. Nifedipii increases the absorption and maximum concentration of 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 maximum concentration.

With the simultaneous use of metformin prolonged action with kolesevelam, the level of metformin in the blood may increase, with a dose adjustment or a more stringent control of blood sugar levels for the safe administration of both drugs. You should see your doctor if your condition worsens or worse, such as nausea, vomiting, diarrhea, flatulence, dyspepsia. Immediately consult a doctor if weakness develops, muscle pain, chills, increased drowsiness, abdominal pain or discomfort, slow or irregular heartbeats, shortness of breath and other unusual symptoms, as these may be early signs of such a rare but serious side effect metformin, as lactic acidosis.

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.

It is necessary to take into account the risk of developing lactic acidosis with the appearance of non-specific signs, as well as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe asthenia.

Lakagoacidosis 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 surgery and can be continued no earlier than 48 hours after,that during the examination of 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 afterwards, at least once a year in patients with normal night function and 2 to 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 renal function in elderly patients, with simultaneous use of antihypertensive drugs, direc- tives 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 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, it is recommended to use caution 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 Metformin 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 the drug Metformin Long does not cause hypoglycemia, therefore 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 of prolonged action, film-coated, 850 mg and 1000 mg.

Packaging:

By 10, 30, 60 tablets in cans of polymer from polyethylene or polypropylene.

By 5, 10, 20 tablets in a contour mesh box made of polyvinyl chloride film and aluminum foil printed lacquered or paper with polyethylene coating. On 1 bank or 2, 6, 12. 20, 24 contour cell packs of 5 tablets, or 1, 3, 6, 10, 12 contour cell packs of 10 tablets, or 3, 5, 6 outline packs of 20 tablets together with instructions for use put in a pack of cargos.

Storage conditions:

In a dry, protected from light 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003855

Date of registration:22.09.2016 / 18.10.2017

Expiration Date:22.09.2021

The owner of the registration certificate:BIOSINTEZ, PAO BIOSINTEZ, PAO Russia

Manufacturer: & nbsp

BIOSINTEZ, PAO Russia

Information update date: & nbsp11.05.2018

Illustrated instructions

Instructions

Metformin Long (Metformin long)