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

Excipients: hypromellose (hydroxypropylmethylcellulose 200000 cps) - 248.00 mg, 330.00 mg, 374.00 mg, 294.00 mg; giprolose (hydroxypropyl cellulose) - 40,0 mg, 60.00 mg, 68.00 mg, 70.00 mg; magnesium stearate - 4.00 mg, 6.00 mg, 6.80 mg, 7.00 mg; silicon dioxide colloid (aerosil) - 4.00 mg, 6.00 mg, 6.80 mg, 7.00 mg; lactose monohydrate 4.00 mg, 48.00 mg, 54.40 mg, 22.00 mg.

Sheath: VIVACOAT® PA-1P-000 [hypromellose (hydroxypropyl methylcellulose 6 cps) - 9.36 mg, 14.04 mg, 15.99 mg, 16.38 mg; titanium dioxide 7.20 mg, 10.80 mg, 12.30 mg, 12.60 mg; polydextrose - 3.60 mg, 5.40 mg, 6.15 mg, 6.30 mg; talc - 2.40 mg, 3.60 mg, 4.10 mg, 4.20 mg; polyethylene glycol 3350 (macrogol 3350) 1.44 mg, 2.16 mg, 2.46 mg, 2.52 mg] 24.00 mg, 36.00 mg, 41.00 mg, 42.00 mg.

Description:Tabletki, covered with a film shell of white color, oval, biconvex. On the cut is white or almost white.

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 concentrations 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: reduces the content of total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

After oral administration of the drug in the form of long-acting tablets, the absorption of metformin is slowed compared to tablets with the usual release of metformin.

The time to reach the maximum concentration C_mOh with an average value of 5-7 hours (in the range of 4 to 12 hours). At the same time, the TS_mOh 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_mOh) 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 twice a day. The intra-individual variability of C_mOh 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_mOh in the blood below C_mOh 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 cardiac or 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 for 48 hours after radioisotope or X-ray studies with the introduction of an iodine-containing contrast medium (eg,internal urography, angiography) (see section "Interaction with other medicines");

- adherence to a hypocaloric diet (less than 1000 calories / day);

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

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

Carefully:

Apply the drug:

- 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 concentration 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:

Formethin® Long, sustained release tablets coated with a film coat, 500 mg, 750 mg, 850 mg, 1000 mg are taken orally. Tablets are swallowed whole, without chewing, squeezed with a small amount of liquid, once a day during dinner.

The dose of the drug 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 taking metformin, the recommended initial dose of Formethin® Long, sustained-release tablets coated with a film coat is 500 mg, 750 mg or 850 mg once a day during dinner.Every 10-15 days it is recommended to adjust the dose, depending on the concentration of glucose in the blood plasma. Slow increase in dose helps reduce side effects from the gastrointestinal tract;

- for patients already receiving metformin treatment, the initial dose of Formethin® Long should be equivalent to the daily dose of tablets with conventional release;

- patients receiving metformin in the form of tablets with the usual release of the active ingredient at a dose in excess of 2000 mg, it is not recommended to switch to Formethine® Long;

- in the case of scheduling a transition from another hypoglycemic agent, dose selection is performed as described above, starting with the appointment of Formethin® Long in a dose of 500 mg, 750 mg or 850 mg, with the possible subsequent conversion to Formethine® Long 1000 mg.

Combination with insulin

To achieve better control of blood glucose concentrations metformin and insulin can be used as a combination therapy. The usual initial dose of Formethin® Long is one 500 mg, 750 mg, or 850 mg tablet once a day during dinner, while the insulin dose is selected based on the results of measuring blood glucose. Further, it is possible to switch to Formethin® Long 1000 mg.

Daily dose

The maximum recommended dose of Formschg Long, sustained release tablets coated with a film coat, 500 mg and 1000 mg, respectively, is 4 tablets of 500 mg (2000 mg) or 2 tablets of 1000 mg (2000 mg) per day. If the maximum recommended dose of Formethin® Long 500 mg or 1000 mg once a day fails to achieve adequate glycemic control, the maximum dose can be divided into two doses: 2 tablets 500 mg - at breakfast and 2 tablets 500 mg - in dinner time, or one tablet of 1000 mg - at breakfast time and one tablet of 1000 mg during dinner.

The recommended dose of Formethine^® Long, sustained-release tablets coated with a film coat, 750 mg and 850 mg are respectively 2 tablets of 750 mg (1500 mg) or 2 tablets of 850 mg (1700 mg) once a day. If taking the recommended dose of Formethin® Long 750 mg or 850 mg fails to achieve adequate glycemic control, it is possible to increase the dose to a maximum of 3 tablets but 750 mg (2250 mg) or 3 tablets 850 mg (2550 mg) of Formethine ® Long once a day. To reduce the side effects of the gastrointestinal tract, a daily dose of Formethin® Long 750 mg or 850 mg can be divided into 2 divided doses.

If adequate glycemic control is not achieved when taking the maximum recommended dose of Formethine^® Long, a transition to metformin with the usual release of the active ingredient (eg Formethine® tablets 0.5 g, 0.85 g, 1.0 g) with a maximum daily dose of 3000 mg.

The use of the drug in 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 or 750 mg once daily. 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.

Application of the drug in elderly patients

Elderly patients are metformin dose adjusted based on renal function assessment, which should be done regularly, but at least 2 times per year (See "Special instructions").

Duration of treatment

Formethine® 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 Formethin® 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 vitamin absorption AT₁₂. 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

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. Taking Formethin® Long should be canceled depending on the function of the kidneys 48 hours prior to 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, requiring caution

Medicines with indirect hyperglycemic action (for example, glucocorticosteroids (GCS) and tetracosactide (system and local action), bEeta₂-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 Formethine^® 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 due to possible functional renal failure. Do not prescribe FORMETIN® Long if creatinine clearance is less than 45 mL / min.

With the simultaneous use of Formethin^® Long from 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_mOh.

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 in C_mOh).

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 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.

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 heart failure 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:

- Ppatients 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 the common cold, respiratory infections or urinary tract infections;

- 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 Formethin® Long can be excreted unchanged through the intestines, which does not affect the therapeutic activity of the drug;

- each tablet contains 4.00 mg, 48.00 mg, 54.40 mg, 22.00 mg of lactose. The drug is contraindicated in patients with lactose intolerance, lactase deficiency, glucose-galactose malabsorption.

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

Monotherapy with Formethin® 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:

Tablets with sustained release, film-coated, 500 mg, 750 mg, 850 mg and 1000 mg.

Packaging:

For 15 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 30, 40, 50, 60 or 70 tablets in a can of polymer or a polymer can with control of the first opening.

On the bank stick a label of paper label or writing, or self-adhesive labels from paper label or writing.

2 or 4 contour packs of 15 tablets together with the instructions for use are placed in a pack of cardboard.

A polymer can or polymer can with the control of the first opening together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 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-004110

Date of registration:30.01.2017

Expiration Date:30.01.2022

The owner of the registration certificate:PHARMSTANDART-TOMSKHIMFARM, OJSC PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-TOMSKHIMFARM, OJSC Russia

Representation: & nbspPHARMSTANDART-TOMSKHIMFARM, OJSCPHARMSTANDART-TOMSKHIMFARM, OJSCRussia

Information update date: & nbsp24.02.2017

Illustrated instructions

Instructions

Formethine® Long (Formetine® Long)