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

Composition:In 1 tablet, coated with a film coating, contains: active substance metformin hydrochloride 500.0 mg, 850.0 mg and 1000.0 mg; Excipients: povidone K-30, povidone K-90, silicon dioxide colloid, magnesium stearate, sheath Opadrai white Y-1-7000H (hypromellose E464, titanium dioxide E171, macrogol-400).

Description:

Tablets 500 mg: white or almost white oval tablets covered with a film sheath, engraved "93" on one side and "48" on the other.

Tablets 850 mg: white or almost white oval tablets covered with a film sheath, engraved "93" on one side and "49" on the other.

Tablets 1000 mg: white or almost white oval tablets covered with a film sheath, with a risk on both sides,with the engraving "9" to the left of the risks and "3" to the right of the risks on one side and "72" to the left of the risks and "14" to the right of the risks to the other.

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

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin is an oral hypoglycemic agent from the group of bituamides. In patients with diabetes mellitus, it reduces the concentration of glucose in the blood by suppressing gluconeogenesis in the liver, reducing the absorption of glucose from the gastrointestinal tract (GIT) and increasing its utilization in tissues by increasing their sensitivity to insulin (predominantly striated muscle, to a lesser extent - adipose tissue).

Does not stimulate the secretion of insulin, hypoglycemic reactions do not cause. Has an effect on lipid metabolism - reduces the concentration in the blood serum of triglycerides, cholesterol and low density lipoproteins. Stimulates intracellular glycogenesis, activating glycogen synthase. On the background of taking metformin, the patient's body weight either remains stable or moderately decreases.

Pharmacokinetics:

Suction. After taking the drug inside metformin sufficiently absorbed from the digestive tract. Absolute bioavailability is 50-60%. The maximum plasma concentration (Cmax) is approximately 2 μg / ml or 15 μmol / L and is reached after 2.5 hours. After 7 hours, the absorption from the gastrointestinal tract terminates and the concentration of metformin in the plasma gradually decreases. With simultaneous intake of food, absorption of metformin decreases and slows down.

Distribution. Metformin practically does not bind to plasma proteins and is quickly distributed into body tissues. Penetrates into red blood cells. It accumulates in the salivary glands, liver and kidneys. The apparent volume of distribution is 63-276 liters.

Metabolism and excretion. It is excreted by the kidneys unchanged. The clearance of metformin in healthy individuals is 400 ml / min, which indicates active glomerular filtration and tubular secretion. The half-life (T_1/2) is approximately 6.5 h. Pharmacokinetics in special clinical cases. In patients with renal failure, renal clearance of metformin decreases in proportion to a decrease in creatinine clearance, T_1/2increases, which leads to an increase in the concentration of metformin in the blood. Cumulation is possible.

Indications:Diabetes mellitus type 2 in adults (especially in obese patients) with ineffectiveness of diet and exercise as a monotherapy or in combination with other oral hypoglycemic agents or insulin.

Contraindications:

- Hypersensitivity to metformin or to any auxiliary substance of the drug;

- diabetic ketoacidosis, diabetic precoma, coma;

- renal failure or renal dysfunction (creatinine clearance (CC) less than 60 ml / min);

- acute conditions that occur with a risk of developing renal dysfunction:

- Dehydration (with diarrhea, vomiting), fever, severe infectious diseases;

- the state of hypoxia (shock, sepsis, kidney infections, bronchopulmonary diseases);

- clinically pronounced manifestations of acute and 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;

- lactic acidosis (including in the anamnesis);

- use less than 48 hours before and within 48 hours after radioisotope or X-ray studies with the introduction of an iodine-containing contrast medium (see section "Interaction with other drugs");

- a period of less than 48 h before and within 48 h after surgery under general anesthesia, spinal or epidural anesthesia;

- compliance with a low-calorie diet (less than 1000 kcal / day);

- children's age till 10 years;

- Pregnancy.

Carefully:In people over 60 years of age, performing heavy physical work (increased risk of lactic acidosis), the period of breastfeeding.

Pregnancy and lactation:

The drug is contraindicated for use in pregnancy and during breastfeeding.

When planning or onset of pregnancy, Metformin-Teva should be discontinued and insulin therapy should be prescribed. The patient should be warned about the need to inform the doctor in case of pregnancy. Mother and child should be monitored.

It is not known whether metformin with breast milk. If it is necessary to use the drug during lactation, breastfeeding should be stopped.

Dosing and Administration:

Inside, during or immediately after a meal.

Monotherapy and combination therapy with other oral hypoglycemic agents

Initial dose: 500-1000 mg once a day in the evening. After 7-15 days in the absence of adverse effects from the gastrointestinal tract appoint 500-1000 mg 2 times a day in the morning and in the evening. A further gradual increase in the dose is possible depending on the concentration of glucose in the blood.

Supportive dose: 1500-2000 mg / day. To reduce side effects from the GIT, the dose should be divided into 2-3 doses. Maximum dose: 3000 mg / day in 3 divided doses. A slow increase in the dose may help improve the gastrointestinal tolerance of the drug.

Patients receiving metformin in doses of 2000-3000 mg / day, can be transferred to the dose of 1000 mg. The maximum recommended dose: 3000 mg / day in 3 divided doses.

When switching to therapy with another hypoglycemic agent, stop taking another medication and start taking Metformin-Teva in the dose indicated above.Combinations with insulin

Metformin-Teva and insulin can be used as a combination therapy to achieve better glycemic control.

Metformin-Teva is prescribed in a usual initial dose of 500 mg or 850 mg 2-3 times a day. The dose of insulin is selected based on the results of measuring blood glucose. After 10-15 days, the dose is adjusted depending on the concentration of glucose in the blood. The maximum dose of metformin in combination treatment: 2 g / day in 2-3 divided doses.

In elderly patients, the daily dose should not exceed 1000 mg / day.

Side effects:

Side effects are classified according to the following frequency: very often - no less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

From the central nervous system: often - a taste disorder (metallic taste in the mouth).

From the digestive system: very often - nausea, vomiting, abdominal pain, lack of appetite, arising during the initial period of treatment and in most cases spontaneously passing; single cases - a violation of liver function indicators or hepatitis, completely disappearing after drug withdrawal.

Allergic reactions: very rarely - erythema, itchy skin, rash.

From the side of metabolism: very often - lactic acidosis (requires withdrawal of the drug).

Other: very rarely - with prolonged use develops hypovitaminosis B12.

Overdose:

Symptoms

With the use of metformin in a dose of 85 g there was no hypoglycemia, but there was a development of lactic acidosis. The early symptoms of lactic acidosis are nausea, vomiting, diarrhea, lower body temperature, abdominal pain, muscle pain, there may be more rapid breathing, dizziness, impaired consciousness and coma development.

Treatment

If signs of lactic acidosis drug treatment must be stopped immediately, the patient hospitalized immediately and determine 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: Radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis in patients with diabetes mellitus against the background of functional renal failure.The use of metformin should be discontinued 48 hours before the X-ray examination in patients with creatinine clearance less than 45 ml / min with intravenous iodine-containing radiopaque agents or in patients with creatinine clearance less than 60 ml / min using intra-arterial iodine-containing radiopaque agents. The use of metformin can be resumed no earlier than 48 hours after the radiographic examination, provided that during the examination the renal function was found to be normal.

Unrecommended combinations

Alcohol and medicines containing ethanol: with the simultaneous use of metformin with alcohol, drugs containing ethanol, the risk of developing lactic acidosis during acute alcohol intoxication increases, especially when fasting or following a low-calorie diet, as well as with liver failure. When taking the drug, avoid drinking alcohol and taking medications containing ethanol.

Combinations that require caution

Diaazol: with the simultaneous use of metformin with danazol possible development of a hyperglycemic effect.If it is necessary to treat danazol and after stopping its intake, correction of metformin dose under the control of glycemia is required.

Chlorpromazine in high doses (100 mg / day) reduces the release of insulin and increases the concentration of glucose in the blood. With simultaneous use with neuroleptics and after discontinuation of their intake, correction of metformin dose under the control of glycemia is required.

Glucocorticosteroids (GCS) reduce glucose tolerance and increase the concentration of glucose in the blood, in some cases, causing ketosis. If it is necessary to use this combination, and after stopping the GCS, correction of the dose of metformin under the control of glycemia is required.

Diuretics: with the simultaneous use of "loop" diuretics and metformin, there is a risk of lactic acidosis because of the possible emergence of functional renal failure.

Prescribed as an injection of beta2-adrenomimetics: increase the concentration of glucose in the blood due to stimulation of beta-3-adrenergic receptors. In this case, it is necessary to monitor the concentration of glucose in the blood. If necessary, the appointment of insulin is recommended.

With the simultaneous use of the above medicines, more frequent monitoring of the glucose level in the blood may be required, especially at the beginning of the treatment. If necessary, the dose of metformin can be adjusted during treatment and after its termination.

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

With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose and salicia, an increase in hypoglycemic activity is possible. Nifedipine increases the absorption and C max of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, chiidine, 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 Cmax.

Special instructions:

Lactic acidosis is a rare but serious metabolic complication (high mortality in the absence of emergency treatment), which can arise from the cumulation of metformin.

There are reports of cases of lactic acidosis in the use of metformin, mainly in patients with diabetes mellitus and concomitant expressed renal failure. To reduce the incidence of lactic acidosis, other related factors, such as poorly controlled diabetes mellitus, ketosis, prolonged fasting, alcoholism, hepatic insufficiency, and any condition associated with hypoxia, must be considered.

The risk of developing lactic acidosis with such non-specific symptoms as muscular spasms, accompanied by dyspeptic disorders, abdominal pain, general weakness and severe disability should be considered. Lactic acidosis is characterized by the appearance of acidotic dyspnea, abdominal pain and hypothermia, followed by the development of coma. Laboratory indicators indicate a decrease in blood pH (less than 7.25), an increase in the concentration of lactate in the blood plasma above 5 mmol / l, an increase in the anion gap and a lactate / pyruvate ratio. If you suspect a lactic acidosis, stop taking the medication and consult a doctor immediately.

Because the metformin (by the Cockcroft-Gault formula with the use of the value of the concentration of creatinine in the blood plasma): 1 time per year in patients with normal renal function, 2-4 times a year in patients with QC at the lower border of the norm and in elderly patients.

Caution should be exercised when used in elderly patients. often a decrease in kidney function is asymptomatic in them. Care should also be taken in other situations where the kidney function may be impaired, for example, during the initial period of therapy with antihypertensive drugs, diuretics, non-steroidal anti-inflammatory drugs.

Metformin-Teva should be discontinued 48 hours before the X-ray examination with intravascular injection of iodine-containing radiopaque agents.

The drug therapy can be continued after 48 hours after the end of the study and only provided that after examination the kidney function was recognized as normal.

Metformin-Teva should be discontinued 48 hours before the scheduled surgical operation, under general anesthesia, spinal or epidural anesthesia.The drug therapy can be continued no earlier than 48 hours after the operation or resumption of food by the patient and only if it is confirmed that the kidney function in the patient is normal. Before using Metformin-Teva in children, it is necessary to obtain confirmation of the diagnosis of type 2 diabetes. Results of clinical trials of metformin in children who continued for 1 year showed no effect of metformin on growth and puberty in children, and also showed that the effectiveness and safety of metformin in children is the same as in adults. However, with the use of Metformin-Teva in children it is recommended to continue monitoring the parameters of their growth and puberty. The most careful control is needed in children aged 10-12 years.

All patients with diabetes, including those with excessive body weight, should strictly adhere to the doctor's recommendations for diet and exercise regimen.

During the treatment, standard laboratory tests should be performed regularly to monitor diabetes mellitus.

Hypovitaminosis B12 when taking Metformin-Teva is caused by a violation of absorption of vitamin B12 and has a reversible character. With the withdrawal of Metformin-Teva, the signs of hypovitaminosis B12 disappear quickly.

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

Monotherapy with Metformin-Teva does not cause hypoglycemia and therefore does not affect the ability to drive vehicles and other mechanisms.

Caution should be exercised when using Metformin-Teva with other hypoglycemic agents (sulfonylurea derivatives, insulin, etc.) in connection with the possibility of developing hypoglycemic conditions in which the ability to drive vehicles and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Tablets, film-coated, 500 mg, 850 mg and 1000 mg.

Packaging:

For 10 tablets in a blister of PVC / PVDC / aluminum foil.

For 3 or 6 blisters together with instructions for use in a cardboard bundle.

When packing on the territory of the Russian Federation:

For 10 tablets in a blister of PVC / PVDC film according to GOST 25250-88 or Eur.Ph current edition and aluminum foil according to GOST 745-2014 or TU 9570-001-63543701-11.

For 3 or 6 blisters together with instructions for use in a cardboard box in accordance with GOST 12303-80 from cardboard type chrome or chrome-ersatz according to GOST 7933-89 or other similar quality.

Packing in bulk:

For 5 kg, 10 kg, 15 kg, 20 kg or 30 kg of tablets are placed in a double plastic bag with a desiccant located between the packages. Packages are sealed tightly with a clamp and / or a plastic corking tape.

1 packet is placed in a cardboard or plastic drum. The drum is labeled.

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 the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-000028

Date of registration:09.11.2010 / 07.07.2016

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp12.05.2018

Illustrated instructions

Instructions

Metformin-Teva (Metformin-Teva)