Metadien - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline - 100,00 mg, magnesium stearate - 10,00 mg, carmellose sodium -110,00 mg, hypromellose (K-100 M) - 200,00 mg, gelatin - 40,00 mg, povidone medium molecular weight - 40,00 mg.

Description:Tablets from white to almost white, oval, biconvex.

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

ATX: & nbsp

A.10.B.A.02 Metformin

Pharmacodynamics:Metformin inhibits gluconeogenesis in the liver, reduces the absorption of glucose from the intestine, enhances peripheral utilization of glucose, and also increases the sensitivity of tissues to insulin.In this case, it has no effect on the secretion of insulin by beta cells of the pancreas, does not cause hypoglycemic reactions.

Pharmacokinetics:

Suction

After oral administration of sustained-release tablets, metformin absorption is slowed compared to a tablet with the usual release of metformin. The time to reach the maximum concentration (TCmax) is 7 hours. The fluctuations in the maximum concentration of metformin (Cmax) and the area under the concentration-time curve (AUC) in individual patients in the case of taking metformin in the form of prolonged-release tablets are comparable to those of tablets with a conventional release profile.

Distribution

The connection with plasma proteins is negligible. Metformin partially associated with erythrocytes. Cmax in the blood is lower than Cmax in the plasma, and is reached approximately after the same time. At usual therapeutic doses, metformin is not metered in plasma, except in cases of impaired renal function. The average volume of distribution varies in the range of 63-276 liters.

Metabolism

Metformin is metabolized in an unbound form. Metabolites were not found.

Excretion

Metformin is excreted unchanged by the kidneys. The renal clearance of metformin is> 400 ml / min, indicating that metformin is excreted by glomerular filtration and tubular secretion. After oral administration, the elimination half-life is approximately 6.5 hours from the blood plasma and about 17.5 hours from the blood red blood cells.

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:Treatment of type 2 diabetes in adults with ineffective diet (especially in obese patients) as a monotherapy, or in combination with other oral hypoglycemic agents, or with insulin.

Contraindications:

Hypersensitivity to metformin hydrochloride 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 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, broncho-pulmonary 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"); hepatic failure, impaired liver function; chronic alcoholism, acute alcohol poisoning; pregnancy, the period of breastfeeding; lactic acidosis (including and in the anamnesis);

use for at least 2 days before and within 2 days after carrying out radioisotope or radiographic studies with the introduction of iodine-containing contrast medium (see section "Interaction with other drugs");

compliance with hypocaloric diet (less than 1000 kcal / day);

children's age till 18 years.

Carefully:With caution apply the drug in people over 60 years of age, performing heavy physical work, which is associated with an increased risk of developing lactic acidosis.

Pregnancy and lactation:

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. The patient should inform the doctor about the onset of pregnancy while taking the drug metformin.

Since there is no data on the penetration of metformin into breast milk, this drug is contraindicated in breastfeeding.

If you need to use the drug during lactation, breastfeeding should be discontinued.

Dosing and Administration:

Metadiene is administered internally. Tablets are swallowed without chewing, during dinner (1 time per day) or during breakfast and dinner (2 times a day). Tablets should be taken only during meals.

The dose of the drug is determined based on the glucose content in the blood plasma.

Monotherapy and combination therapy in combination with other hypoglycemic agents

Usual initial dose: 1 tablet 1 time per day during dinner.

When switching from the drug metformin with the usual release of the active ingredient, the initial dose of the drug Metadien should be equal to the daily dose of metformin with the usual release of the active ingredient.

Titration of the dose. Depending on the level of glucose in the blood plasma, every 10-15 days, the dose is slowly increased by 500 mg to the maximum daily dose. The maximum daily dose: 4 tablets 1 time per day during dinner.

If glucose control is not achieved at the maximum daily dose taken once a day, then the possibility of dividing this dose into several doses per day is as follows: 2 tablets at breakfast time and 2 tablets at dinner time.

Combination with insulin

When using the drug Metadien together with insulin, the usual initial dose of the drug is 1 tablet once a day, and the insulin dose is selected based on the results of measuring the glucose in the blood plasma.

Duration of treatment

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

Dose skip

If the next dose is missed, the next dose should be taken at the usual time. You can not double the dose of the drug.

Elderly patients and patients with reduced renal function

Elderly patients and patients with reduced renal function dose adjusted based on the evaluation of renal function, which must be done regularly less than 2 times a year.

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

Single: can not be evaluated with the available data.

Side-effect is presented in order of decreasing importance:

Nervous system:

Often: a taste disorder (metallic taste in the mouth).

Gastrointestinal disorders:

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, dividing the daily dose into 2 divided doses per day. Slow increase in dose may improve gastrointestinal tolerance. If the symptoms persist for a long time, stop taking the medication and seek medical advice.

Skin and subcutaneous tissue:

Very rarely: skin reactions such as erythema, pruritus, urticaria.

Metabolic disorders:

Very rarely: lactic acidosis (See "Special instructions").

Hepatobiliary disorders:

There are singlereports of impaired liver function or hepatitis; After the withdrawal of metformin, undesirable phenomena completely disappear.

If dyspeptic symptoms do not disappear, metformin treatment should be discontinued. Other: In patients treated with metformin for long periods may experience a decrease in vitamin B12 absorption, accompanied by a decrease in blood serum concentration. When detecting megaloblastic anemia, it is necessary to consider the possibility of such etiology.

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. 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: on the background of functional renal insufficiency in patients with diabetes mellitus, a radiological study using iodine-containing radiocontrast agents can cause the development of lactic acidosis.

Unrecommended combinations

Alcohol intake increases the risk of lactic acidosis during acute alcohol intoxication, especially in the following cases:

malnutrition, low-calorie diet of liver failure.

When taking the drug, avoid drinking alcohol and medications containing ethanol.

Combinations requiring special care

Danazol: It is not recommended simultaneous reception of danazolum in order to avoid hyperglycemic action of the latter. If necessary, treatment with danazol and after stopping the latter requires a dose adjustment of metformin under the control of glucose.

Chlorpromazine: when taken in high doses (100 mg per day) increases glycemia, reducing the release of insulin. When treating with neuroleptics and after stopping the intake of the latter, correction of the dose of the drug under the control of the level of glycemia is required.

Glucocorticosteroids (GCS) systemic and local effects reduce glucose tolerance, increase glycemia, sometimes causing ketosis. In the treatment of GCS, and after discontinuation of the latter, a dose adjustment of metformin is required under the control of 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 assign metformin, if the creatinine clearance is less than 60 ml / min.

Prescribed as an injection of beta2adrenomimetiki \ increase glycemia due to stimulation of beta-2 receptors. In this case, it is necessary to control glycemia. 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 treatmentand after its termination.

Angiotensin converting enzyme inhibitors and other antihypertensive agents drugs can reduce blood glucose. If necessary, the dose of metformin should be adjusted.

With the simultaneous use of metformin with derivatives of sulfonylurea, insulin, acarbose, salicylates, hypoglycemic action may be increased. Loop diuretics and non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of decreased kidney function. In this case, care must be taken when applying metformin.

Special instructions:

Lactic acidosis is extremely 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 in patients who received metformin, arose mainly in patients with diabetes mellitus with severe renal failure. Other associated risk factors, such as poorly controlled diabetes, ketosis, prolonged fasting, excessive alcohol consumption, 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 pains, convulsions accompanied by dyspeptic disorders, abdominal pain, general weakness and severe malaise should be considered. In this case, the patient should stop taking the drug and immediately consult a doctor.

The use of metformin should be discontinued 48 hours before planned surgery and can be continued no earlier than 48 hours after, provided that during the examination the kidney function was recognized normal. Administration of the drug Metadien should be discontinued 48 hours before and not resumed earlier than 2 days after radiologic examination using iodine-containing radiopaque agents, provided that during the examination the kidney function was normal.

Because the metformin it is necessary to determine the content and / or clearance of creatinine (CC) in the blood serum: 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 QC at the lower limit of the norm.Therapy with the drug Metadien is recommended to begin after evaluation of kidney function. With a decrease in QC kidney function should be monitored at least 2-4 times a year.

Special care should be taken in the event of a possible impairment of kidney function in elderly patients, with the simultaneous use of antihypertensive drugs, diuretics or NSAIDs.

The patient should inform the doctor about the appearance of a broncho-pulmonary infection or an infectious disease of the genito-urinary organs.

Regular laboratory tests should be performed regularly to monitor diabetes mellitus.

When taking the drug, avoid drinking alcohol and medications containing ethanol.

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

Monotherapy with Metadien does not cause hypoglycemia, and therefore does not affect the ability to drive vehicles and work with mechanisms.

When using Metadiene with other hypoglycemic agents (derivatives of sulfonylurea, insulin, etc.), it is possible to develop hypoglycemic conditions in which the ability to drive vehicles and engage in other potentially hazardous activities deteriorates,require increased attention and rapid psychomotor reactions.

Form release / dosage:Long-acting tablets 500 mg.

Packaging:For 10 tablets in an aluminum blister. 10 the blister pack in a cardboard, together with instructions for use.

Storage conditions:List B. Store 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005999/10

Date of registration:25.06.2010

Expiration Date:Unlimited

The owner of the registration certificate:Vokhard LtdVokhard Ltd India

Manufacturer: & nbsp

WOCKHARDT, Ltd. India

Representation: & nbspVokhard Ltd., IndiaVokhard Ltd., India

Information update date: & nbsp07.05.2018

Illustrated instructions

Instructions

Metadiene (Metadien)