Merifatin MB sustained release pills 500mg, 60pcs

Composition

Per tablet:

Active ingredient:  metformin hydrochloride – 500 mg.

Auxiliary substances:  hypromellose 2208-256.0 mg; carmellose sodium (carboxymethylcellulose sodium) – 28.0 mg; giprolose (hydroxypropylcellulose) – 10.0 mg; copovidone-2.0 mg; magnesium stearate-4.0 mg

Pharmacological action

Metformin is a hypoglycemic biguanide that reduces both basal and postprandial plasma glucose concentrations. It does not stimulate insulin secretion and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral insulin receptors and the utilization of glucose by cells. Reduces liver glucose production by inhibiting gluconeogenesis and glycogenolysis. Delays the absorption of glucose in the intestines.

Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters.

While taking metformin, the patient’s body weight either remains stable or decreases moderately. Metformin has a beneficial effect on lipid metabolism: it reduces the content of total cholesterol, LDL (low-density lipoproteins) and triglycerides. Pharmacokinetics:

Absorption rate

After a single dose of metformin with a prolonged release (500 mg and 750 mg long-release tablets) at a dose of 1500 mg, the average time to reach the maximum concentration of metformin in blood plasma (Tmax) is 5 hours (in the range of 4-12 hours). After a single dose of 1 tablet of metformin with a prolonged release in a dosage of 1000 mg after a meal, the average Tmax is 5 hours (in the range of 4-10 hours).

At steady state, identical to the steady state of metformin with normal release, the maximum concentration (Cmax) and area under the concentration-time curve (AUC) increase out of proportion to the dose taken. The AUC after a single 2000 mg extended-release metformin dose is similar to that observed after a normal 1000 mg twice-daily metformin dose.

Intra-individual variability in Cmax and AUC after taking metformin in the form of extended-release tablets is similar to that observed after taking metformin with a normal release.

After a single 1000 mg extended-release metformin dose after a meal, AUC increases by 77%, Cmax increases by 26%, and TMAX increases by approximately 1 h. The absorption of metformin with prolonged release does not change depending on the composition of the food taken.

No accumulation is observed with repeated use of metformin with prolonged release at a dose of up to 2000 mg.

Distribution

Metformin is rapidly distributed in tissues, practically does not bind to plasma proteins, and is able to accumulate in red blood cells. Cmax in blood is lower than Cmax in blood plasma and is reached in approximately the same time. The average volume of distribution is 63-276 liters.

Metabolism

It is metabolized to a very weak degree, and no metabolites are found in the body.

Deduction

It is excreted unchanged by the kidneys. The clearance of metformin in healthy volunteers is more than 400 ml / min (4 times higher than creatinine clearance), which indicates the presence of active tubular secretion.

The elimination half-life is approximately 6.5 hours.

Impaired renal function

With impaired renal function, metformin clearance decreases in proportion to creatinine clearance( CC), respectively, the half-life increases, the concentration of metformin in blood plasma increases, and the risk of its accumulation increases.

Indications

Type 2 diabetes mellitus in adults (especially in obese patients) with ineffective diet therapy and physical activity:

• as monotherapy;
• in combination with other oral hypoglycemic agents or with insulin.

Contraindications

– Hypersensitivity to Metformin or to any accessory ingredient;

– diabetic ketoacidosis, diabetic precoma, coma;

renal failure or impaired renal function (CC less than 30 ml/min);

acute condition of proceeding with the risk of developing renal dysfunction: dehydration (chronic or severe diarrhea, repeated vomiting), severe infection (e. g., respiratory tract infections, urinary tract infections), shock;

– symptomatic manifestations of acute or chronic diseases which can lead to the development of tissue hypoxia (including acute heart failure, chronic heart failure with unstable hemodynamic, respiratory failure, acute myocardial infarction);

– extensive surgery and trauma, when shown holding insulin (see “Special instructions”);

– liver failure, liver dysfunction;

chronic alcoholism, acute alcohol intoxication;

– pregnancy;

– lactic acidosis (including history);

– application in less than 48 hours before and within 48 hours after the radioisotope or radiological examinations with use of iodinated contrast agents (eg, IV urography, angiography) (see “Interaction with other medicines”);

– adherence to a reduced-calorie diet (<1000 cal/day);

the age of 18 (due to the lack of data on efficacy and safety of use in this age group).

With caution:

– In patients 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 30-59 ml/min);

– During breastfeeding.

Side effects

Classification of the incidence of HP when using the drug according to the recommendations of the World Health Organization (WHO): very common (≥1/10); common (≥ 1/100, <1/10); infrequent (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (

From the side of metabolism:  very rarely – lactic acidosis.

With prolonged use of metformin, there may be a decrease in the absorption of vitamin B12. If megaloblastic anemia is detected, it is necessary to consider the possibility of such an etiology.

Nervous system disorders:  often-a violation of taste (metallic taste in the mouth).

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 pass spontaneously. To prevent symptoms, it is recommended to take metformin during or after a meal. Slowly increasing the dose may improve gastrointestinal tolerance.

Liver and biliary tract disorders:  very rarely – impaired liver function and hepatitis; after discontinuation of the drug, these symptoms completely disappear.

Skin and subcutaneous tissue disorders:  very rarely-skin reactions such as erythema (redness of the skin), pruritus, urticaria.

If any of the HPV listed in the instructions get worse or if other HPV’s appear that are not listed in the instructions, you should inform your doctor.

Interaction

Contraindicated combinations

of iodine-containing radiopaque agents:  against the background of functional renal failure in patients with diabetes mellitus, radiological examination with the use of iodine-containing radiopaque agents can cause the development of lactic acidosis. Depending on renal function, metformin should be discontinued 48 hours before or for the duration of an X-ray examination using iodine-containing radiopaque agents, and resumed no earlier than 48 hours after, provided that renal function was found to be normal during the examination.

Not recommended combinations

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

– insufficient nutrition, compliance with a low-calorie diet;

– liver failure.

During therapy with the drug, you should stop drinking alcohol and taking medications containing ethanol.

Combinations that require caution

Drugs with indirect hyperglycemic effects (for example, corticosteroids (systemic and local action) and tetracosactide, beta-2-adrenomimetics, danazol, chlorpromazine when taken in large 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 Merifatin MV can be adjusted during treatment and after its termination, based on the level of glycemia.

Diuretics: concomitant use of loop diuretics may lead to lactic acidosis due to possible functional renal failure.

Concomitant use of Merifatin MV with sulfonylurea derivatives, insulin, acarbose, and salicylates may lead to hypoglycemia.

Nifedipine increases the absorption and Cmax of metformin.

Cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim, and vancomycin) secreted in the renal tubules compete with metformin for tubular transport systems and can lead to an increase in its Cmax.

Colesevelam, when used concomitantly with metformin in the form of long-release tablets, increases the concentration of metformin in blood plasma (increases AUC without a significant increase in Cmax).

Oral contraceptives, epinephrine, glucagon, thyroid hormones, phenothiazine derivatives, nicotinic acidthe hypoglycemic effect of metformin can be reduced by phenothiazides, glucagon, estrogens, oral contraceptives, phenytoin, sympathomimetics, nicotinic acid, isoniazid, slow calcium channel blockers, levothyroxine sodium.

Concomitant use with cimetidine reduces the rate of elimination of metformin, which can lead to the development of lactic acidosis.

In healthy volunteers, no changes in their pharmacokinetic parameters were observed when metformin and propranolol were co-administered, as well as when metformin and ibuprofen were used.

Metformin may reduce the effect of indirect anticoagulants.

Substrates of organic cation transporter 1 and 2 (OST 1 and OST 2)

Metformin is a substrate of organic cations OST 1 and OST 2.

When combined with metformin:

• OST 1 inhibitors (such as verapamil) may reduce the hypoglycemic action of Metformin;
• inductors OST 1 (such as rifampicin) may increase the absorption of Metformin in the gastrointestinal tract and enhance its hypoglycemic effect;
• inhibitors OST 2 (such as cimetidine, dolutegravir, ranolazine, trimethoprim, vandetanib, isavuconazole) may reduce the excretion of Metformin by the kidneys and lead to an increase in its concentration in blood plasma;
• inhibitors OST 1 and OST 2 (such as krizotinib, olaparib) may reduce the hypoglycemic effect of Metformin.

How to take, course of use and dosage

Inside. Tablets are swallowed whole, without chewing, with a small amount of liquid,1 time / day during dinner.

The dose of Merifatin MV is selected by the doctor individually for each patient based on the results of determining the concentration of blood glucose.

Adult patients with normal renal function (creatinine clearance ≥ 90 ml / min)

Monotherapy and combination therapy in combination with other hypoglycemic agents

-Merifatin MV at a dose of 1000 mg should be taken once a day (once/day) during dinner.

– Merifatin MB 1000 mg is prescribed as maintenance therapy for patients taking metformin with a normal release at a dose of 1000 mg or 2000 mg. To switch to Merifatin MV 1000 mg, the daily dose of metformin should be equivalent to the daily dose of metformin with a normal release. – Patients taking metformin in the form of tablets with a normal release at a dose exceeding 2000 mg are not recommended to switch to Merifatin MV at a dose of 1000 mg. – For patients who do not take metformin, the recommended starting dose of Merifatin MB is 500 mg or 750 mg once a day, with dinner. Every 10-15 days, it is recommended to adjust the dose based on the results of determining the blood glucose concentration. A slow increase in the dose helps to reduce side effects from the gastrointestinal tract (GIT).

– In the case of switching from another hypoglycemic agent, the dose selection is carried out as described above, starting with the appointment of Merifatin MV at a dose of 500 mg or 750 mg, with a possible subsequent transition to Merifatin MV at a dose of 1000 mg.

Combination with insulin

To achieve better blood glucose control, metformin and insulin can be used as a combination therapy. The usual starting dose of Merifatin MV is 1 tablet of 500 mg once a day or 750 mg once a day during dinner, while the dose of insulin is selected based on the results of determining the concentration of blood glucose. Then you can switch to the drug Merifatin MV in a dose of 1000 mg.

Daily dose

The maximum recommended dose of Merifatin MV is 4 tablets of 500 mg per day (2000 mg) or 3 tablets of 750 mg per day (2250 mg) or 2 tablets of 1000 mg per day (2000 mg).

If the maximum recommended dose of 1 time/day during dinner fails to achieve adequate glycemic control, then the maximum dose can be divided into two doses: 2 500 mg tablets – during breakfast and 2 500 mg tablets – during dinner, or one 1000 mg tablet – during breakfast and one 1000 mg tablet – during dinner.

If adequate glycemic control is not achieved when taking the maximum recommended dose of Merifatin MV tablets with a prolonged release, it is possible to switch to metformin with a normal release of the Active ingredient with a maximum daily dose of 3000 mg.

Use of the drug in special clinical groups of patients

Skipping a dose

If the next dose is missed, the next dose should be taken at the usual time. Do not take a double dose of Merifatin MV.

Patients with renal insufficiency

Metformin can be used in patients with renal insufficiency creatinine clearance 30 – 59 ml/min only in the absence of conditions/risk factors that may increase the risk of lactic acidosis.

Elderly patients

Due to a possible decrease in renal function, the metformin dose is adjusted based on a regular assessment of renal function.

Children and teenagers under 18 years of age

The use of the drug is contraindicated in children and adolescents under 18 years of age (due to the lack of clinical data on efficacy and safety).

Duration of treatment

Merifatin MV should be taken daily, without interruption. If treatment is discontinued, the patient should inform the doctor.

Renal function should be carefully monitored: creatinine clearance should be determined every 3-6 months in patients with creatinine clearance of 45-59 ml/min and every 3 months with creatinine clearance of 30-44 ml/min.

If creatinine clearance is below 30 ml/min, metformin should be discontinued immediately.

Overdose

When metformin was administered at a dose of up to 85 g (42.5 times the maximum daily dose), no episodes of hypoglycemia were observed. However, in this case, the development of lactic acidosis was observed. Significant overdose or associated risk factors can lead to lactic acidosis.

Symptoms of lactic acidosis are: severe weakness, myalgia, abdominal pain, respiratory disorders, increased drowsiness. In severe lactic acidosis, the development of arterial hypotension and resistant bradyarrhythmia was noted.

Treatment: in case of signs of lactic acidosis, the drug should be stopped immediately, the patient should be urgently hospitalized and, after determining the lactate concentration, the diagnosis should be clarified. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also performed.

Special instructions

Lactic acidosis

Lactic acidosis is a rare but serious complication (high mortality in the absence of urgent treatment) that can occur due to the accumulation of metformin. Cases of lactic acidosis during metformin use occurred mainly in patients with diabetes mellitus with severe renal insufficiency.

Other associated risk factors should also be considered, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure, and any condition associated with severe hypoxia, severe infectious disease, and concomitant use with certain medications. This can help reduce the incidence of lactic acidosis.

The risk of developing lactic acidosis should be considered if there are non-specific signs, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain, and severe asthenia.

Lactic acidosis is characterized by severe malaise with general weakness, acidotic dyspnea and vomiting, abdominal pain, muscle cramps, and hypothermia followed by coma. Diagnostic laboratory parameters are a decrease in blood pH (less than 7.35), a concentration of lactate in blood plasma over 5 mmol / l, an increased anion gap and the ratio of lactate/pyruvate. If lactic acidosis is suspected, stop taking the drug and immediately consult a doctor.

Intravascular use of iodine-containing radiopaque agents can lead to the development of renal failure and accumulation of metformin, which increases the risk of lactic acidosis. Metformin should be discontinued, depending on renal function,48 hours before or during an X-ray examination using iodine-containing radiopaque agents, and not resumed earlier than 48 hours after it, provided that during the examination the renal function was found to be normal.

Surgical operations

The use of metformin should be discontinued 48 hours before elective surgery and may be continued no earlier than 48 hours after, provided that renal function was found to be normal during the examination.

Kidney function

Since metformin is excreted by the kidneys, before starting treatment and regularly thereafter, it is necessary to determine the content and/or creatinine clearance in 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 creatinine clearance at the lower limit of normal.

Special care should be taken in case of possible impairment of renal function in elderly patients, while using antihypertensive drugs, diuretics or nonsteroidal anti-inflammatory drugs.

In case of dehydration (chronic or severe diarrhea, repeated attacks of vomiting).

Heart failure

Patients with heart failure have a higher risk of developing hypoxia and kidney failure.Patients with chronic heart failure should be regularly monitored for cardiac renal function while taking metformin. Metformin is contraindicated in patients with acute heart failure and chronic heart failure with unstable hemodynamic parameters.

Other precautions

-Patients are advised to continue to follow a diet with a uniform intake of carbohydrates throughout the day. Overweight patients are recommended to continue to follow a hypocaloric diet (but not less than 1000 kcal / day). Patients should also exercise regularly.

– Patients should inform the doctor about any ongoing treatment and any infectious diseases, such as colds, respiratory or urinary tract infections.

– It is recommended to regularly perform standard laboratory tests to control diabetes mellitus.

– Metformin alone does not cause hypoglycemia, but caution is recommended when used in combination with insulin or other oral hypoglycemic agents (for example, sulfonylureas or repaglinide, etc. ). Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, visual impairment or impaired concentration.

– It is necessary to warn the patient that the excipients of Merifatin MV may be excreted unchanged through the intestine, which does not affect the pharmacological effect of the drug.

Influence on the ability to drive vehicles and mechanisms:Monotherapy with Merifatin MV does not cause hypoglycemia, so it does not affect the ability to drive vehicles and mechanisms. However, hypoglycemia may occur when metformin is used in combination with other hypoglycemic drugs (sulfonylureas, insulin, repaglinide, etc. ). If symptoms of hypoglycemia occur, do not drive vehicles or mechanisms.

Storage conditions

Store in a dark place, at a temperature not exceeding 25°C.

Keep out of the reach of children.

Shelf

life is 3 years.

Do not use after the expiration date.

Active ingredient

Metformin

Conditions of release from pharmacies

By prescription

Dosage form

long-acting tablets