Formetin Long, 1000 mg 60 pcs

Pharmacotherapeutic group:

Hypoglycemic oral drug of the biguanide group

ATC:

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin is a biguanide with hypoglycemic action 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 receptors to insulin and glucose utilization by cells. Reduces glucose production by the liver by inhibiting gluconeogenesis and glycogenolysis. Delays glucose absorption in the intestine. Metformin stimulates glycogen synthesis by acting on glycogen synthase. Increases the transport capacity of all types of membrane glucose transporters. Against the background of metformin administration, the patient’s body weight either remains stable or decreases moderately.

Metformin has a favorable effect on lipid metabolism: it reduces total cholesterol, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Intake

After oral administration of the drug in the form of sustained-release tablets, metformin absorption is delayed compared to tablets with normal metformin release.

The time to reach the maximum Cmax concentration at the average value is 5-7 hours (range from 4 to 12 hours). At the same time, the TCmax for the tablet with normal release is 2.5 hours.

In the equilibrium state, identical to the equilibrium state of metformin with normal release, the maximum concentration (Cmax) and the area under the curve “concentration-time” (AUC) increase not in proportion to the dose taken. After a single oral dose of 2000 mg of metformin in the form of sustained release tablets, the AUC is similar to that observed after taking 1000 mg of metformin in the form of normally-released tablets twice daily. Intraindividual variability of Cmax and AUC after administration of metformin in the form of sustained release tablets is similar to that observed after administration of metformin in the form of normally-released tablets.

The absorption of metformin from sustained release tablets does not vary with food intake. No cumulation is observed with repeated administration of up to 2000 mg of metformin in the form of sustained release tablets.

Distribution

The binding to plasma proteins is insignificant. Cmax in blood is lower than Cmax in plasma and is reached after approximately the same time. Mean volume of distribution (Vd) ranges from 63-276 L.

Metabolism

Metabolites have not been detected in humans.

Elimination

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. In impaired renal function, metformin clearance decreases in proportion to creatinine clearance, the elimination half-life increases, which may lead to increased plasma concentrations of metformin.

Indications

Type 2 diabetes mellitus in adults, especially in obese patients, with ineffective diet therapy and exercise:

– as monotherapy;

– in combination with other oral hypoglycemic agents or insulin.

Pharmacological effect

Pharmacotherapeutic group:

Hypoglycemic agent for oral administration of the biguanide group

ATX:

A.10.B.A.02 Metformin

Pharmacodynamics:

Metformin is a biguanide with a hypoglycemic effect, reducing both basal and postprandial plasma glucose concentrations. It does not stimulate insulin secretion and therefore does not cause hypoglycemia. Increases the sensitivity of peripheral receptors to insulin 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, low-density lipoproteins and triglycerides.

Pharmacokinetics:

Suction

After oral administration of the drug in the form of extended-release tablets, the absorption of metformin is slower compared to regular-release tablets of metformin.

The time to reach the maximum concentration Cmax at an average value is 5-7 hours (range from 4 to 12 hours). At the same time, the TCmax for a regular-release tablet is 2.5 hours.

At steady state, identical to that of regular-release metformin, the maximum concentration (Cmax) and the area under the concentration-time curve (AUC) increase disproportionately to the dose taken. Following a single oral dose of 2000 mg metformin extended-release tablets, the AUC is similar to that observed after dosing 1000 mg metformin regular-release tablets twice daily. Intra-individual variability in Cmax and AUC following administration of metformin extended-release tablets is similar to that observed after administration of metformin regular-release tablets.

The absorption of metformin from extended-release tablets is not affected by food intake. No accumulation is observed with repeated doses of up to 2000 mg of metformin in the form of extended-release tablets.

Distribution

Communication with plasma proteins is negligible. Cmax in the blood is lower than Cmax in plasma and is reached after approximately the same time. The average volume of distribution (Vd) ranges from 63-276 l.

Metabolism

No metabolites have been detected in humans.

Removal

Metformin is excreted unchanged by the kidneys.

The renal clearance of metformin is >400 ml/min, indicating that metformin is eliminated by glomerular filtration and tubular secretion. After oral administration, the half-life is approximately 6.5 hours. With impaired renal function, the clearance of metformin decreases in proportion to the clearance of creatinine, the half-life increases, which can lead to an increase in the concentration of metformin in plasma.

Special instructions

Lactic acidosis

Lactic acidosis is a rare but serious (high mortality unless promptly treated) complication that may occur due to accumulation of metformin. Cases of lactic acidosis when taking metformin occurred mainly in patients with diabetes mellitus with severe renal failure.

Other associated risk factors should be taken into account, such as decompensated diabetes mellitus, ketosis, prolonged fasting, alcoholism, liver failure and any condition associated with severe hypoxia. This may help reduce the incidence of lactic acidosis.

The risk of developing lactic acidosis should be taken into account when nonspecific signs appear, such as muscle cramps accompanied by dyspeptic disorders, abdominal pain and severe asthenia.

Lactic acidosis is characterized by severe malaise with general weakness, acidotic shortness of breath, vomiting, abdominal pain, muscle cramps and hypothermia followed by coma. Diagnostic laboratory parameters are a decrease in blood pH (less than 7.25), plasma lactate concentration over 5 mmol/l, increased anion gap and lactate/pyruvate ratio. If lactic acidosis is suspected, stop taking the drug and consult a doctor immediately.

Surgical operations

The use of metformin should be discontinued 48 hours before elective surgery and can be continued no earlier than 48 hours after, provided that renal function has been 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 creatinine clearance: 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.

Particular caution should be exercised in case of possible impairment of renal function in elderly patients, with simultaneous use of antihypertensive drugs, diuretics or non-steroidal anti-inflammatory drugs.

Heart failure

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

Other precautions:

– Patients are advised to continue to follow a diet with even carbohydrate intake throughout the day. Overweight patients are advised 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 treatment being carried out and any infectious diseases such as colds, respiratory tract infections or urinary tract infections;

– it is recommended to regularly carry out standard laboratory tests to control diabetes mellitus;

– metformin in monotherapy does not cause hypoglycemia, however, it is recommended to exercise caution when using it in combination with insulin or other oral hypoglycemic agents (for example, sulfonylurea derivatives or repaglinide, etc.). Symptoms of hypoglycemia include weakness, headache, dizziness, increased sweating, rapid heartbeat, blurred vision, or difficulty concentrating;

– it is necessary to warn the patient that the inactive components of the drug Formetin® 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 lactose. The drug is contraindicated in patients with lactose intolerance, lactase deficiency, and glucose-galactose malabsorption.

Impact on the ability to drive vehicles. Wed and fur.:

Monotherapy with Formetin® Long does not cause hypoglycemia, and therefore does not affect the ability to drive vehicles and machines. However, it is possible to develop hypoglycemia when using metformin in combination with other hypoglycemic drugs (sulfonylurea derivatives, insulin, repaglinide, etc.). If symptoms of hypoglycemia appear, you should not drive vehicles or machinery.

Active ingredient

Metformin

Composition

For one tablet:

Active ingredient: metformin hydrochloride – 500.00 mg, 750.00 mg, 850.00 mg, 1000.0 mg.

Excipients: hypromellose (hydroxypropyl methylcellulose 200,000 cP) – 248.00 mg, 330.00 mg, 374.00 mg, 294.00 mg; hyprolose (hydroxypropylcellulose) – 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; colloidal silicon dioxide (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.

Shell: VIVACOAT® PA-1P-000 [hypromellose (hydroxypropyl methylcellulose 6 cP) – 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.

Contraindications

– Hypersensitivity to metformin or to any excipient;

– diabetic ketoacidosis, diabetic precoma, coma;

– renal failure or impaired renal function (creatinine clearance less than 45 ml/min);

– acute conditions with a risk of developing renal dysfunction: dehydration (with chronic or severe diarrhea, repeated bouts of vomiting), severe infectious diseases (for example, respiratory tract 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 operations and injuries, when insulin therapy is indicated (see section “Special instructions”);

– liver failure, liver dysfunction;

– chronic alcoholism, acute alcohol poisoning;

– pregnancy;

– lactic acidosis (including history);

– use for less than 48 hours before and within 48 hours after radioisotope or x-ray studies with the introduction of iodine-containing contrast agent (for example, internal urography, angiography) (see section “Interaction with other drugs”);

– adherence to a hypocaloric diet (less than 1000 cal/day);

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

– children under 18 years of age due to the lack of data on use.

With caution:

Use 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 failure (creatinine clearance 45-59 ml/min)

– during breastfeeding.

Side Effects

The frequency of side effects of the drug is assessed as follows:

Very common: ≥ 1/10.

Frequent: ≥ 1/100, < 1/10.

Uncommon: ≥ 1/1000, < 1/100.

Rare: ≥ 1/10,000, < 1/1000.

Very rare: <1/10,000.

Metabolic and nutritional disorders:

Very rare: lactic acidosis (see “Special Instructions”).

With long-term use of metformin, a decrease in the absorption of vitamin B12 may be observed. When megaloblastic anemia is detected, the possibility of such an etiology must be taken into account.

Nervous system disorders:

Common: taste disturbance (metallic taste in the mouth).

Gastrointestinal disorders:

Very common: nausea, vomiting, diarrhea, abdominal pain and lack of appetite.

Most often they occur during the initial period of treatment and in most cases resolve spontaneously. To prevent symptoms, it is recommended to take metformin with meals. Slowly increasing the dose may improve gastrointestinal tolerability.

Disorders of the liver and biliary tract:

Very rare: abnormal liver function tests and hepatitis; after discontinuation of metformin, these adverse effects completely disappear.

Disorders of the skin and subcutaneous tissues:

Very rare: skin reactions such as erythema (redness of the skin), itching, urticaria.

If any of the side effects indicated in the instructions get worse, or any other side effects not listed in the instructions are noticed, you should inform your doctor.

Interaction

Contraindicated combinations

Iodine-containing radiocontrast agents: against the background of functional renal failure in patients with diabetes mellitus, radiological examination using iodine-containing X-ray contrast agents can cause the development of lactic acidosis. Taking Formetin® Long should be discontinued depending on renal function 48 hours before or during an X-ray examination using iodine-containing radiocontrast agents and resumed no earlier than 48 hours after, provided that during the examination renal function was found to be normal.

Combinations not recommended

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

– insufficient nutrition, adherence to a low-calorie diet;

– liver failure.

While taking the drug, you should avoid drinking alcohol and medications containing ethanol.

Combinations requiring caution

Medicines with indirect hyperglycemic effects (for example, glucocorticosteroids (GCS) and tetracosactide (systemic and local), beta2-agonists, danazol, chlorpromazine when taken in large doses (100 mg per day) and diuretics: more frequent monitoring of blood glucose concentrations may be required, especially at the beginning of treatment. If necessary, the dose of Formetin® Long can be adjusted during treatment and after its termination, based on the level of glycemia.

Diuretics: Concomitant use of loop diuretics may lead to the development of lactic acidosis due to possible functional renal failure. Formetin® Long should not be prescribed if creatinine clearance is less than 45 ml/min.

With simultaneous use of the drug Formetin® Long with sulfonylurea derivatives, insulin, acarbose, and salicylates, hypoglycemia may develop.

Nifedipine increases 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 may lead to an increase in its Cmax.

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

Overdose

When using metformin at a dose of 85 g (42.5 times the maximum daily dose), no hypoglycemia was observed. However, in this case, the development of lactic acidosis was observed. Significant overdose or associated risk factors can lead to the development of lactic acidosis (see “Special Instructions”).

Treatment: if signs of lactic acidosis appear, treatment with the drug must be stopped immediately, the patient must be urgently hospitalized and, having determined the lactate concentration, the diagnosis must be clarified. The most effective measure for removing lactate and metformin from the body is hemodialysis. Symptomatic treatment is also carried out.

Storage conditions

Store at a temperature not exceeding 25 °C.
Keep out of the reach of children.

Shelf life

2 years.

Manufacturer

Pharmstandard-Leksredstva, Russia