FOGLI 500/2.5 [Metformin hydrochloride + Glimepiride] 500 + 2.5 mg Film-coated tablets
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FOGLI
instructions for medical use of the medicinal product
Tradename
Fogli, Фогли
International non-proprietary name
Metformin hydrochloride + Glimepiride,
Composition
Each film-coated tablet contains:
active substances: metformin hydrochloride 500 mg, glimepiride 2.5 mg
excipients: starch, dextrin, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium starch glycolate, silicon dioxide, magnesium stearate, talc
Each film-coated tablet contains:
active substances: metformin hydrochloride 500 mg, glimepiride 5 mg
excipients: starch, dextrin, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium starch glycolate, silicon dioxide, magnesium stearate, talc
Each film-coated tablet contains:
active substances: metformin hydrochloride 1000 mg, glimepiride 5 mg
excipients: starch, dextrin, microcrystalline cellulose, hydroxypropyl methylcellulose, sodium starch glycolate, silicon dioxide, magnesium stearate, talc
Dosage form
Tablets.
Pharmacotherapeutic group
Antidiabetic drugs. Combination of oral hypoglycemic drugs.
Pharmacological properties
Pharmacodynamics
metformin hydrochloride
It reduces the absorption of glucose from the intestine and enhances its peripheral utilization, increasing the sensitivity of tissues to insulin, and inhibits gluconeogenesis in the liver. Reduces the level of low density lipoproteins and triglycerides in blood plasma. Does not cause hypoglycemic reactions, does not affect the secretion of insulin by β -cells of the pancreas. Due to the suppression of the tissue plasminogen activator inhibitor, it has a fibrinolytic effect. Stabilizes or reduces body weight.
Glimepiride
A third-generation sulfonylurea derivative, by lowering the threshold of irritation of pancreatic β-cells with glucose, stimulates insulin secretion, increases its release and the degree of binding to target cells. The hypoglycemic effect depends on the number of functioning β-cells.
Suppresses platelet aggregation, has a fibrinolytic, hypolipidemic and weak diuretic effect.
Pharmacokinetics
metformin hydrochloride
After oral administration, up to 50-60% is absorbed in the gastrointestinal tract. The maximum plasma concentration is reached after 2.5 hours. Does not bind to plasma proteins.
Accumulates in muscle tissue, salivary glands, kidneys and liver.
The half-life is 6 hours. Elimination by the kidneys unchanged.
Glimepiride
After oral administration, it is completely absorbed in the gastrointestinal tract. The maximum plasma concentration is reached after 2-3 hours. Communication with plasma proteins is more than 99%.
The therapeutic effect develops 60-90 minutes after ingestion and lasts for 24 hours. Metabolism in the liver by oxidation to a cyclomethyl derivative (possesses 30% of the activity of the parent substance), which subsequently turns into an inactive metabolite. Does not accumulate.
The half-life is 5-8 hours. Elimination by the kidneys and with faeces as metabolites.
Indications for use
As an adjunct to diet and exercise for people with type 2 diabetes mellitus:
· if monotherapy with sulfonylureas or metformin hydrochloride does not provide an adequate level of glycemic control;
· when replacing combination therapy with sulfonylureas and metformin hydrochloride.
Contraindications
· Type I diabetes mellitus;
· diabetic ketoacidosis (including history), diabetic coma and precoma;
· acute or chronic metabolic acidosis;
· severe liver dysfunction (lack of experience with use; insulin treatment is necessary to ensure adequate glycemic control);
· patients on hemodialysis (lack of experience with use);
· renal failure and impaired renal function (plasma creatinine concentration ≥1.5 mg / dl (135 μmol / l) in men and ≥1.2 mg / dl (110 μmol / l) in women or a decrease in CC (increased risk of developing lactic acidosis and other side effects of metformin hydrochloride);
· acute conditions in which renal dysfunction is possible (dehydration, severe infections, shock, intravascular administration of iodine-containing contrast agents);
· acute and chronic diseases that can cause tissue hypoxia (cardiac or respiratory failure, acute and subacute myocardial infarction, shock);
· a tendency to develop lactic acidosis, a history of lactic acidosis;
· stressful situations (severe injuries, burns, surgeries, severe infections with fever, septicemia);
· exhaustion, starvation, compliance with a hypocaloric diet (less than 1000 cal / day);
· impaired absorption of food and drugs in the gastrointestinal tract (with intestinal obstruction, intestinal paresis, diarrhea, vomiting);
· chronic alcoholism, acute alcohol intoxication;
· lactase deficiency, galactose intolerance, glucose-galactose malabsorption;
· pregnancy, pregnancy planning;
· breastfeeding period;
· children and adolescents under 18 years of age (insufficient clinical experience);
· hypersensitivity to the components of the drug;
· hypersensitivity to sulfonylurea derivatives, sulfanilamide drugs or biguanides.
Dosage and administration
Taken orally, before or during a meal. Tablets are swallowed whole, without chewing, drinking plenty of water.
The dose and duration of taking an antidiabetic drug is set individually depending on the patient's blood glucose level. As a rule, it is recommended to start treatment with the minimum effective dose and increase the dose of the drug depending on the level of glucose in the patient's blood. The drug is used exclusively in adults, 1 or 2 times a day.
The maximum dose of metformin hydrochloride per dose is 1000 mg. The maximum daily dose: for glimepiride - 8 mg, for metformin hydrochloride - 2000 mg.
Only in a small number of patients is more effective daily dose of glimepiride more than 6 mg.
In order to avoid the development of hypoglycemia, the initial dose should not exceed the daily doses of metformin hydrochloride and glimepiride that the patient is already taking. When transferring patients from taking a combination of separate drugs of metformin hydrochloride and glimepiride to this combination, its dose is determined on the basis of the doses of metformin hydrochloride and glimepiride already taken as separate drugs.
Errors in the use of the drug, such as skipping the next dose, can never be corrected by the subsequent intake of a higher dose.
Special instructions and precautions
With caution, the drug should be prescribed to patients over 65 years of age due to a decrease in kidney function. Before the appointment of the drug Fogli, as well as every 6 months, it is necessary to monitor the functions of the liver and kidneys. It is necessary to control the level of lactate in the blood at least 2 times a year. The drug should be replaced with another hypoglycemic drug (for example, insulin) 2 days before X-ray examination with intravenous contrast agents, as well as 2 days before surgery under general anesthesia and continue for another 2 days after this examination or operation. In extremely rare cases (with an overdose of the drug, in the presence of concomitant diseases, with alcoholism), lactic acidosis may develop. The results of clinical studies aimed at studying the hypotensive effect of metformin hydrochloride indicate that the drug affects the daily blood pressure profile in patients with clinical manifestations of metabolic (insulin resistant) syndrome X. The hypotensive effect of metformin hydrochloride is most likely directly related to a decrease in insulin resistance and hyperinsulinemia, playing an important role in the activity of the sympathetic-adrenal system.
Influence on the ability to drive vehicles and mechanisms
Use during pregnancy and during breastfeeding
Contraindicated in pregnancy and during breastfeeding .
Interaction with other drugs
With drugs that enhance the hypoglycemic effect of metformin hydrochloride: insulin, sulfonylurea drugs, anabolic steroids, guanethidine, salicylates (including acetylsalicylic acid), beta-blockers (including propranolol), MAO inhibitors: in the case of simultaneous use of these drugs with metformin hydrochloride, careful monitoring of the patient and monitoring of blood glucose concentrations are necessary, since it is possible to increase the hypoglycemic effect of metformin hydrochloride.
With drugs that weaken the hypoglycemic effect of metformin hydrochloride: epinephrine, corticosteroids, thyroid hormones, estrogens, pyrazinamide, isoniazid, nicotinic acid, phenothiazines, thiazide diuretics and diuretics of other groups, oral contraceptives, phenytoin, sympathomimetics, slow calcium channel blockers: in the case of the simultaneous use of these drugs with metformin, careful monitoring of the patient and monitoring of blood glucose concentrations are necessary, tk. possible weakening of the hypoglycemic effect.
With furosemide: in a clinical study on the interaction of metformin hydrochloride and furosemide when taken once in healthy volunteers, it was shown that the simultaneous use of these drugs affects their pharmacokinetic parameters. Furosemide increased Cmax of metformin hydrochloride in blood plasma by 22%, a AUC by 15% without any significant change in the renal clearance of metformin hydrochloride. When used with metformin hydrochloride, Cmax and AUC of furosemide decreased by 31% and 12%, respectively, compared with furosemide monotherapy, and terminal T 1/2 decreased by 32% without any significant change in the renal clearance of furosemide. There is no information on the interaction of metformin hydrochloride and furosemide with long-term use.
With nifedipine: in a clinical study of the interaction of metformin hydrochloride and nifedipine when taken once in healthy volunteers, it was shown that the simultaneous use of nifedipine increases the Cmax and AUC of metformin hydrochloride in blood plasma by 20% and 9%, respectively, and also increases the amount of metformin hydrochloride excreted by the kidneys. Metformin hydrochloride had minimal effect on the pharmacokinetics of nifedipine.
With cationic drugs (amiloride, digoxin, morphine, procainamide, quinidine, quinine, ranitidine, triamterene, trimethoprim and vancomycin): cationic drugs excreted by tubular secretion in the kidneys are theoretically able to interact with metformin hydrochloride as a result of competition for a common tubular transport system. This interaction between metformin hydrochloride and oral cimetidine was observed in healthy volunteers in single and multiple dose clinical interaction studies of metformin hydrochloride and cimetidine, where there was a 60% increase in plasma Cmax and total metformin hydrochloride concentration in the blood and a 40% increase in plasma and total AUC of metformin. hydrochloride. With a single acceptance of changes T 1/2 did not have. Metformin hydrochloride did not affect the pharmacokinetics of cimetidine. Although such an interaction remains purely theoretical (with the exception of cimetidine), careful monitoring of patients and dose adjustment of metformin hydrochloride and / or the drug interacting with it should be carried out in case of simultaneous use of cationic drugs excreted from the body by the secretory system of the proximal tubules of the kidneys .
With iodinated contrast agents: intravascular administration of iodine-containing contrast agents can lead to the development of renal failure, which in turn can lead to the accumulation of metformin hydrochloride and an increased risk of lactic acidosis. Metformin hydrochloride should be discontinued before or during the study and not resumed within 48 hours after it; resuming metformin hydrochloride is possible only after examination and obtaining normal indicators of kidney function.
With antibiotics with a pronounced nephrotoxic effect (gentamicin): increased risk of developing lactic acidosis.
With corticosteroids (systemic and for topical use), beta2-agonists and diuretics with intrinsic hyperglycemic activity: the patient should be informed of the need for more frequent monitoring of morning blood glucose levels, especially at the beginning of combination therapy. It may be necessary to adjust the doses of hypoglycemic therapy during the use or after the abolition of the above drugs.
With ACE inhibitors: ACE inhibitors can reduce the concentration of glucose in the blood. Doses of hypoglycemic therapy may need to be adjusted during use or after discontinuation of ACE inhibitors.
When a patient taking glimepiride is simultaneously prescribed or canceled other drugs, adverse reactions are possible: an increase or decrease in the hypoglycemic effect of glimepiride. Based on clinical experience with glimepiride and other sulfonylureas, the following drug interactions should be considered.
With drugs that are inducers and inhibitors of the CYP 2 C 9 isoenzyme: glimepiride is metabolized with the participation of the CYP 2 C 9 isoenzyme. Its metabolism is affected by the simultaneous use of inducers of the CYP 2 C 9 isoenzyme, for example, rifampicin (the risk of reducing the hypoglycemic effect of glimepiride when used simultaneously with inducers of the CYP 2 C 9 isoenzyme and an increase in the risk of hypoglycemia in case of their withdrawal without dose adjustment of glimepiride) and inhibitors of the isoenzyme CYP 2 C 9, for example, fluconazole (increased risk of developing hypoglycemia and side effects of glimepiride when taken simultaneously with inhibitors of the isoenzyme CYP 2 C 9 and the risk of reducing its hypoglycemic effect when they are canceled without dose adjustment glimepiride).
With drugs that enhance the hypoglycemic effect of glimepiride: insulin and oral hypoglycemic drugs, ACE inhibitors, anabolic steroids, male sex hormones, chloramphenicol, indirect anticoagulants, coumarin derivatives, cyclophosphamide, disopyramide, fenfluramine, pheniramidol, fibrates, fluoxetine, guanethidine, ifosfamide, MAO inhibitors, miconazole, fluconazole, aminosalicylic acid, pentoxifylline (high parenteral doses), phenylbutazone, azapropazone, oxyphenbutazone, probenecid, quinolone antimicrobials, salicylates, sulfinpyrazone, clarithromycin, sulfanilamide antimicrobials, tetracyclines, tritoqualin, trofosfamide: an increased risk of hypoglycemia when these drugs are co-administered with glimepiride and a risk of worsening glycemic control when they are discontinued without dose adjustment of glimepiride.
With drugs that weaken the hypoglycemic effect: acetazolamide, barbiturates, corticosteroids, diazoxide, diuretics, epinephrine (adrenaline) or other sympathomimetics, glucagon, laxatives (long-term use), nicotinic acid (high doses), estrogens, progestogens, phenothiazines, phenytoin, rifampicin , thyroid hormones: the risk of worsening glycemic control when used together with these drugs and an increased risk of hypoglycemia if they are discontinued without dose adjustment of glimepiride.
With blockers of histamine H2 receptors, beta-blockers, clonidine, reserpine, guanethidine: both an increase and a decrease in the hypoglycemic effect of glimepiride are possible. Careful monitoring of blood glucose levels is necessary. Beta-blockers, clonidine, guanethidine and reserpine, as a result of blocking the reactions of the sympathetic nervous system in response to hypoglycemia, can make the development of hypoglycemia more invisible to the patient and the doctor and thereby increase the risk of its occurrence.
With ethanol: acute and chronic use of ethanol can unpredictably either weaken or increase the hypoglycemic effect of glimepiride. In acute alcohol intoxication, the risk of developing lactic acidosis increases, especially in case of skipping or insufficient food intake, the presence of liver failure. Alcohol (ethanol) and preparations containing ethanol should be avoided.
With indirect anticoagulants, coumarin derivatives: Glimepiride can both enhance and reduce the effects of indirect anticoagulants, coumarin derivatives.
With bile acid sequestrants: colesevelam binds to glimepiride and reduces the absorption of glimepiride from the gastrointestinal tract. In the case of the use of glimepiride, at least 4 hours before ingestion of colesevelam, no interaction is observed. Therefore, glimepiride must be taken at least 4 hours before taking colesevelam.
Side effect
Taking a combination of metformin hydrochloride and glimepiride, either as a free combination of separate drugs of metformin hydrochloride and glimepiride, or as a fixed-dose combination of metformin hydrochloride and glimepiride, is associated with the same safety characteristics as the use of each of these drugs. separately.
metformin hydrochloride
On the part of metabolism: lactic acidosis.
From the digestive system: nausea, vomiting, diarrhea, abdominal pain, increased gas formation, flatulence and anorexia. These symptoms are mostly transient and resolve spontaneously with continued treatment. In some cases, it may be useful to temporarily reduce the dose.
At the beginning of metformin hydrochloride treatment, about 3% of patients may experience an unpleasant or metallic taste in the mouth, which usually disappears spontaneously.
On the part of the liver and biliary tract: abnormal liver function tests or hepatitis, which regressed when metformin hydrochloride was discontinued. With the development of the above or other undesirable reactions, the patient should immediately inform his doctor about this. Since some adverse reactions, incl. hypoglycemia, lactic acidosis, hematological disorders, severe allergic and pseudo-allergic reactions and liver failure can threaten the patient's life, in the event of such reactions, the patient should immediately inform his doctor and stop further taking the drug until instructions from the doctor.
From the skin and subcutaneous tissues: erythema, itching, rash.
From the hemopoietic system: anemia, leukocytopenia or thrombocytopenia. Patients on long-term use of metformin hydrochloride experience a, usually asymptomatic, decrease in vitamin B12 concentrations in