Empagliflozin - instructions for use, analogs, reviews and release forms (10 mg and 25 mg tablets) drugs for the treatment of non-insulin dependent diabetes mellitus in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Empaglyflozin. Presented are reviews of visitors to the site - consumers of this medication, as well as opinions of physicians specialists on the use of empaglyflosin in their practice. A big request is to actively add their feedback on the drug: the medicine helped or did not help get rid of the disease, which were observed complications and side effects, possibly not declared by the manufacturer in the annotation. Analogues of Empaglyflozin in the presence of existing structural analogues. Use for the treatment of non-insulin-dependent diabetes mellitus type 2 in adults, children, as well as during pregnancy and lactation. Composition of the preparation.

Empaglyflozin - reversible, highly active, selective and competitive inhibitor of sodium-dependent glucose transporter type 2. The selectivity of Empagliflozin is 5000 times that of a sodium-dependent glucose transporter of type 1, responsible for the absorption of glucose in the intestine. In addition, it has been found that empaglyflosin has a high selectivity for other glucose carriers responsible for the homeostasis of glucose in various tissues.

The sodium-dependent type 2 glucose transporter is the primary carrier protein responsible for the reabsorption of glucose from the renal glomeruli back into the bloodstream. Empaglyflosin improves glycemic control in patients with type 2 diabetes by reducing the reabsorption of glucose in the kidneys. The amount of glucose released by the kidney with this mechanism depends on the concentration of glucose in the blood and the glomerular filtration rate (GFR). Inhibition of the sodium-dependent type 2 glucose transporter in patients with type 2 diabetes mellitus and hyperglycaemia results in excretion of excess glucose by the kidneys.

In the course of clinical studies,that in patients with type 2 diabetes mellitus the excretion of glucose by the kidneys increased immediately after the first dose of empaglyflosin; this effect lasted for 24 hours. The increase in the excretion of glucose by the kidneys persisted until the end of the 4-week treatment period, when administered with empaglyflosin at a dose of 25 mg once a day, an average of about 78 grams per day. In patients with type 2 diabetes mellitus, an increase in the excretion of glucose by the kidneys led to an immediate decrease in the concentration of glucose in the blood plasma.

Empagliflozin (in a dose of 10 mg and 25 mg) reduces the concentration of glucose in the blood plasma, both in the case of fasting and after eating.

The mechanism of action of empagliflozin is independent of the functional state of the beta cells of the pancreas and the metabolism of insulin. Positive effects of empaglyflosin on surrogate markers of beta-cell functional activity were noted. In addition, the additional excretion of glucose by the kidneys causes a loss of calories, which is accompanied by a reduction in the volume of adipose tissue and a decrease in body weight.

Glucosuria, observed during the application of empaglyflosin, is accompanied by a slight increase in diuresis, which can contribute to a moderate decrease in blood pressure (BP).

In clinical studies using empagliflozin in the form of monotherapy and combination therapy, a statistically significant decrease in glycosylated hemoglobin (HbA1c), a decrease in fasting plasma glucose concentration, and a decrease in blood pressure and body weight were demonstrated.

A clinical study examined the effect of the drug on the incidence of cardiovascular events in patients with type 2 diabetes and high cardiovascular risk receiving standard therapy, which included hypoglycemic drugs and drugs for the treatment of cardiovascular diseases. As a primary endpoint, cases of cardiovascular death, myocardial infarction without a fatal outcome and a stroke without a fatal outcome were evaluated. Additional predefined endpoints were cardiovascular death, total mortality, development of nephropathy or progressive deterioration of nephropathy, hospitalization for heart failure.

Empagliflozin improved overall survival by reducing the incidence of cardiovascular death, reduced the risk of hospitalization for heart failure, and reduced the risk of nephropathy or a progressive deterioration of nephropathy.

In patients with initial macroalbuminuria, it was found that Empagliflozin significantly more often compared with placebo led to stable normo- or microalbuminuria.

Composition

Empagliflozin + auxiliary substances.

Pharmacokinetics

The pharmacokinetics of empaglyflosin has been extensively studied in healthy volunteers and in patients with type 2 diabetes mellitus. After ingestion, empaglyflosin is rapidly absorbed. Eating does not have a clinically significant effect on the pharmacokinetics of empaglyflosin. The pharmacokinetics of empaglyflosin in healthy volunteers and in patients with type 2 diabetes mellitus was generally similar. After ingestion of labeled empagliflozin in healthy volunteers, approximately 96% of the dose was excreted (through the intestine - 41%, kidneys - 54%). Through the intestine, most of the labeled drug was excreted unchanged. Only half of the labeled preparation was excreted in the unchanged form. The body mass index (BMI), sex, race and age did not have a clinically significant effect on the pharmacokinetics of empaglyflosin. Studies of the pharmacokinetics of Empaglyflosin in children have not been conducted.

Indications

• non-insulin-dependent diabetes mellitus (type 2 diabetes) - as monotherapy in patients with inadequate glycemic control only against a background of diet and exercise, the appointment of metformin to which is impossible due to intolerance;
• Type 2 diabetes mellitus (non-insulin-dependent) - as part of combination therapy with other hypoglycemic agents, including insulin, when the therapy used together with diet and exercise does not provide the necessary glycemic control;
• Type 2 diabetes mellitus with a high cardiovascular risk in combination with standard therapy for cardiovascular disease. The goal is to reduce overall mortality by reducing cardiovascular mortality, as well as reducing cardiovascular mortality or hospitalization for heart failure. High cardiovascular risk is defined as the presence of at least one of the following diseases and / or conditions: ischemic heart disease (IHD), namely myocardial infarction in anamnesis, coronary artery bypass grafting, coronary artery disease with one coronary artery disease,IHD with lesion of several coronary vessels; ischemic or hemorrhagic stroke in history; diseases of peripheral arteries (with or without symptoms).

Forms of release

Tablets coated with 10 mg and 25 mg.

Instructions for use and dosing regimen

The drug empaglyflosin is taken orally, at any time of the day, regardless of food intake.

The recommended initial dose is 10 mg (1 tablet at a dosage of 10 mg) once a day. If the daily dose of 10 mg does not provide adequate glycemic control, the dose may be increased to 25 mg (1 tablet at a dosage of 25 mg) once a day. The maximum daily dose is 25 mg.

If a dose is missed, the patient should take the drug as soon as he remembers it. Do not take a double dose in 1 day.

Patients with renal insufficiency with GFR less than 45 ml per minute for 1.73 m2 to apply the drug is not recommended; with GFR greater than 45 mL per minute at 1.73 m2 dose adjustment is not required.

Patients with violations of the function of the liver dose adjustment is not required.

Side effect

• vaginal candidiasis;
• vulvovaginitis (inflammation of the mucous membranes of the vulva and vagina);
• balanitis (inflammation of the skin of the glans penis);
• other genital infections;
• urinary tract infections;
• hypoglycemia (when combined with sulfonylureas or insulin derivatives);
• itching;
• hypovolemia (decrease in the volume of circulating blood);
• frequent urination;
• dysuria (violation of the process of urination).

Contraindications

• hypersensitivity to any component of the drug;
• type 1 diabetes mellitus;
• diabetic ketoacidosis (high concentration of glucose and ketone bodies in the blood due to insulin deficiency);
• renal failure with GFR less than 45 ml per minute at 1.73 m2;
• use in combination with analogues of glucagon-like peptide 1 (GLP-1) due to the lack of data on efficacy and safety;
• rare hereditary disorders (lactase deficiency, lactose intolerance, glucose-galactose malabsorption);
• pregnancy;
• lactation period (breastfeeding);
• age over 85 years;
• children and adolescents under 18 years (due to insufficient data on efficiency and safety).

Application in pregnancy and lactation

The use of empaglyflosin in pregnancy is contraindicated due to the lack of data on efficacy and safety.

The use of empaglyflosin during breastfeeding is contraindicated. The data obtained in preclinical studies in animals indicate the isolation of empaglyflosin with breast milk. The risk of exposure to newborns and children who are breastfed is not ruled out. If you need to use empaglyflozin during lactation, breastfeeding should be discontinued.

Use in children

Contraindicated use of the drug in children and adolescents under 18 years (due to lack of data on efficacy and safety).

Application in elderly patients

Patients aged 75 years and older have an increased risk of dehydration. In such patients receiving empaglyflosin, undesirable reactions caused by hypovolemia were more frequent (compared with patients receiving placebo).

Experience with the use of empaglyflosin in patients over 85 years of age is limited, therefore it is not recommended to prescribe the drug Empagliflozin to patients of this age group.

special instructions

The drug Empagliflozin is not recommended for patients with type 1 diabetes and for the treatment of diabetic ketoacidosis.

Diabetic ketoacidosis

With the use of inhibitors of the sodium-dependent glucose transporter of type 2, including empaglyflosin, there have been reports of rare cases of diabetic ketoacidosis. In some of these cases, the manifestations were atypical and were expressed in a moderate increase in the concentration of blood glucose (not more than 14 mmol / l).

The risk of developing diabetic ketoacidosis should be considered in the event of nonspecific symptoms such as nausea, vomiting, lack of appetite, abdominal pain, severe thirst, difficulty breathing, disorientation, unmotivated fatigue or drowsiness. If such symptoms develop, patients should be immediately examined for ketoacidosis regardless of blood glucose concentration. Use of the drug Empagliflozin should be discontinued or suspended until the diagnosis is established.

A higher risk of developing diabetic ketoacidosis is possible in patients on a diet with a very low carbohydrate content (in this case, this combination of drugs can stillmore increase ketone production in the body), patients with severe dehydration, patients with a history of ketoacidosis, or patients who have a low secretory activity of the beta cells of the pancreas. In such patients, Empaglyflosin should be used with caution. Care must be taken when lowering the dose of insulin.

In the preparation Empaglyflozin in a tablet with a dosage of 10 mg contains 162.5 mg of lactose, with a dosage of 25 mg - 113 mg of lactose, so the drug should not be used in patients with such rare hereditary disorders as lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Clinical studies have shown that treatment with empaglyflosin does not lead to an increase in cardiovascular risk. The use of empaglyflosin in a dose of 25 mg does not lead to an extension of the QT interval.

When a combination of Empaglyflosin with sulfonylurea derivatives or with insulin is used together, a reduction in the dose of sulfonylurea / insulin derivatives may be required because of the risk of developing hypoglycemia.

Empaglyflosin was not studied in combination with GLP-1 analogs.

Monitoring of kidney function

The effectiveness of the drug Empagliflozin depends on the function of the kidneys, therefore it is recommended to monitor the function of the kidneys before it is prescribed and periodically during treatment (at least once a year), and before prescribing concomitant therapy that can adversely affect kidney function. It is not recommended to use the drug in patients with renal insufficiency (GFR less than 45 ml per minute at 1.73 m2).

Use in patients at risk of developing hypovolemia

According to the mechanism of action, the use of the drug Empagliflozin can lead to a moderate decrease in blood pressure (BP). Therefore, use the drug with caution in those cases where a decrease in blood pressure is undesirable, for example, in patients with cardiovascular disease; patients taking antihypertensive drugs (with history of arterial hypotension), as well as in patients over the age of 75 years.

If the patient receiving the drug Empaglyflozin develops conditions that can lead to fluid loss (for example, in diseases of the gastrointestinal tract (GI tract)), careful monitoring of the patient's condition, blood pressure, and monitoring of hematocrit and electrolyte balance should be carried out.It may take a temporary, until the restoration of the water balance, discontinuation of the drug.

Urinary tract infections

The incidence of such side effects as urinary tract infections was comparable with empaglyflosin at a dose of 25 mg and placebo, and higher with empaglyflosin at a dose of 10 mg. Complicated urinary tract infections (including severe urinary tract infections such as pyelonephritis and urosepsis) have been observed at a comparable frequency in patients taking empaglyflosin and placebo. In the case of development of complicated infections of the urinary tract, temporary discontinuation of therapy with empaglyflosin is necessary.

Laboratory analysis of urine

According to the mechanism of action, in patients taking the drug Empagliflozin, glucose in urine is determined.

Impact on the ability to drive vehicles and manage mechanisms

Clinical studies on the effect of empaglyflosin on the ability to drive vehicles and mechanisms have not been conducted. Patients should be careful in managing vehicles and mechanisms,since with the use of the drug Empagliflozin (especially in combination with derivatives of sulfonylureas and / or insulin) hypoglycemia may develop.

Drug Interactions

Pharmacodynamic interaction

Empagliflozin can enhance the diuretic effect of thiazide and loop diuretics, which in turn can increase the risk of dehydration and arterial hypotension.

Insulin and drugs that increase its secretion, such as sulfonylureas, can increase the risk of hypoglycemia. Therefore, with the simultaneous use of empaglyflosin with insulin and drugs that enhance its secretion, it may be necessary to reduce their dose, in order to avoid the risk of developing hypoglycemia.

Pharmacokinetic interaction: evaluation of drug interaction in vitro

Empagliflozin does not inhibit, inactivate or induce the isoenzymes of CYP450. The main way of metabolism of empaglyflozin in humans is glucuronization with the participation of uridine-5-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8 and UGT1A9. Empaglyflosin does not inhibit UGT1A1, UGT1A3, UGT1A8, UGT1A9 or UGT2B7. The drug interaction between empaglyflosin and drugs that are substrates of CYP450 and UGT isoenzymes is considered unlikely.

Empaglyflosin is a substrate for P-glycoprotein and a protein that determines the resistance of breast cancer (BCRP), but does not inhibit these proteins at therapeutic doses. Based on data obtained in in vitro studies, it is believed that the ability of empaglyflozin to interact with drugs that are substrates for P-glycoprotein is unlikely. Empagliflozin is a substrate for organic anionic carriers: OAT3, OATP1B1 and OATP1B3, but it is not a substrate for organic anionic transporter 1 (OAT1) and organic cationic transporter 2 (OCT2). However, the drug interaction of empaglyflozin with preparations that are substrates for the above-described carrier proteins is considered unlikely.

Pharmacokinetic interaction: evaluation of drug interaction in vivo

With the simultaneous use of empaglyflosin with other commonly used drugs, no clinically significant pharmacokinetic interaction was observed. The results of pharmacokinetic studies indicate that there is no need to change the dose of Empagliflozin while simultaneously using it with frequently used medications.

The pharmacokinetics of empaglyflozin does not change in healthy volunteers when it is combined with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, and in patients with type 2 diabetes in the case of combined use with torasemide and hydrochlorothiazide.

Empagliflozin does not have a clinically significant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, digoxin, ramipril, simvastatin, hydrochlorothiazide, torasemide and oral contraceptives in healthy volunteers.

Analogues of the drug Empagliflozin

Structural analogs for the active substance:

• Jardins.

Analogues of the preparation Empagliflozin on the curative effect (means for the treatment of insulin-dependent diabetes mellitus):

• Avandamet;
• Avandia;
• Adebit;
• Amalvia;
• Amaryl;
• Antidiab;
• Arfazetine;
• Bagomet;
• Baeta;
• Berselsulin;
• Bethanase;
• Biosulin;
• Butamide;
• Vazoton;
• Victoria;
• Vipidia;
• Galvus;
• Gensulin;
• Glybenez;
• Glibenclamide;
• Glidiab;
• Glucovans;
• Glucophage;
• Gljurenorm;
• Guacarbene;
• Guarem;
• Dioniel;
• Diabeton;
• Diabrazide;
• Invokana;
• Insulin C;
• Levemir;
• Lysumia;
• Maniglid;
• Maninil;
• Metogamma;
• Metformin;
• Mixtard;
• Monotard;
• NovoMiks;
• Novonorm;
• Novoformin;
• Noliprel;
• OngliSa;
• Orsotene;
• Pankragen;
• Pensulin;
• Protafan;
• Raizodeg;
• Reduxin Met;
• Rinsulin;
• Silubin;
• Siofor;
• Telzap;
• Tresib;
• Tudzheo SoloStar;
• Ultradard;
• Formethine;
• Formin;
• Chloropropamide;
• Humalog;
• Humulin;
• Cigapan;
• Erbisol;
• Euglucon;
• Januvia.

Review of the endocrinologist

The incidence of diabetes increases from year to year, including the incidence of type 2 diabetes, insulin-dependent. Sometimes it is very difficult to choose adequate therapy. I prescribe the drug Empaglyflosin to type 2 diabetics who have a history of myocardial infarction, stroke, or who have undergone coronary artery bypass surgery. Patients note that it is convenient to be treated with this drug, since it should be taken once a day. Patients usually tolerate Empagliflozin therapy well. In my practice there was only one case when the patient during the treatment began to disturb the skin itch. This drug she had to cancel and pick up another one.

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