Jardins - instructions for use, analogs, testimonials and release forms (tablets 10 mg and 25 mg) of the drug for the treatment of non-insulin-dependent diabetes mellitus type 2 in adults, children and pregnancy. Composition

In this article, you can read the instructions for using the drug Jardins. There are reviews of visitors to the site - consumers of this medication, as well as opinions of doctors of specialists on the use of Jardins 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 Jardins 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.

Jardins - oral hypoglycemic drug. Empaglyflosin (an active ingredient in the Jardins preparation) is a reversible, highly active, selective and competitive inhibitor of the sodium-dependent type 2 glucose transporter with the concentration necessary to inhibit 50% of the enzyme activity (IC50) equal to 1.3 nmol. The selectivity of Empagliflozin is 5000 times that of the 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.

Jardins 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 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 clinical trials it was found that in patients with type 2 diabetes mellitus the excretion of glucose by the kidneys increased immediately after the application of the first dose of Jardins; 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, making, on application of empaglyflosin, a dose of 25 mg once a day, on average, 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.

Jardins reduces the concentration of glucose in the blood plasma, both in the case of an empty stomach and after a meal.

The mechanism of action of Jardins does not depend on 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, including the HOMA-beta index (homeostasis assessment model) and the ratio of proinsulin to insulin.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.

In clinical studies, where Jardins was used in the form of monotherapy; combined therapy with metformin; combined therapy with Metformin in patients with newly diagnosed type 2 diabetes mellitus; combined therapy with metformin and sulfonylurea derivatives; combination therapy with pioglitazone +/- metformin; combined therapy with linagliptin in patients with newly diagnosed type 2 diabetes mellitus; combined therapy with linagliptin, added to the therapy with metformin; combined therapy with metformin in comparison with Glimepiride (data from a 2-year study); combined therapy with insulin (regimen of multiple injections of insulin) +/- metformin; combined therapy with basal insulin; combined therapy with dipeptidyl peptidase-4 inhibitor (DPP-4),metformin +/- another hypoglycemic oral drug, a statistically significant decrease in glycosylated hemoglobin (HbA1c), a decrease in fasting plasma glucose, and a reduction in blood pressure and body weight have been demonstrated.

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 main way of metabolism of empaglyflozin in humans is glucuronization with the participation of uridine-5-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8 and UGT1A9. The most frequently detected metabolites of empaglyflozin are three glucuronic conjugates (2-O, 3-O and 6-O glucuronide). The systemic effect of each metabolite is small (less than 10% of the total effect of empaglyflosin). 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, 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

Diabetes mellitus type 2 (insulin-independent or diabetes insipidus):

• as monotherapy in patients with inadequate glycemic control only against the background of diet and exercise, the appointment of metformin which is considered impractical in view of intolerance (including to reduce excess weight or weight loss);
• 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.

Forms of release

Tablets coated with 10 mg and 25 mg.

Instructions for use and dosage

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

The recommended initial dose is 10 mg once a day. If the daily dose of 10 mg does not provide adequate glycemic control, the dose can be increased to 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 one day.

Patients with renal insufficiency with a glomerular filtration rate of less than 45 ml / min / 1.73 m2 should not be used.

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

Side effect

The overall incidence of adverse events in patients receiving empaglyflosin or placebo in clinical trials was similar. The most common adverse reaction was hypoglycemia, observed with the use of empaglyflosin in combination with sulfonylureas or insulin derivatives:

• vaginal candidiasis;
• vulvovaginitis;
• balanitis and other genital infections;
• urinary tract infections;
• hypoglycemia (when combined with sulfonylureas or insulin derivatives);
• hypovolemia;
• frequent urination;
• dysuria;
• itching.

Description of individual adverse reactions

Hypoglycaemia

The frequency of hypoglycemia depended on the associated concomitant hypoglycemic therapy and was similar in patients taking empaglyflosin or placebo as a monotherapy,as well as in the case of the addition of empaglyflozin to metformin and in the case of the addition of empaglyflozin to pioglitazone (+/- metformin). In the case of the use of empaglyflosin in combination with metformin and sulfonylurea derivatives, and in the case of using empaglyflosin in combination with insulin (+/- metformin and +/- sulfonylurea derivative), the incidence of hypoglycemia was higher than with placebo in the same combination.

Severe hypoglycemia (a condition requiring medical intervention). The incidence of severe hypoglycemia was low (less than 1%) and similar in patients taking empaglyflosin and placebo as monotherapy, and also when empaglyflosin was added to metformin and when empaglyflosin was added to pioglitazone (+/- metformin). In the case of the use of empaglyflosin in combination with metformin and sulfonylureas, in combination with insulin (+/- metformin and +/- sulfonylureas), the incidence of hypoglycemia was higher than with placebo in the same combination.

Increased urination

The frequency of frequent urination (assessed symptoms such as pollakiuria, polyuria, nocturia) was higher in the case of empaglyflosin (at a dose of 10 mg: 3.5%, 25 mg: 3.3%) than with placebo (1.4%).The frequency of development of nocturia was comparable in the group of patients taking Jardins, and in the group of patients taking placebo (less than 1%). The intensity of these side effects was mild or moderate.

Urinary tract infections

The incidence of urinary tract infections was similar in the case of 25 mg Jardins and placebo (7.0% and 7.2%, respectively), but higher with empagliflozin 10 mg (8.8%). As with placebo, urinary tract infections with empaglyflosin were more common in patients with chronic and recurrent urinary tract infections in history. The intensity of urinary tract infections was similar in patients taking empaglyflosin and placebo. Urinary tract infections were more frequent in women.

Genital infections

The incidence of adverse events such as vaginal candidiasis, vulvovaginitis, balanitis and other genital infections was higher in the case of Jardins (10 mg: 4.0%, 25 mg: 3.9%) than with placebo (1.0%) . Genital infections were more frequent in women. The intensity of genital infections was mild or moderate.

Hypovolemia

The incidence of hypovolemia (expressed as a decrease in blood pressure, orthostatic arterial hypotension, dehydration, syncope) was similar in the case of empaglyflosin (10 mg: 0.6%, 25 mg: 0.4%) and placebo (0.3%). In patients over the age of 75 years, the incidence of hypovolemia was comparable in patients taking empaglyflosin at a dose of 10 mg (2.3%) and placebo (2.1%), but higher in patients taking empagliflozin at a dose of 25 mg (4.3%).

Contraindications

• type 1 diabetes mellitus;
• diabetic ketoacidosis;
• rare hereditary disorders (lactase deficiency, lactose intolerance, glucose-galactose malabsorption);
• renal failure with a persistent glomerular filtration rate of less than 45 ml / min / 1.73 m2;
• application in combination with analogues of glucagon-like peptide-1 (due to the lack of data on efficacy and safety);
• pregnancy;
• lactation period (breastfeeding);
• age over 85 years;
• children and adolescents under 18 years of age (due to insufficient data on effectiveness and safety);
• hypersensitivity to any component of the drug.

Application in pregnancy and lactation

The use of Jardins during pregnancy is contraindicated because of insufficient 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, breast-feeding 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 Jardins, undesirable reactions caused by hypovolemia were more frequent (compared with patients receiving placebo).

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

special instructions

The drug Jardins is not recommended for patients with type 1 diabetes and for the treatment of 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 (250 mg / dL)).

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. The use of the Jardins drug should be stopped 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, patients with severe dehydration,patients with a history of ketoacidosis or patients who have a low secretory activity of the pancreatic beta cells. In such patients, the Jardins drug should be used with caution. Care must be taken when lowering the dose of insulin.

The drug Jardins contains 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 the Jardins drug is combined with sulfonylurea derivatives or with insulin, a dose reduction of the sulfonylurea / insulin derivatives may be required because of the risk of developing hypoglycemia.

Empaglyflosin has not been studied in combination with glucagon-like peptide-1 analogues (GLP-1).

The effectiveness of the drug Jardins depends on the function of the kidneys, therefore it is recommended to monitor the kidney function before its appointment and periodically during treatment (at least once a year),as well as before the appointment of concomitant therapy, which can adversely affect the function of the kidneys. It is not recommended to use the drug in patients with renal insufficiency (GFR less than 45 ml / min).

Patients aged 75 years and older have an increased risk of dehydration, so Jardins should be given with caution to patients in this category. 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 older than 85 years is limited, and therefore it is not recommended to prescribe the drug Jardins to patients of this age group.

According to the mechanism of action, the use of the drug Jardins can lead to a moderate decrease in blood pressure. 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 Jardins develops conditions that can lead to loss of fluid (for example, in diseases of the digestive 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.

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 (such as pyelonephritis and urosepsis) have been observed with similar 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.

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

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 with the management of vehicles and mechanisms, because When using Jardins (especially in combination with sulfonylureas and / or insulin derivatives) hypoglycemia may develop.

Drug Interactions

Pharmacodynamic interaction

Jardins 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 of empaglyflosin and drugs, which are substrates of the isoenzymes CYP450 and UGT1A1, 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 the data obtained in the studies, it is believed that the ability of empaglyflosin 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.

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 the Jardins drug 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, torasemide and hydrochlorothiazide. With the simultaneous use of empaglyflozin with gemfibrozil, rifampicin and probenecid, an increase in the AUC value of empaglyflosin was observed at 59%, 35% and 53%, respectively, but these changes were not considered clinically significant.

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 Jardins

Jardins does not have structural analogs for the active substance.

Analogues on the curative effect (agents for the treatment of non-insulin-dependent diabetes mellitus):

• Amaryl;
• Anistat;
• Arfazetine;
• B Insulin S.T. Berlin-Chemie;
• Bagomet;
• Berselsulin;
• Biosulin P;
• Vipidia;
• Galvus;
• Galvus Met;
• Gensulin;
• Glemaz;
• Glybamide;
• Glybenez;
• Glibenclamide;
• Glybometh;
• Glimepiride;
• Gliiformin;
• Glucophage;
• Glucophage Long;
• Depo insulin C;
• Diabeton;
• Diabrazide;
• Dibikor;
• Insulin C;
• Xenical;
• Levemir;
• Listat;
• Maninil;
• Metogamma;
• Metformin;
• Mixtard;
• Monotard;
• NovoMiks;
• Novonorm;
• NovoRapid;
• Novoformin;
• Pensulin;
• Protafan;
• Raizodeg FlexTach;
• Reduxin Met;
• Reclild;
• Rinsulin;
• Saxenda;
• Silubin retard;
• Siofor;
• Starlix;
• Trakor;
• Ultradard;
• Formethine;
• Formina Pliva;
• Chitozan Evalar;
• Humalog;
• Humulin;
• Cigapan;
• Erbisol;
• Euglucon;
• Januvia.

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