Expiration date: 01/2025

Pharmacological action 

Gardens - retrieveimage inhibitor of glucose Transporter type 2

Testimony

Diabetes type 2:

• as monotherapy in patients with inadequate glycemic control only in the context of diet and exercise, the appointment of which Metformin is not considered appropriate in view of the intolerance;
  
• as combination therapy with other hypoglycemic agents, including insulin, when used therapy in conjunction with diet and exercise does not provide the necessary glycemic control.
  

Contraindications

• hypersensitivity to any component of the drug;
  
• diabetes mellitus type 1;
  
• diabetic ketoacidosis;
  
• rare inherited disorders (deficiency of lactase, lactose intolerance, glucose-galactose malabsorption);
  
• renal failure with GFR < 45 ml/ min per 1.73 m2 (due to inefficiency);
  
• pregnancy and breastfeeding;
  
• age older than 85 years;
  
• use in combination with glucagonomas analogs of peptide 1 (in the absence of data on efficacy and safety);
  
• children up to age 18 years (due to the lack of data on efficacy and safety).
  

With caution

• patients with risk of development of hypovolemia (the use of antihypertensive drugs with cases of arterial hypotension in history);
  
• diseases of the digestive tract, leading to loss of fluid;
  
• age older than 75 years;
  
• use in combination with sulfonylureas or insulin;
  
• infections of the genitourinary system.
  

Application of pregnancy and breastfeeding

Application Empagliflozin during pregnancy is contraindicated due to insufficient data on efficacy and safety.

Data obtained in preclinical studies in animals, indicate the penetration of embilipitiya in breast milk. Does not exclude the risk of exposure on infants and children while breastfeeding. Application Empagliflozin in the period of breast-feeding is contraindicated. If necessary, use Empagliflozin in the period of breast-feeding, breast-feeding should be discontinued.

Special instructions

Drug Gardens not recommended for patients with diabetes type 1 diabetes and for the treatment of diabetic ketoacidosis.

The maximum daily dose of the drug Gardens contains 113 mg of lactose, so the drug should not be administered to patients with rare hereditary disorders like lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Clinical studies have shown that treatment ampilifier does not increase cardiovascular risk. Application Empagliflozin in the dose of 25 mg did not result in prolongation of the QT interval.

In a joint application of the drug Gardens with sulfonylureas or insulin may require lower doses of sulfonylureas/ insulin because of the risk of hypoglycemia.

Studied the combination of hypoglycemic drugs

Empagliflozin not been studied in combination with analogues glucagonoma peptide 1 (GLP-1).

Monitoring of renal function

The effectiveness of the drug Jardins depends on renal function. It is therefore recommended to monitor renal function prior to his appointment, and periodically during treatment (at least once a year) and also before assigning to concomitant medication that may affect kidney function. Patients with renal insufficiency (GFR less than 45 ml/min), the drug is not recommended.

Elderly patients

In patients aged 75 years and over have an increased risk of dehydration. In these patients receiving Empagliflozin, more often (in comparison with patients on placebo) were observed adverse reactions caused by the hypovolemia. Experience in the use of embilipitiya in patients older than 85 years is limited, therefore, to assign the drug to Jardins patients older than 85 years is not recommended.

Use in patients with risk of development of hypovolemia

According to the mechanism of action of the drug Gardens can lead to moderate decrease in blood pressure. Therefore, the drug should be used with caution in cases where the decrease of arterial pressure is undesirable for example, patients with cardiovascular disease; patients receiving antihypertensive drugs (cases of arterial hypotension in history), and in patients older than 75 years.

If the patient taking the drug Jardins develop the condition, which can lead to loss of fluids (e.g., diseases of the gastrointestinal tract), should carefully monitor the patient's condition, blood pressure, and monitor hematocrit and electrolyte balance. May need to be temporarily, until the restoration of water balance, is discontinued.

Urinary tract infection

The incidence of these side effects, as urinary tract infections, were comparable when using Empagliflozin in the dose of 25 mg and placebo, and higher when using Empagliflozin at a dose of 10 mg. of Complicated urinary tract infection (such as pyelonephritis and urosepsis) was observed with similar frequency in patients taking Empagliflozin and placebo. In the case of complicated urinary tract infections required temporary cessation of therapy ampilifier.

Laboratory analysis of urine

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

Effects on ability to drive vehicles and mechanisms

Clinical studies on the effect of anaglyptini on the ability to drive vehicles and mechanisms was conducted. Patients should observe caution while driving vehicles and mechanisms, since the use of the drug Gardens (especially in combination with sulfonylureas and/or insulin) may develop hypoglycemia.

Composition

1 tablet contains:

Active substance: Empagliflozin 10 or 25 mg;

Excipients: lactose monohydrate, cellulose microcrystalline, hyprolose (hydroxypropyl cellulose), croscarmellose sodium, silica colloidal anhydrous, magnesium stearate.

The composition of the film shell: Opadry yellow (02B38190) (hypromellose 2910, titanium dioxide (E171), talc, macrogol 400, dye iron oxide yellow (E172)).

Method of application and doses

Monotherapy or combination therapy

The recommended starting dose is 10 mg (1 tablet of 10 mg) 1 times a day, orally.

In the case that a daily dose of 10 mg does not provide adequate glycemic control, the dose may be increased to 25 mg (1 tablet with a dosage of 25 mg 1 time per day). The maximum daily dose is 25 mg.

Drug Gardens may be taken with or without food at any time of the day.

Actions when skipping one or more doses of a medicinal product

The release dose, the patient should take the drug as soon as he remembers. You should not take a double dose in one day.

Special groups of patients

When kidney failure with GFR 45 to 90 ml/min/1.73 m2 dose adjustment is not required.

Patients with renal insufficiency with a GFR less than 45 ml/min/1.73 m2 to use the drug not recommended due to inefficiency.

Patients with impaired hepatic function dose adjustment is not required.

Side effects

The overall incidence of adverse events in patients receiving Empagliflozin or placebo in clinical trials were similar. The most common adverse reaction was hypoglycaemia observed when using Empagliflozin in combination with sulfonylureas or insulin (see description of selected adverse reactions).

Adverse reactions observed in patients receiving Empagliflozin  in placebo-controlled studies presented in the Table below (adverse reactions were classified according to the organs and systems and in accordance with predpochitaemaya in MedDRA?????????), indicating their absolute frequency. Category frequencies are defined as follows: very common (?1/10), common (?1/100 to

Table. Side effects, observed in placebo-controlled studies

Classification according to the bodies systems	Very often	Often
Infectious and parasitic diseases			Vaginal candidiasis, vulvovaginitis, balanitis and other genital infection Urinary tract infection
Violations of metabolism and nutrition	Hypoglycaemia (when used together with sulfonylureas or insulin)	Hypovolemia
Violations of the kidneys and urinary tract		Frequent urination

Description of selected adverse reactions

Hypoglycemia

The frequency of hypoglycaemia depended on the applied concomitant hypoglycemic therapy.

Mild hypoglycemia (blood glucose of 3.0 - 3.8 mmol/l (54-70 mg/DL))

The incidence of mild hypoglycemia was similar in patients taking Empagliflozin or placebo as monotherapy and when you add Empagliflozin to Metformin and if you add Empagliflozin to pioglitazone (± Metformin). In the case of the appointment of embilipitiya in combination with Metformin and sulfonylureas the incidence of hypoglycemia was higher (10 mg: 10,3%; 25 mg: 7.4 percent) than in the appointment of a placebo in the same combination (5,3%).

Severe hypoglycemia (blood glucose below 3 mmol/l (54 mg/DL))

The incidence of severe hypoglycemia was similar in patients taking Empagliflozin and placebo as monotherapy. In the case of the appointment of embilipitiya in combination with Metformin and sulfonylureas the incidence of hypoglycemia was higher (10 mg: 5,8 %; 25 mg: 4.1 per cent) than in the appointment of a placebo in the same combination (3,1%).

High .urination

The frequency of frequent urination (estimated symptoms such as pollakiuria, polyuria, nocturia) was higher in the case of anaglyptini (at a dose of 10 mg: 3.4%, and at a dose of 25 mg: 3.2 per cent) than in placebo (1%). The incidence of nocturia was comparable in patients who took Empagliflozin and in the group of patients taking placebo (less than 1%). The intensity of these side effects was weak or moderate.

Urinary tract infection

The incidence of urinary tract infections was similar in the case of embilipitiya 25 mg and placebo (7.6 percent) , but higher in the case of embilipitiya 10 mg (9.3 per cent). Also as in the case of the use of placebo, urinary tract infection on a background of reception of embilipitiya were more often noted in patients with chronic and recurrent infections of the urinary tract in anamnesis. Intensity of urinary tract infections was similar in patients receiving Empagliflozin and placebo. Urinary tract infections were reported more often in women.

Genital infections

The incidence of such adverse effects as vaginal candidiasis. vulvovaginitis, balanitis and other genital infections were higher in the case of anaglyptini (at a dose of 10 mg: 4.1% in the dose of 25 mg: 3.7%) than when using a placebo (0,9%). Genital infections were reported more often in women. The intensity of genital infections were mild or moderate.

Hypovolemia

The incidence of hypovolemia (that was expressed in decrease in blood pressure, orthostatic hypotension, dehydration, syncope) was similar in the case of anaglyptini (at a dose of 10 mg of 0.5%. in the dose of 25 mg: 0.3%) and placebo (0.3 percent). In patients older than 75 years, the incidence of hypovolemia were similar in patients taking Empagliflozin at a dose of 10 mg (2.3%) and placebo (2.1 percent), but higher in the patients taking Empagliflozin in the dose of 25 mg (4.4 per cent).

Drug interactions

Assessment of drug interactions in vitro

Empagliflozin not inhibits, inactivates no and it does not induce CYP450 isoenzymes. The main metabolic Empagliflozin in humans is glucuronidation, with the participation of uridine-5'-diphospho-glucuronosyltransferases UGT2B7, UGT1A3, UGT1A8, and UGT1A9. Empagliflozin not inhibit UGT1A1. Drug interactions Empagliflozin and drugs that are substrates of CYP450 isoenzymes and UGT1A1 are considered unlikely.

Empagliflozin is a substrate for the glycoprotein P (P-gp) and protein that determines the resistance of breast cancer (BCRP), but in therapeutic doses does not inhibit these proteins. On the basis of data obtained in studies in vitro, it is believed that the ability of anaglyptini to interact with drugs that are substrates for P glycoprotein (P-gp). unlikely. Empagliflozin is a substrate for organic anion transporters: OAT3, OATP1B1 and OATP1B3, but is not a substrate for organic anion transporters 1 (OAT1) and organic cation transporters 2 (OCT2). However, drug interactions Empagliflozin with drugs that are substrates for the proteins described above, vectors are considered to be unlikely.

Assessment of drug interactions in vivo

Pharmacokinetics Empagliflozin does not change in healthy volunteers in the case of joint use with Metformin. the glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, hydrochlorothiazide and torasemid. In a joint application, Empagliflozin with gemfibrozil, rifampicin and probenecid showed a higher AUC values, Empagliflozin 59%, 35% and 53%, respectively, but these changes were not considered clinically significant.

Empagliflozin has no clinically meaningful effect on the pharmacokinetics of Metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, digoxin, ramipril, simvastatin, hydrochlorothiazide, torasemid and oral contraceptive pills.

Diuretics

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

Insulin and drugs that increase its secretion

Insulin and drugs that increase its secretion, such as sulfonylureas, may increase the risk of hypoglycemia. Therefore, while the use of Empagliflozin with insulin and drugs that increase its secretion, you might need to reduce their doses, to avoid the risk of hypoglycemia.

Overdose

Symptoms

During controlled clinical studies a single dose of anaglyptini, reaching 800 mg (32% exceeding the maximum daily dose) in healthy volunteers and multiple doses, up to 100 mg (4 times higher than the maximum daily dose) in patients with type 2 diabetes was well tolerated. The observed increase in urine volume was not dependent on the dose and had no clinical significance. Experience in the use of doses greater than 800 mg, no.

Treatment

In case of overdose, it is advisable to remove any unabsorbed drug from the gastrointestinal tract, implementation of clinical monitoring and symptomatic treatment.

Storage conditions

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

Shelf life

3 years