Jardiance tabs 10mg #30

Jardiance instruction

You can buy Jardiance here

Composition

1 tablet film coated contains:
Active substance:
empagliflozin - 10 mg / 25 mg;
Excipients:
lactose monohydrate - 162.50 / 113.0 mg, microcrystalline cellulose - 62.50 / 50.0 mg, hyprolose (hydroxypropylcellulose) - 7.5 / 6.0 mg, croscarmellose sodium - 5.0 / 4.0 mg, colloidal silicon dioxide - 1.25 / 1.0 mg, magnesium stearate - 1.25 / 1.0 mg;
Shell:
Opadry yellow (02В38190) - 7.0 / 6.0 mg (hypromellose 2910 - 3.5 / 3.0 mg, titanium dioxide (E 171) - 1.733 / 1.455 mg, talc - 1.4 / 1.2 mg, macrogol 400 - 0.35 / 0.3 mg, iron dye yellow oxide (E 172) - 0.018 / 0.015 mg).

Description

Tablets dosage of 10 mg
Round biconvex tablets with beveled edges, film-coated in light yellow color with the engraving of the company symbol on one side of the tablet and “S10” on the other side.
Tablets dosage 25 mg
Oval biconvex tablets with beveled edges, film-coated in light yellow color, with an engraving of the company's symbol on one side of the tablet and “S25” on the other side.
Pharmacotherapeutic group
Hypoglycemic agent for oral administration - inhibitor sodium type 2 glucose transporter
ATH code: А10ВХ12

Pharmacodynamics of Jardiance

Empagliflozin is a reversible, highly active, selective and competitive inhibitor of sodium-dependent glucose transporter type 2 with a concentration required to inhibit 50% of the enzyme activity (IC50) of 1.3 nmol. The selectivity of empagliflozin is 5,000 times higher than the selectivity of the sodium type 1 glucose transporter responsible for the absorption of glucose in the intestine. In addition, it was found that empagliflozin has a high selectivity for other glucose transporters responsible for glucose homeostasis in various tissues.
The sodium type 2 glucose transporter is the major carrier protein responsible for the reabsorption of glucose from the glomeruli back into the bloodstream. Empagliflozin improves glycemic control in patients with type 2 diabetes mellitus (type 2 diabetes) by reducing the reabsorption of glucose in the kidneys. The amount of glucose excreted by the kidneys through this mechanism depends on the concentration of glucose in the blood and the glomerular filtration rate (GFR). Inhibition of the sodium-dependent glucose transporter type 2 in patients with type 2 diabetes and hyperglycemia leads to the elimination of excess glucose by the kidneys.
In clinical studies, it was found that in patients with diabetes mellitus 2, the excretion of glucose by the kidneys increased immediately after the first dose of empagliflozin was applied; this effect lasted for 24 hours. The increase in glucose excretion by the kidneys was maintained until the end of the 4-week treatment period, averaging about 78 g / day with the use of empagliflozin at a dose of 25 mg once a day. In patients with type 2 diabetes, an increase in renal glucose excretion resulted in an immediate decrease in plasma glucose concentration.
Empagliflozin decreases plasma glucose concentration both in the case of fasting and after meals.
The insulin-independent mechanism of action of empagliflozin contributes to a low risk of possible development of hypoglycemia.
The effect of empagliflozin does not depend on the functional state of the beta cells of the pancreas and insulin metabolism. The positive effect of empagliflozin on surrogate markers of beta-cell function, including the HOMA-ß index (model for assessing homeostasis-B) and the ratio of proinsulin to insulin, was noted. In addition, the additional excretion of glucose by the kidneys causes a loss of calories, which is accompanied by a decrease in the volume of adipose tissue and a decrease in body weight.
Glycosuria, observed during the application of empagliflozin, is accompanied by a slight increase in diuresis, which can contribute to a moderate decrease in blood pressure.
In clinical studies where empagliflozin was used as monotherapy; combination therapy with metformin; combination therapy with metformin and sulfonylurea derivatives; combination therapy with metformin versus glimepiride; combination therapy with pioglitazone +/- metformin; in the form of a combination therapy with a dipeptidyl peptidase-4 inhibitor (DPP-4), metformin +/- another hypoglycemic oral drug; In the form of combination therapy with insulin, a statistically significant decrease in glycated hemoglobin HbAlc and a decrease in fasting plasma glucose concentration have been proven.

Pharmacokinetics

The pharmacokinetics of empagliflozin has been extensively studied in healthy volunteers and in patients with diabetes mellitus 2.

Suction

After oral administration of Jardiance, empagliflozin was rapidly absorbed, the maximum plasma concentration of empagliflozin (C max) was reached after 1.5 hours. Then the concentration of empagliflozin in plasma decreased in two phases.
After administration of empagliflozin, the average area under the concentration-time curve (AUC) during the period of steady concentration in the blood plasma was 4740 nmol x h / l, and the value of Cmax - 687 nmol / l.
The pharmacokinetics of empagliflozin in healthy volunteers and in patients with type 2 diabetes were, on the whole, similar.
Eating does not have a clinically significant effect on the pharmacokinetics of empagliflozin.

Distribution

The volume of distribution during the period of steady plasma concentration was approximately 73.8 liters. After oral administration of labeled empagliflozin [14C] to healthy volunteers, plasma protein binding was 86%.

Metabolism

The main metabolic pathway of human empagliflozin is glucuronidation with the participation of uridine-5'-diphospho-glucuronosyltransferase UGT2B7, UGT1A3, UGT1A8 and UGT1A9. The most commonly detected metabolites of empagliflozin are the three glucuronic conjugates (2-0, 3-0 and 6-0 glucuronide). The systemic effect of each metabolite is small (less than 10% of the total effect of empagliflozin).

Removal

The half-life was approximately 12.4 hours. In the case of empagliflozin once a day, a steady plasma concentration was reached after the fifth dose. After oral administration of labeled empagliflozin [14C], about 96% of the dose was eliminated in healthy volunteers (41% through the intestines and 54% through the kidneys). Through the intestines most of the labeled drug was excreted unchanged. Only half of the labeled drug was excreted by the kidneys in unchanged form.

Pharmacokinetics in Special Populations of Patients

Renal impairment

In patients with mild, moderate and severe severity of renal failure (30 <GFR <90 ml / min / 1.73 m2) and in patients with end-stage renal insufficiency, the AUC values ​​of empagliflozin increased, respectively, by about 18%, 20%, 66% and 48% compared with patients with normal renal function. In patients with moderate renal insufficiency and in patients with end-stage renal insufficiency, the maximum plasma empagliflozin concentration was similar to the corresponding values ​​in patients with normal renal function. In patients with mild to severe renal insufficiency, the maximum concentration of empagliflozin in plasma was about 20% higher than in patients with normal renal function. Population pharmacokinetic analysis data showed that the total clearance of empagliflozin decreased with decreasing GFR, which led to an increase in drug exposure.

Liver dysfunction

In patients with impaired liver function of mild, moderate and severe severity (according to Child-Pugh classification), the AUC values ​​of empagliflozin increased, respectively, by about 23%, 47% and 75%, and the values ​​of Stax, respectively, by about 4%, 23 % and 48% (compared with patients with normal liver function).
Body mass index, gender, race and age did not have a clinically significant effect on the pharmacokinetics of empagliflozin.

Children

Studies of the pharmacokinetics of empagliflozin in children have not been conducted.

Indications for use

Type 2 diabetes:
    as monotherapy in patients with inadequate glycemic control only on the background of diet and exercise, the appointment of metformin which is considered inappropriate because of intolerance;
    as a 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 for Jardiance

    Hypersensitivity to any component of the drug;
    Type 1 diabetes;
    Diabetic ketoacidosis;
    Rare hereditary disorders (lactase deficiency, lactose intolerance, glucose-galactose malabsorption);
    Renal failure with GFR <45 ml / min per 1.73 m2 (due to inefficiency);
    Pregnancy and breastfeeding period;
    Age over 85 years;
    Use in combination with analogues of glucagon-like peptide 1 (due to the lack of data on efficacy and safety);
    Children's age up to 18 years (due to the lack of data on efficacy and safety).

Carefully

    Patients at risk of developing hypovolemia (use of antihypertensive drugs with a history of arterial hypotension);
    In diseases of the gastrointestinal tract, leading to loss of fluid;
    Age over 75 years;
    Use in combination with sulfonylurea derivatives or insulin;
    Urogenital system infections.

Use Jardiance during pregnancy and during breastfeeding

The use of empagliflozin during pregnancy is contraindicated due to the lack of data on efficacy and safety.
The data obtained in preclinical studies in animals indicate the penetration of empagliflozin into breast milk. The risk of exposure to infants and children during breastfeeding is not excluded. The use of empagliflozin during breastfeeding is contraindicated. If necessary, the use of empagliflozin during breastfeeding, breast-feeding should be discontinued.

Dosage and administration

Monotherapy or combination therapy

The recommended initial dose of Jardiance is 10 mg (1 tablet dosage of 10 mg) once a day, by mouth.
If the 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.
The drug Jardiance can be taken regardless of the meal at any time of the day.

Actions to skip taking one or more doses of the drug

When you skip the dose, the patient should take Jardiance as soon as he remembers.
You should not take a double dose in one day.

Special patient groups

In case of renal failure with GFR from 45 to 90 ml / min / 1.73 m2, dose adjustment is not required.
In patients with renal insufficiency with GFR less than 45 ml / min / 1.73 m2, it is not recommended to use the drug due to inefficiency.
Patients with impaired liver function dose adjustment is not required.

Side effects

The overall incidence of adverse events in patients receiving empagliflozin or placebo was similar in clinical studies. The most common adverse reaction was hypoglycemia, which was observed when empagliflozin was used in combination with sulfonylurea or insulin derivatives (see the description of some undesirable reactions).
The adverse reactions observed in patients receiving empagliflozin in placebo-controlled studies are presented below in the Table (unwanted reactions were classified by organs and systems and in accordance with terms preferred by MedDRA) indicating their absolute frequency. Frequency categories are defined as follows: very frequent (> 1/10), frequent (from>; 1/100 to <1/10), infrequent (from> 1/1000 to <1/100), rare (from> 1 / 10,000 to <1/1000) or very rare (<1/10000); undesirable reactions are also highlighted, the frequency of which is unknown (cannot be estimated on the basis of available data).
Infectious and parasitic diseases - often - Vaginal candidiasis, vulvovaginitis, balanitis and other genital infections; Urinary tract infections.
Disorders of metabolism and nutrition - very often - hypoglycemia (when used together with sulfonylurea derivatives or insulin).
Disturbances from the kidneys and urinary tract - often - Frequent urination.
 Description of individual unwanted reactions

Hypoglycemia

The frequency of hypoglycemia depended on the concomitant hypoglycemic therapy used.
Mild hypoglycemia (blood glucose 3.0 to 3.8 mmol / l (54-70 mg / dL)) The incidence of mild hypoglycemia was similar in patients taking empagliflozin or placebo as monotherapy, as well as in the case of adding empagliflozin to metformin and in case of adding empagliflozin to pioglitazone (± metformin). When empagliflozin was prescribed in combination with metformin and sulfonylurea derivatives, the incidence of hypoglycemia was higher (10 mg: 10.3%; 25 mg: 7.4%) than when prescribed 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. When empagliflozin was prescribed in combination with metformin and sulfonylurea derivatives, the incidence of hypoglycemia was higher (10 mg: 5.8%; 25 mg: 4.1%) than with placebo in the same combination (3.1%).

Frequent urination

Frequency of frequent urination (symptoms such as pollakiuria, polyuria, nocturia) were higher in the case of empagliflozin (at a dose of 10 mg: 3.4%, at a dose of 25 mg: 3.2%) than in the case of placebo (1 %). The incidence of nocturia was comparable in the group of patients who took empagliflozin and in the group of patients who took 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 empagliflozin 25 mg and placebo (7.6%), but higher in the case of empagliflozin 10 mg (9.3%). As with placebo, urinary tract infections with empagliflozin were more common in patients with a history of chronic and recurrent urinary tract infections. The intensity of urinary tract infections was similar in patients taking empagliflozin and placebo. Urinary tract infections are more common in women.

Genital infections

The incidence of adverse events such as vaginal candidiasis, vulvovaginitis, balanitis and other genital infections was higher with empagliflozin (at a dose of 10 mg: 4.1%, at a dose of 25 mg: 3.7%) than with placebo (0 ,9%). Genital infections are more common in women. The intensity of genital infections was mild or moderate.

Hypovolemia

The incidence of hypovolemia (expressed as a decrease in blood pressure, orthostatic hypotension, dehydration, fainting) was similar in the case of empagliflozin (at a dose of 10 mg: 0.5%. At a dose of 25 mg: 0.3%) and placebo (0, 3%). In patients older than 75 years, the incidence of hypovolemia was comparable in patients taking empagliflozin at a dose of 10 mg (2.3%) and placebo (2.1%), but higher in patients who took empagliflozin at a dose of 25 mg (4.4% ).

Overdose

Symptoms

During controlled clinical trials, single doses of empagliflozin, reaching 800 mg (32 times the maximum daily dose) in healthy volunteers and multiple doses up to 100 mg (4 times the maximum daily dose) in patients with type 2 diabetes were well tolerated. The observed increase in urine volume did not depend on the magnitude of the dose and had no clinical significance. Experience of applying a dose in excess of 800 mg, no.

Treatment

In the case of overdose, it is recommended to remove the unabsorbed drug from the gastrointestinal tract, exercise clinical control and carry out symptomatic treatment.

Interaction with other drugs

Evaluation of drug interactions in vitro

Empagliflozin does not inhibit, does not inactivate and does not induce CYP450 isoenzymes. The main pathway of human metabolism of empagliflozin is glucuronidation with the participation of uridine-5'-diphospho-glucuronosyltransferase UGT2B7, UGT1A3, UGT1A8 and UGT1A9. Empagliflozin does not inhibit UGT1A1. Drug interactions of empagliflozin and drugs, which are substrates of CYP450 and UGT1A1 isoenzymes, are considered unlikely.
Empagliflozin is a substrate for the glycoprotein P (P-gp) and the protein that determines breast cancer resistance (BCRP). but in therapeutic doses does not inhibit these proteins. Based on the data obtained in in vitro studies, it is considered that the ability of empagliflozin to interact with drugs that are substrates for the glycoprotein P (P-gp) is unlikely. Empagliflozin is a substrate for organic anionic carriers: OATP, OATP1B1 and OATP1BZ, but is not a substrate for organic anionic carriers 1 (OAT1) and organic cationic carriers 2 (OCT2). However, drug interactions of empagliflozin with drugs, which are substrates for the above described carrier proteins, are considered unlikely.

Evaluation of drug interactions in vivo

The pharmacokinetics of empagliflozin do not change in healthy volunteers when combined with metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin, verapamil, ramipril, simvastatin, torasemide, and hydrochlorothiazide. When empagliflozin was used together with gemfibrozil, rifampicin and probenecid, the AUC value of empagliflozin increased by 59%, 35% and 53%, respectively, however, these changes were not considered clinically significant.
Empagliflozin has no clinically significant effect on the pharmacokinetics of metformin, glimepiride, pioglitazone, sitagliptin, linagliptin, warfarin. digoxin, ramipril, simvastatin, hydrochlorothiazide, torasemide and oral contraceptive drugs.

Diuretics

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

Insulin and drugs that increase its secretion

Insulin and secretion enhancing drugs, such as sulfonylurea derivatives, may increase the risk of hypoglycemia. Therefore, with simultaneous use of empagliflozin with insulin and drugs that increase its secretion, it may be necessary to reduce their dose, in order to avoid the risk of hypoglycemia.

special instructions

The drug Jardiance is not recommended for patients with type 1 diabetes and for the treatment of diabetic ketoacidosis.
The maximum daily dose of Jardiance contains 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 empagliflozin does not lead to an increase in cardiovascular risk. The use of empagliflozin in a dose of 25 mg does not lead to prolongation of the QT interval.
When combined use of the drug Jardiance with sulfonylurea derivatives or insulin may require a reduction in the dose of sulfonylurea / insulin derivatives due to the risk of hypoglycemia.
Not studied combination of hypoglycemic drugs
Empagliflozin has not been studied in combination with analogues of glucagon-like peptide 1 (GLP-1).

Kidney function monitoring

The effectiveness of the drug Jardiance depends on the function of the kidneys. Therefore, it is recommended to monitor kidney function before prescribing it and periodically during treatment (at least once a year), as well as before prescribing concomitant therapy, which may adversely affect kidney function. Patients with renal insufficiency (GFR less than 45 ml / min). taking the drug is not recommended.

Elderly patients

Patients aged 75 and over have an increased risk of dehydration. In these patients receiving empagliflozin, more often (compared to patients receiving placebo), adverse reactions caused by hypovolemia were observed. Experience with empagliflozin in patients older than 85 years is limited, therefore, it is not recommended to prescribe the drug Jardiance to patients over 85 years old.
Use in patients at risk of developing hypovolemia
According to the mechanism of action, taking the drug Jardiance can lead to a moderate decrease in blood pressure. Therefore, the drug should be used with caution in cases where a decrease in blood pressure is undesirable, for example, in patients with cardiovascular diseases; patients taking antihypertensive drugs (with a history of arterial hypotension), as well as in patients older than 75 years.
In the case of a patient taking the drug Jardiance. conditions that can lead to fluid loss (for example, in diseases of the gastrointestinal tract) develop, the patient’s condition, blood pressure, and hematocrit and electrolyte balance should be carefully monitored. It may require a temporary, up to the restoration of water balance, discontinuation of the drug.

Urinary tract infections

The incidence of side effects such as urinary tract infections was comparable when empagliflozin was used in a dose of 25 mg and placebo, and higher when empagliflozin was used in a dose of 10 mg. Complicated urinary tract infections (such as pyelonephritis and urosepsis) were observed with a similar frequency in patients taking empagliflozin and placebo. In the case of the development of complicated urinary tract infections, a temporary cessation of empagliflozin therapy is necessary.

Laboratory urine analysis

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

Influence on ability to drive vehicles and mechanisms

Clinical studies on the effect of empagliflozin on the ability to drive vehicles and mechanisms was not conducted. Patients should be careful when driving vehicles and machinery, since the use of the drug Jardiance (especially in combination with sulfonylurea derivatives and / or insulin) may develop hypoglycemia.

Release form

Film-coated tablets 10 mg, 25 mg.
On 10 tablets in PVC / Al the blister. 1 or 3 blisters along with instructions for use in a carton box.

Storage conditions

Store at a temperature not higher than 25 ° С.
Keep out of the reach of children.
Shelf life - 3 years.
Do not take the drug after the expiration date.

Terms of sell

You can buy Jardiance without a prescription.