Forsiga - instructions for use, dose, side effects, contraindications

Active substanceDapaglyflozinDapaglyflozin

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Forsiga

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BRISTOL-MIYERS SQUIPB USA

Dosage form: & nbsp

film-coated tablets

Composition:

One tablet, film-coated, 5 mg contains:

Active substance: dapagliflozin propanediol monohydrate 6,150 mg, in terms of dapagliflozin 5 mg

Excipients: cellulose microcrystalline 85.725 mg, lactose anhydrous 25,000 mg, crospovidone 5,000 mg, silicon dioxide 1,875 mg, magnesium stearate 1,250 mg; tablet shell: Opadrai® II yellow 5,000 mg (polyvinyl alcohol partially hydrolyzed 2,000 mg, titanium dioxide 1,177 mg, macrogol 3350 1,010 mg, talc 0,740 mg, iron oxide dye yellow 0.073 mg).

One tablet, film-coated, 10 mg contains:

Active substance: dapagliflozin propanediol monohydrate 12.30 mg, in terms of dapagliflozin 10 mg

Excipients: cellulose microcrystalline 171.45 mg, anhydrous lactose 50.00 mg, crospovidone 10.00 mg, silicon dioxide 3.75 mg, magnesium stearate 2.50 mg; tablet shell: Opadrai® II yellow 10.00 mg (polyvinyl alcohol partially hydrolyzed 4.00 mg, titanium dioxide 2.35 mg, macrogol 3350 2.02 mg, talc 1.48 mg, iron oxide dye yellow 0.15 mg).

Description:

The tablets covered with a film membrane, 5 mg:

Round biconvex tablets, covered with a film membrane of yellow color, engraved "5" on one side and "1427" on the other side. Film-coated tablets, 10 mg: The rhomboid biconvex tablets covered with a film membrane of yellow color, with engraving "10" on one side and "1428" on the other side.

Pharmacotherapeutic group:hypoglycemic agent for oral administration - inhibitor of sodium-dependent glucose transporter of type 2

ATX: & nbsp

A.10.B.X Other hypoglycemic drugs

A.10.B.X.09 Dapaglyflozin

Pharmacodynamics:

Dapagliflozin is a potent (inhibition constant (K;) of 0.55 nM), a selective reversible inhibitor of the sodium-glucose cotransporter of type 2 (SGLT2). SGLT2 is selectively expressed in the kidneys and is not found in more than 70 other body tissues (including liver, skeletal muscle, adipose tissue, mammary glands, bladder and brain). SGLT2 is the main carrier involved in the process of reabsorption of glucose in the renal tubules. Reabsorption of glucose in the renal tubules in patients with type 2 diabetes mellitus (DM 2) continues despite hyperglycemia. By inhibiting renal glucose transport, dapagliflozin reduces its reabsorption in the renal tubules, which leads to excretion of glucose by the kidneys.The result of dapagliflozin is reduction of glucose concentration, fasting and postprandial, and reduced glycosylated hemoglobin concentrations in patients with type 2 diabetes.

Excretion of glucose (glucosuric effect) is observed after the first dose of the drug, remains for the next 24 hours and continues throughout the therapy. The amount of glucose released by the kidney due to this mechanism depends on the concentration of glucose in the blood and on the glomerular filtration rate (GFR). Dapaglyflozin does not interfere with the normal production of endogenous glucose in response to hypoglycemia. The effect of dapagliflozin is independent of insulin secretion and insulin sensitivity. In clinical studies of the drug Forsig ™, there was an improvement in beta-cell function (HOMA test, homeostasis model assessment).

The excretion of glucose by the kidneys, caused by dapagliflozin, is accompanied by a loss of calories and a decrease in body weight. Inhibition dapagliflozin sodium-glucose cotransport is accompanied by a weak diuretic and natriuretic transient effects.

Dapagliflozin has no effect on other carriers of glucose,carrying glucose transport to peripheral tissues, and exhibits more than 1400 times greater selectivity to SGLT2 than to SGLT1, the main transporter intestine responsible for glucose uptake.

Pharmacodynamics

After taking dapagliflozin by healthy volunteers and patients with CD2, there was an increase in the number of glucose output by the kidneys. When taking dapagliflozin at a dose of 10 mg / day for 12 weeks, patients with CD2 approximately 70 jr glucose per day was excreted by the kidneys (which corresponds to 280 kcal / day). In patients with CD2 who were taking dapagliflozin in a dose of 10 mg / day for a long time (up to 2 years), the excretion of glucose was maintained throughout the course of therapy.

Excretion of glucose by the kidneys with dapagliflozin also leads to osmotic diuresis and an increase in the volume of urine. The increase in the volume of urine in patients with DM2, who took dapagliflozin at a dose of 10 mg / day, persisted for 12 weeks and was approximately 375 ml / day. The increase in the volume of urine was accompanied by a small and transient increase in the excretion of sodium by the kidneys, which did not lead to a change in the concentration of sodium in the blood serum.

Pharmacokinetics:

Absorption
After oral administration dapagliflozin quickly and completely absorbed in the gastrointestinal tract and can be taken both during meals and outside it. The maximum concentration of dapagliflozin in the blood plasma (Cmax) is usually achieved within 2 hours after taking an empty stomach. The values of Cmax and AUC (the area under the concentration-time curve) increase in proportion to the dose of dapagliflozin. Absolute bioavailability of dapagliflozin when administered in a dose of 10 mg is 78%. The intake of food had a moderate effect on the pharmacokinetics of dapagliflozin in healthy volunteers. Eating high-fat foods reduced Cmax of dapagliflozin by 50%, lengthened Tmax (time to reach maximum plasma concentration) by about 1 hour, but did not affect AUC in comparison with reception on an empty stomach. These changes are not clinically relevant.

Distribution
Dapagliflozin is approximately 91% bound to proteins. In patients with various diseases, for example, with impaired renal or hepatic function, this indicator did not change.

Metabolism
Dapaglyflozin is a C-linked glucoside whose aglycone is linked to glucose by a carbon-carbon bond, which ensures its resistance to glucosidases. Mean half-life of blood plasma (T1 / 2) in healthy volunteers was 12.9 hours after a single dose of dapagliflozin inside at a dose of 10 mg. Dapaglyflozin is metabolized with the formation, mainly, of the inactive metabolite dapagliflozin-3-O-glucuronide.

After oral administration of 50 mg ¹⁴C-dapagliflozin 61% of the dose is metabolized to dapagliflozin-3-O-glucuronide, which accounts for 42% of the total plasma radioactivity AUC0-12 h) - The unchanged drug accounts for 39% of the total plasma radioactivity. The fractions of the other metabolites separately do not exceed 5% of the total plasma radioactivity. Dapagliflozin-3-O-glucuronide and other metabolites do not have a pharmacological effect. Dapagliflozin-3-O-glucuronide is formed by the action of the enzyme uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9), present in the liver and kidneys, cytochrome isoenzymes CYP are less involved in metabolism.

Excretion
Dapagliflozin and its metabolites are excreted mainly by the kidneys, and only less than 2% is excreted unchanged. After taking 50 mg ¹⁴C-dapagliflozin found 96% of radioactivity - 75% in urine and 21% - in feces.Approximately 15% of the radioactivity found in the feces was accounted for unchanged dapagliflozin.

Pharmacokinetics in special clinical situations

Patients with impaired renal function

In the equilibrium state (average value AUC) Dapagliflozin systemic exposure in patients with type 2 diabetes and renal insufficiency mild, moderate or severe (determined by the clearance of iohexol) was 32%, 60% and 87% higher than that in patients with type 2 diabetes and normal renal function, respectively. The amount of glucose output by the kidneys during the day when receiving dapagliflozin in an equilibrium state dependent on the state of renal function. In patients with type 2 diabetes and normal renal function, and renal insufficiency, mild, moderate or severe in 85 hours excreted, 52, 18 and 11 g of glucose, respectively. There was no difference in the binding of dapagliflozin with proteins in healthy volunteers and in patients with renal failure of varying severity. It is not known whether hemodialysis affects the exposure of dapagliflozin.

Patients with impaired hepatic function

In patients with mild or moderate hepatic insufficiency, the mean values of Stax and AUC dapagliflozin were respectively 12% and 36% higher as compared with healthy volunteers.These differences are not clinically significant, therefore, no dose adjustment for dapagliflozin in mild to moderate hepatic insufficiency is required (see "Dosage and Administration"), In patients with severe hepatic insufficiency (Child-Pugh grade C), mean values Stakh and AUC dapagliflozin were 40% and 67% higher, respectively, compared with healthy volunteers.

Patients of advanced age (> 65 years)

There was no clinically significant increase in exposure in patients under the age of 70 (unless other factors other than age were taken into account). Nevertheless, we can expect an increase in exposure due to a decrease in kidney function associated with age. Data on exposure in patients over the age of 70 years are insufficient.

Floor

In women, the mean AUC in the equilibrium state is 22% higher than in men.

Race

Clinically significant differences in systemic exposure among representatives of the Caucasoid, Negroid and Mongoloid races have not been revealed.

Body mass

Lower values of exposure at increased body weight were noted.Therefore, in patients with low body weight, there may be some increase in exposure, and in patients with increased body weight, a decrease in the exposure of dapagliflozin. However, these differences are not clinically relevant.

Indications:

Diabetes mellitus type 2 in addition to diet and exercise to improve glycemic control as:

· monotherapy;

· additions to metformin therapy in the absence of adequate glycemic control in this therapy;

· starting combination therapy with metformin, with the advisability of this therapy.

Contraindications:

Increased individual sensitivity to any component of the drug.

Diabetes mellitus type 1.

Diabetic ketoacidosis.

Renal failure of moderate to severe severity (GFR <60 mL / min / 1.73 m) or terminal stage of renal failure.

Hereditary lactose intolerance, lactase deficiency and glucose-galactose intolerance.

Pregnancy and the period of breastfeeding.

Children under 18 years of age (safety and efficacy not studied).

Patients who take "loop" diuretics (see p.(See "Interaction with other drugs and other drug interactions"), or with a reduced volume of circulating blood, for example, due to acute diseases (such as gastrointestinal diseases).

Elderly patients aged 75 years and over (to start therapy).

Carefully:hepatic impairment of severe degree, urinary tract infection, risk of decreased circulating blood volume, elderly patients, chronic heart failure, increased hematocrit.

Pregnancy and lactation:

Due to the fact that the use of dapagliflozin during pregnancy has not been studied, the drug is contraindicated during pregnancy. In case of pregnancy diagnosis, dapagliflozin therapy should be discontinued.

It is not known whether the dapagliflozin and / or its inactive metabolites into breast milk. It is impossible to exclude the risk for newborns / infants. Dapaglyflozin contraindicated during breastfeeding.

Dosing and Administration:

Inside, regardless of food intake.

Monotherapy: the recommended dose of the drug Forsig is 10 mg once a day.

Combination therapy: The recommended dose of Forsig ™ is 10 mg once daily in combination with metformin.

Start combination therapy with metformin: the recommended dose of the drug Forsig ™ is 10 mg once a day, the dose of metformin is 500 mg once a day. In case of inadequate glycemic control, the dose of metformin should be increased.

Use in special patient groups

Patients with impaired hepatic function

If the liver function is mild or moderate, there is no need to adjust the dose of the drug. Patients with severe liver dysfunction are recommended an initial dose of 5 mg. With good tolerability, the dose can be increased to 10 mg (see the sections "Pharmacokinetics" and "Special instructions").

Patients with impaired renal function

The effectiveness of dapagliflozin depends on the function of the kidneys, in patients with impaired renal function of moderate severity, the effectiveness of treatment is reduced, and in patients with severe disorders - most likely, there is no. The drug Forsig ™ is contraindicated in patients with moderate to severe renal insufficiency (creatinine clearance <60 ml / min or GFR <60 ml / min / 1.73 m) or with end-stage renal failure (see.sections "Contraindications", "Side effects" and "Special instructions").

If there is a mild degree of renal dysfunction, there is no need to adjust the dose preparation.

Children

The safety and effectiveness of dapagliflozin in patients younger than 18 years of age has not been studied (see the section "Contraindications").

Elderly patients

In elderly patients, there is no need to adjust the dose of the drug. However, when choosing a dose, it should be borne in mind that in this category of patients, kidney dysfunction and the risk of a decrease in circulating blood volume (BCC) are more likely. Since the clinical experience of using the drug in patients 75 years of age and older is limited, it is contraindicated to start therapy with dapagliflozin in this age group.

Side effects:

Security Overview

A pre-planned analysis of pooled data included results from 12 placebo-controlled studies in which 1,193 patients were enrolled dapagliflozin in a dose of 10 mg and 1393 patients received a placebo.

The overall incidence of adverse events (short-term therapy) in patients taking dapagliflozin in a dose of 10 mg, was similar to that in the placebo group.The number of adverse events that led to the abolition of therapy was small and balanced between treatment groups. The most frequent adverse events leading to the abolition of dapagliflozin therapy at a dose of 10 mg were an increase in creatinine concentration in the blood (0.4%), urinary tract infection (0.3%), nausea (0.2%), dizziness (0, 2%) and rash (0.2%). One patient who took dapagliflozin, there was a development of an undesirable phenomenon on the part of the liver with a diagnosis of drug-induced hepatitis and / or autoimmune hepatitis. The most common adverse reaction was hypoglycemia, the development of which depended on the type of basic therapy used in each study. The incidence of episodes of mild hypoglycemia was similar in treatment groups, including placebo.

List of unwanted reactions in the form of a table

Below are the undesirable reactions observed in placebo-controlled clinical trials. None of them depended on the dose of the drug. The frequency of unwanted reactions is presented in the following gradation: very often (> 1/10), often (> 1/100, <1/10), infrequently (> 1/1000, <1/100), rarely (> 1/10000 , <1/1000), very rarely (<1/10000) and unspecified frequency (can not be estimated from the received data) Undesirable reactions in placebo-controlled trials^a

Class of systems and organs	Often	Often*	Infrequently**
Infections and invasions		Vulvovaginitis, balanitis and similar infections of the genital organs^b^,^c Urinary tract infection^b	Vulvovaginal itching
Metabolic and nutritional disorders	Hypoglycemia (when used in combination with a sulfonylurea compound or insulin)^b		Decrease of BCC^{b, e} Thirst
Disorders from the gastrointestinal tract			Constipation
Disturbances from the skin and subcutaneous tissues			Increased sweating
Disturbances from the musculoskeletal system and connective tissue		Backache
Disorders from the kidneys and urinary tract		Dysuria Polyuria^d	Nocturia
Laboratory and instrumental data		Dyslipidaemia^fIncrease in hematocrit^g	Increase in the concentration of creatinine in the blood Increase in the concentration of urea in the blood

^aThe table shows the application data for the drug to 24 weeks (short-term therapy, regardless of the use of an additional hypoglycemic drug.

^bSee the appropriate subsection below for more information. ^cVulvovaginitis, balanitis and similar infections of the genitals include, for example, the following predefined preferred terms: vulvovaginal fungus infection, vaginal infection, balanitis, fungal infection of genital organs vulvovaginal candidiasis, vulvovaginitis, candidal balanitis, genital candida: genital infection, genital infection in men , infection of the penis vulvitis, bacterial vaginitis, abscess vulva.

^dPolyuria includes the preferred terms: pollakiuria, polyuria, and diuresis.

^eReduction of bcc includes, for example, the following pre-defined preferences *: dehydration, hypovolemia, arterial hypotension.

^fThe mean change in the following values as a percentage of baseline values in the 10 mg dapagliflozin group and placebo group, respectively, was: total cholesterol 1.4% compared to -0.4%; cholesterol-HDL 5.5% compared with 3.8%; Cholesterol-LDL 2.7% compared with -1.9%; triglycerides-5.4% compared to -0.7%.

^g Mean changes in hematocrit values from baseline were 2.15% in the 10-mg dapagliflozin group compared with -0.40% in the placebo group.

* There were> 2% of patients taking dapagliflozin in a dose of 10 mg, and> 1% more often than in the placebo group.

**> 0.2% of patients were noted and> 0.1% more often and more patients (at least 3) had 10 mg of dapagliflozin compared with placebo, depending on the use of an additional hypoglycemic drug.

Description of individual adverse reactions

Hypoglycaemia

The incidence of hypoglycemia depended on the type of basic therapy used in each study.

In studies of dapagliflozin as monotherapy, combined therapy with metformin for up to 102 weeks, the incidence of episodes of mild hypoglycemia was similar (<5%) in treatment groups, including placebo. In all studies, episodes of severe hypoglycemia were noted infrequently, and their incidence was comparable between the dapagliflozin group and placebo.

Decrease of BCC

Undesirable reactions associated with reduced BCC (including reports of dehydration, hypovolemia, or hypotension) were noted in 0.8% and 0.4% of patients taking dapagliflozin 10 mg and placebo, respectively; Serious reactions were noted in <0.2% of patients, and they were comparable in the 10 mg dapagliflozin and placebo groups (see section "Specific guidance").

Vulvovaginitis, balanitis and similar infections of the genital organs

Vulvovaginitis, balanitis and similar infections of the genital organs were noted in 4.8% and 0.9% of patients taking dapagliflozin 10 mg and placebo, respectively. Most infections were mild or moderate; the initial course of standard therapy was effective, and patients rarely stopped taking dapagliflozin. These infections more often developed in women (6.9% and 1.5% with dapagliflozin and placebo, respectively), and in patients with such infections in the anamnesis they more often recurred.

Urinary Tract Infections

Urinary tract infections are more often noted with 10 mg dapagliflozin than with placebo (4.3% compared with 3.7%, respectively, see section "Specific guidance"). Most infections were mild or moderate; the initial course of standard therapy was effective, and patients rarely stopped dapagliflozin. These infections are more common in women, and in patients with such infections in the anamnesis they more often recur.

Parathyroid hormone (PTH)

There was a slight increase in serum PTH concentration, and to a greater extent in patients with higher initial PTH concentrations.Studies of bone mineral density in patients with normal renal function or mild renal dysfunction did not reveal bone loss during one year of therapy.

Malignant tumors

In clinical trials, the total proportion of patients with malignant or unspecified tumors was similar in the dapagliflozin group (1.47%) and placebo / comparator group (1.35%). According to animal studies, the drug did not show carcinogenic or mutagenic properties. When considering the incidence of tumors in various organ systems, the relative risk associated with dapagliflozin was greater than 1 for some tumors (bladder, prostate, mammary gland) and below 1 for others (eg blood and lymphatic system, ovaries, urinary system) , generally without an increased risk of developing tumors associated with dapagliflozin. The increased / decreased risk was not statistically significant for any organ system. Given the lack of information on the development of tumors in preclinical studies, as well as a short latent period between the first exposure of the drug and the diagnosis of the tumor, the cause-effect relationship is estimated as unlikely.Since the numerical imbalance of tumors of the mammary gland, bladder and prostate gland requires special attention, the study of this issue will continue as part of post-registration research.

Elderly patients (> 65 years old)

Undesirable reactions associated with impaired renal function or renal failure were reported in 2.5% of patients who received dapagliflozin, and in 1.1% of patients receiving placebo, in the group of patients> 65 years (see section "Special instructions"). The most common adverse reaction associated with impaired renal function was an increase in serum creatinine concentration. Most of these reactions were transient and reversible. Among patients aged> 65 years, the decrease in BCC, most often recorded as hypotension, was noted in 1.5% and 0.4% of patients taking dapagliflozin and placebo, respectively (see section "Special instructions").

Overdose:

Dapagliflozin is safe and well tolerated by healthy volunteers with a single dose of up to 500 mg (50 times the recommended dose). Glucose was determined in the urine after taking the drug (at least,within 5 days after taking the dose of 500 mg), with no cases of dehydration, hypotension, electrolyte imbalance, clinically significant effect on the interval QTc. The incidence of hypoglycemia was similar to that seen with placebo. In clinical studies in healthy volunteers and patients with diabetes who received the drug once in doses up to 100 mg (10 times the maximum recommended dose) for 2 weeks, the incidence of hypoglycemia was slightly higher than with placebo, and did not depend on the dose . The incidence of adverse events, including dehydration or arterial hypotension, was similar to that in the placebo group, with no clinically relevant, dose-dependent changes in laboratory parameters, including serum electrolyte concentration and kidney biomarkers.

In case of an overdose it is necessary to carry out maintenance therapy, taking into account the condition of the patient. The elimination of dapagliflozin by hemodialysis has not been studied.

Interaction:

Pharmacodynamic interaction

Diuretics

Dapagliflozin can enhance the diuretic effect of thiazide and loop diuretics and increase the risk of developingdehydration and arterial hypotension (see section "Special instructions").

Pharmacokinetic interaction

The metabolism of dapagliflozin is mainly carried out by glucuronide conjugation under the action of UGT1A9.

During the research in vitro dapagliflozin did not inhibit the isoenzymes of the cytochrome P450 system CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and did not induce isoenzymes CYP1A2, CYP2B6 or CYP3A4. In this regard, the effect of dapagliflozin on the metabolic clearance of concomitant drugs that are metabolized by the action of these isoenzymes is not expected.

The effect of other drugs on dapagliflozin
Studies of interactions involving healthy volunteers, mostly taking a single dose of the drug, showed that metformin, pioglitazone, sitagliptin, glimepiride, voglibose, hydrochlorothiazide, bumetanide, valsartan or simvastatin do not affect the pharmacokinetics of dapagliflozin. After the combined use of dapagliflozin and rifampicin, an inducer of various active transporters and enzymes metabolizing drugs, a decrease in systemic exposureAUC) of dapagliflozin by 22%, in the absence of a clinically significant effect on the daily excretion of glucose by the kidneys. It is not recommended to adjust the dose of the drug. Clinically significant effects when used with other inducers (eg, carbamazepine, phenytoin, phenobarbital) are not expected.

After the combined use of dapagliflozin and mefenamic acid (inhibitor UGT1A9) an increase of 55% in the systemic exposure of dapagliflozin, but without a clinically significant effect on the daily excretion of glucose by the kidneys. It is not recommended to adjust the dose of the drug.

Effect of dapagliflozin on other drugs

In studies of interactions involving healthy volunteers, who mostly took a single dose of the drug, dapagliflozin did not affect the pharmacokinetics of metformin, pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, bumetanide, valsartan, digoxin (substrate P-gp) or warfarin (S-warfarin, isoenzymatic substrate CYP2C9), or anticoagulant effect, estimated by the International Normalized Ratio (MHO). The use of a single dose of dapagliflozin 20 mg and simvastatin (substrate isoenzyme CYP3A4) led to an increase of 19% AUC simvastatin and 31% AUC simvastatinic acid. An increase in the exposure of simvastatin and simvastatin acid is not considered clinically significant.

Other interactions

The effect of smoking, diet, intake of herbal preparations and alcohol consumption on the parameters of the pharmacokinetics of dapagliflozin has not been studied.

Special instructions:

Use in patients with impaired renal function

The effectiveness of dapagliflozin depends on the function of the kidneys, and this effectiveness is reduced in patients with moderate renal insufficiency and, probably, is absent in patients with impaired renal function of a serious degree (see section "Method of administration and dose"). Among patients with moderate renal insufficiency (CC <60 ml / min or estimated GFR <60 ml / min / 1.73 m), a larger proportion of patients receiving dapagliflozin, there was an increase in the level of creatinine, phosphorus, parathyroid hormone and arterial hypotension, than in patients receiving placebo. The drug Forsig ™ is contraindicated in patients with moderate or severe renal insufficiency (CC <60 mL / min or GFR estimated <60 mL / min / 1.73 m).Forsig ™ has not been studied in patients with severe renal failure (CK <30 mL / min or GFR <30 mL / min / 1.73 m) or terminal renal failure.

It is recommended to monitor kidney function as follows:
before the beginning of therapy with dapagliflozin and at least once a year afterwards (see the sections "Dosing and Administration", "Side Effects", "Pharmacodynamics" and "F Armakokinetics");
before the start of taking concomitant medications that can reduce kidney function, and periodically afterwards;
if the kidney function is violated, close to the average severity, at least 2-4 times a year. With a decrease in renal function below the value of CC <60 ml / min or estimated GFR <60 ml / min / 1.73 m², you must stop taking dapagliflozin.

Use in patients with impaired hepatic function

In clinical trials, limited data on the use of the drug in patients with impaired liver function were obtained. The exposure of dapagliflozin is increased in patients with impaired hepatic function (see "Dosage and Administration", "Precautions" and "Pharmacokinetics").

Use in patients at risk of reducing BCC development of arterial hypotension and / or electrolyte imbalance

In accordance with the mechanism of action dapagliflozin increases diuresis, accompanied by a slight decrease in blood pressure (see the section "Pharmacodynamics"). Diuretic effect can be more pronounced in patients with very high concentration of glucose in the blood.

Dapagliflozin is contraindicated in patients taking "loop" diuretics (see "Interactions with Other Drugs and Other Drug Interactions") or patients with reduced BCC, for example, due to acute diseases (such as gastrointestinal diseases). Caution should be exercised in patients for whom a decrease in arterial pressure caused by dapagliflozin may pose a risk, for example, in patients with a history of cardiovascular disease, in patients with a history of hypotensive anemia, receiving antihypertensive therapy, or in elderly patients.

When taking dapagliflozin, careful monitoring of the condition of bcc and concentration of electrolytes is recommended (for example, physical examination,measurement of blood pressure, laboratory tests, including hematocrit) against the background of concomitant conditions that may lead to a decrease in BCC. With a decrease in bcc, a temporary discontinuation of dapagliflozin before the correction of this condition is recommended (see the "Side effect" section). Urinary tract infections When analyzing the combined data of dapagliflozin up to 24 weeks, infections of the urinary tract are more often noted with dapagliflozin at a dose of 10 mg compared with placebo (see the section "Side effect"). Development of pyelonephritis was noted infrequently, with a similar frequency in the control group. The excretion of glucose by the kidneys can be accompanied by an increased risk of urinary tract infections, therefore, in the treatment of pyelonephritis or urosepsis, consideration should be given to the temporary withdrawal of dapagliflozin therapy (see "Side effect").

Elderly patients

Older patients are more likely to have renal dysfunction and / or use of antihypertensive medications that can affect kidney function, such as angiotensin converting enzyme (ACE inhibitors) and angiotensin II receptor type (APA) receptor antagonists.For elderly patients, the same recommendations apply for renal dysfunction, as for all patient populations (see "Dosage and Administration", "Side-Effects" and "Pharmacodynamics"). In the> 65-year-old group, a larger proportion of patients who received dapagliflozin, unwanted reactions associated with impaired renal function or renal failure compared with placebo developed. The most common adverse reaction associated with impaired renal function was an increase in serum creatinine, most cases were transient and reversible (see "Side effect" section).

In elderly patients, the risk of a decrease in BCC may be higher, and diuretics are more likely. Among patients aged> 65 years, a larger proportion of patients who received dapagliflozin, undesirable reactions associated with a decrease in bcc were noted (see section "Side effect").

The experience of using the drug in patients aged 75 years and older is limited. It is contraindicated to start therapy with dapagliflozin in this population (see the sections "Dosing and Administration" and "Pharmacokinetics").

Chronic heart failure

Experience in the use of the drug in patients with chronic heart failure I-II functional class by classification NYHA limited, and in clinical trials dapagliflozin It was not used in patients with chronic heart failure III-IV functional class for NYHA.

Increase in hematocrit

When dapagliflozin was used, an increase in hematocrit was observed (see the "Side effect" section), and therefore care should be taken in patients with elevated hematocrit.

Evaluation of urinalysis results

Due to the mechanism of action of the drug, the results of a urine test for glucose in patients taking the drug Forsig ™ will be positive.

Effect on the ability to drive transp. cf. and fur:

Studies to study the effect of dapagliflozin on the ability to drive vehicles and mechanisms were not conducted.

Form release / dosage:

The tablets covered with a film membrane, 5 mg, 10 mg.

Packaging:

For 14 tablets in a blister of aluminum foil; 2 or 4 blisters in a cardboard box with instructions for use or 10 tablets in a perforated aluminum foil blister; 3 or 9 perforated blisters in a cardboard box with instructions for use.

The places of opening of the cardboard bundle are sealed with two protective transparent colorless stakers; on the middle part of each stacker, bounded by the lines of separation, a pattern is drawn in the form of a yellow grid.

Storage conditions:At temperatures not higher than 30 ° C, in places inaccessible to children.

Shelf life:3 years. Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002596

Date of registration:21.08.2014

The owner of the registration certificate:BRISTOL-MIYERS SQUIPB BRISTOL-MIYERS SQUIPB USA

Manufacturer: & nbsp

BRISTOL-MYERS SQUIBB Manufacturing Company Puerto Rico

Representation: & nbspBRISTOL-Majers SKVIBB, LLCBRISTOL-Majers SKVIBB, LLCRussia

Information update date: & nbsp21.08.2014

Illustrated instructions

Instructions

Forsiga (Forxiga)