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Active ingredients
Dapagliflozin
Release form
Pills
Composition
1 tablet contains: Dapagliflozin propanediol monohydrate 12.3 mg, which corresponds to the content of dapagliflozin 10 mg Auxiliary substances: microcrystalline cellulose - 171.45 mg, anhydrous lactose - 50 mg, crospovidone - 10 mg, silicon dioxide - 3.75 mg, magnesium stearate - 2.5 mg. : Opadry II yellow - 10 mg (polyvinyl alcohol partially hydrolyzed - 4 mg, titanium dioxide - 2.35 mg, macrogol 3350 - 2.02 mg, talc - 1.48 mg, iron dye yellow oxide - 0.15 mg).
Pharmacological effect
Oral hypoglycemic drug. Mechanism of action: Dapagliflozin is a potent (inhibition constant (Ki) 0.55 nM), a selective reversible inhibitor of type 2 sodium-glucose co-transporter (SGLT2). SGLT2 is selectively expressed in the kidneys and is not found in more than 70 other tissues of the body (including in the liver, skeletal muscles, adipose tissue, mammary glands, bladder and brain). SGLT2 is the main carrier involved in the process of glucose reabsorption in the renal tubules. The reabsorption of glucose in the renal tubules in patients with type 2 diabetes mellitus (type 2 diabetes) continues despite hyperglycemia. By inhibiting the renal transfer of glucose, dapagliflozin reduces its reabsorption in the renal tubules, which leads to the elimination of glucose by the kidneys. The result of dapagliflozin is a decrease in fasting and postprandial glucose concentrations, as well as a decrease in the concentration of glycosylated hemoglobin in patients with type 2 diabetes. Excretion of glucose (glucose effect) is observed already after the first dose of the drug, persists for the next 24 hours and lasts for the entire course of therapy. . The amount of glucose excreted by the kidneys due to this mechanism depends on the concentration of glucose in the blood and on the glomerular filtration rate (GFR). Dapagliflozin does not interfere with normal endogenous glucose production in response to hypoglycemia. The effect of dapagliflozin does not depend on insulin secretion and insulin sensitivity. In clinical studies of the drug Farxiga, there was an improvement in β-cell function (HOMA test, homeostasis model assessment). Excretion of glucose by the kidneys caused by dapagliflozin is accompanied by loss of calories and a decrease in body weight.Inhibition of sodium glucose cotransport by dapagliflozin is accompanied by weak diuretic and transient natriuretic effects. Dapagliflozin does not affect other glucose transporters that transport glucose to peripheral tissues and shows more than 1400 times greater selectivity to SGLT2 than to SGLTlI, as well as going to work on the current glucose to the peripheral tissues and peripheral tissues of the glucose to the peripheral tissues. Pharmacodynamics After dapagliflozin was taken by healthy volunteers and patients with type 2 diabetes, there was an increase in the number of oh glucose by the kidneys. When receiving dapagliflozin at a dose of 10 mg / day for 12 weeks, patients with type 2 diabetes took about 70 g of glucose / day by the kidneys (which corresponds to 280 kcal / day). In patients with type 2 diabetes who took dapagliflozin at a dose of 10 mg / day for a long time (up to 2 years), glucose excretion was maintained throughout the entire course of therapy. Excretion of glucose by the kidneys with dapagliflozin also leads to osmotic diuresis and an increase in urine volume. The increase in urine volume in patients with diabetes mellitus 2 who took dapagliflozin at a dose of 10 mg / day was maintained for 12 weeks and was approximately 375 ml / day. The increase in urine volume was accompanied by a small and transient increase in sodium excretion by the kidneys, which did not change the serum sodium concentration. A planned analysis of the results of 13 placebo-controlled studies demonstrated a decrease in systolic blood pressure (MAP) of 3.7 mm Hg. and diastolic blood pressure (DBP) at 1.8 mm Hg. at week 24 of dapagliflozin therapy at a dose of 10 mg / day compared with a decrease in SBP and DBP by 0.5 mm Hg. in the placebo group. A similar decrease in blood pressure was observed during 104 weeks of treatment. When using dapagliflozin at a dose of 10 mg / day in patients with type 2 diabetes with inadequate glycemic control and hypertension, receiving angiotensin II receptor blockers, ACE inhibitors, including in combination with another antihypertensive drug, there was a decrease in the glycated hemoglobin index by 3.1% and a decrease in GAD by 4.3 mm Hg. after 12 weeks of therapy compared with placebo.
Pharmacokinetics
Absorption After ingestion, dapagliflozin is rapidly and completely absorbed from the gastrointestinal tract and can be taken both during and outside the meal.Cmax of dapagliflozin in the blood plasma is usually achieved within 2 h after administration on an empty stomach. Cmax and AUC values increase in proportion to the dose of dapagliflozin. The absolute bioavailability of dapagliflozin when administered orally at a dose of 10 mg is 78%. Meal had a moderate effect on the pharmacokinetics of dapagliflozin in healthy volunteers. Eating high in fat reduced Cmax of dapagliflozin by 50%, extended Tmax in plasma by about 1 hour, but did not affect AUC compared to fasting. These changes are not clinically significant. The distribution of dapagliflozin binding to plasma proteins is approximately 91%. In patients with various diseases, for example, with impaired renal or liver function, this indicator has not changed. Metabolism Dapagliflozin is a C-linked glucoside, the aglycone of which is associated with glucose by a carbon-carbon bond, which ensures its stability against glucosidases. Dapagliflozin is metabolized to form mainly the inactive metabolite dapagliflozin-3-O-glucuronide. After ingestion of 50 mg of 14C-dapagliflozin, 61% of the dose taken is metabolized to dapagliflozin-3-O-glucuronide, which accounts for 42% of total plasma activity. on AUC0-12 h). Unchanged drug accounts for 39% of total plasma radioactivity. The shares of the other metabolites do not exceed 5% of the total plasma radioactivity. Dapagliflozin-3-O-glucuronide and other metabolites have no pharmacological action. Dapagliflozin-3-O-glucuronide is formed by the enzyme uridine diphosphate-glucuronosyltransferase 1A9 (UGT1A9), present in the liver and kidneys, and the cytochrome CYP isoenzymes are involved in metabolism to a lesser extent. dapagliflozin orally at a dose of 10 mg. Dapagliflozin and its metabolites are excreted mainly by the kidneys, and only less than 2% is excreted unchanged. After taking 50 mg of 14C-dapagliflozin, 96% of radioactivity was detected — 75% in urine and 21% in feces. Approximately 15% of the radioactivity found in feces was unchanged dapagliflozin. Pharmacokinetics in special clinical situations. Patients with impaired renal function.In the equilibrium state (average AUC), systemic exposure to dapagliflozin in patients with diabetes mellitus and mild, moderate or severe renal failure (determined by the yogexol clearance) was 32%, 60% and 87% higher than in patients with diabetes and normal function kidneys, respectively. The amount of glucose excreted by the kidneys during the day while taking dapagliflozin in an equilibrium state depended on the state of the kidney function. In patients with T2DM and normal renal function, and with mild, moderate, or severe renal insufficiency, 85, 52, 18, and 11 g of glucose, respectively, were removed per day. There were no differences in the binding of dapagliflozin with proteins in healthy volunteers and in patients with renal insufficiency of varying severity. It is not known whether hemodialysis affects the exposure of dapagliflozin. Patients with impaired liver function. In patients with mild or moderate hepatic insufficiency, the mean Cmax and AUC values of dapagliflozin were, respectively, 12% and 36% higher compared with healthy volunteers. These differences are not clinically significant, so adjusting the dose of dapagliflozin for mild and moderate hepatic insufficiency is not required. In patients with severe liver failure (Child-Pugh class C), the mean Cmax and AUC values of dapagliflozin were 40% and 67% higher, respectively, compared to healthy volunteers. Elderly patients (≥65 years). There was no clinically significant increase in exposure in patients under the age of 70 years (unless factors other than age were taken into account). However, an increase in exposure can be expected due to a decrease in renal function associated with age. Exposure data in patients over the age of 70 years is insufficient. In women, the average AUC in equilibrium is 22% higher than that in men. Race. There were no clinically significant differences in systemic exposure among representatives of the Caucasoid, Negroid, and Mongoloid races. Body mass. Marked lower values of exposure with increased body weight. Therefore, in patients with low body mass, there may be a slight increase in exposure, and in patients with increased body mass, a decrease in dapagliflozin exposure can be observed.However, these differences are not clinically significant.
Indications
Diabetes mellitus type 2 in addition to diet and exercise to improve glycemic control as: - monotherapy; - additions to therapy with metformin, sulfonylurea derivatives (including in combination with metformin), thiazolidinedione, dipeptidyl peptidase 4 inhibitors (DPP-4 ) (including in combination with metformin), insulin preparations (including in combination with one or two hypoglycemic preparations for oral administration) in the absence of adequate glycemic control on this therapy; - starting combi treatment with metformin, with the appropriateness of this therapy.
Contraindications
- type 1 diabetes; - diabetic ketoacidosis; - moderate to severe renal failure (GFR <60 ml / min / 1.73 m2) or end-stage renal failure; - hereditary lactose intolerance, lactase deficiency and glucose-galactose intolerance; - pregnancy - breastfeeding period; - children and adolescents under 18 years of age (safety and efficacy not studied); - patients taking loop diuretics, or with a reduced BCC, for example, due to acute diseases (such as gastrointestinal - intestinal diseases); - elderly patients aged 75 years and older (to start therapy); - increased individual sensitivity to any component of the drug.
Precautionary measures
With caution: severe liver failure, urinary tract infection, risk of reducing BCC, elderly patients, chronic heart failure, increased hematocrit.
Use during pregnancy and lactation
Due to the fact that the use of dapagliflozin during pregnancy has not been studied, the drug is contraindicated in this category of patients. If pregnancy is diagnosed, dapagliflozin therapy should be discontinued. It is not known whether dapagliflozin and / or its inactive metabolites penetrate into breast milk. Risk to newborns / babies cannot be excluded. Dapagliflozin contraindicated during breastfeeding.
Dosage and administration
Inside, regardless of the meal. - Monotherapy: The recommended dose of Farxiga is 10 mg once a day. - Combination therapy: The recommended dose of Farxiga is 10 mg once a day in combination with metformin. - Initial combination therapy with metformin: Recommended dose of Farxiga drug is 10 mg once a day,The dose of metformin is 500 mg once a day. In case of inadequate glycemic control, doses of metformin should be increased. Use in special groups of patients. Patients with impaired liver function. In cases of impaired liver function, mild or moderate severity does not need to adjust the dose of the drug. Patients with abnormal liver function is recommended initial dose of 5 mg. With good tolerance, 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 renal function, in patients with impaired renal function of moderate severity, the effectiveness of treatment is reduced, and in patients with severe disorders, most likely, is absent. The Farxiga drug is contraindicated in patients with moderate to severe renal insufficiency (creatinine clearance (CK) for mild renal impairment). No need to adjust the dose of the drug. Children. The safety and efficacy of dapagliflozin have not been studied in patients under the age of 18 (see section "Contraindications"). Elderly patients. Elderly patients do not need to adjust the dose. However, when choosing a dose, it should be borne in mind that this category of patients is more likely to have impaired renal function and the risk of a decrease in circulating blood volume (BCC). Since clinical experience with the drug in patients 75 years and older is limited, it is contraindicated in inat dapagliflozin therapy in this age group.
Side effects
Summary of safety profileIn a pre-planned analysis of pooled data, results from 12 placebo-controlled trials were included in which 1,193 patients took dapagliflozin at a dose of 10 mg and 1,393 patients received placebo. The overall incidence of adverse events (short-term therapy) in patients taking dapagliflozin at 10 doses mg was similar to that in the placebo group. The number of adverse events leading to discontinuation of therapy was small and balanced between treatment groups. The most frequent adverse events that led to the abolition of dapagliflozin therapy at a dose of 10 mg were an increase in the concentration of creatinine in the blood (0.4%), urinary tract infection (0.3%), nausea (0.2%), dizziness (0, 2%) and rash (0.2%).In one patient who took dapagliflozin, the development of an adverse event on the part of the liver was diagnosed with drug-induced hepatitis and / or autoimmune hepatitis. Hypoglycemia was the most common adverse reaction, depending on the type of basic therapy used in each study. The incidence of mild hypoglycemia episodes was similar in treatment groups, including placebo. The list of unwanted reactions in the form of a table The unwanted reactions reported in placebo-controlled clinical studies are listed below. None of them depended on the dose of the drug. The frequency of adverse reactions is presented as the following gradation: very often (≥1 / 10), often (≥1 / 100, Undesirable reactions in placebo-controlled studies (a). Infections and invasions: Often * - Vulvovaginitis, balanitis, and similar genital infections (b), (c). Urinary tract infection (b). Infrequently ** - Vulvovaginal itching. Metabolic and nutritional disorders: Very often - Hypoglycemia (when used in combination with a sulfonylurea derivative or insulin) (b) Infrequently ** - Decreased BCC (b), (e) Thirst. Violation gastrointestinal tract: Infrequently ** - Constipation. Disorders of the skin and subcutaneous tissues: Infrequently ** - Increased sweating. Disorders of the musculoskeletal system and connective tissue: Often * - Back pain. Disorders of kidney and urinary tract: Often * - Dysuria, Polyuria (d). Infrequently ** - Nocturia. Laboratory and instrumental data: Often * - Dyslipidemia (f), Increased hematocrit value (g). Infrequently ** - Increased concentration of creatinine in the blood . Increased urea concentration in the blood. (A) - The table presents data on the use of the drug up to 24 weeks (short-term therapy), regardless of whether you are taking an additional hypoglycemic drug. (B) - See the appropriate subsection below for more information. (C) - Vulvovaginitis, balanitis and similar infections of the genital organs include, for example, the following predetermined preferred terms: vulvovaginal fungal infection, vaginal infection, balanitis, fungal infection of the genital organs, vulvovag oral candidiasis, vulvovaginitis, candidal balanitis, genital candidiasis, infection of the genital organs, infection of the genital organs in men, infection of the penis,vulvitis, bacterial vaginitis, vulvar abscess. (d) - Polyuria includes preferred terms: pollakiuria, polyuria, and increased diuresis. (e) - Reduced bcc includes, for example, the following predetermined preferred terms: dehydration, hypovolemia, arterial hypotension. (f) - The average change in the following indicators in percent of baseline values in the dapagliflozin group of 10 mg and the 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) - The mean change in hematocrit from baseline values was 2.15% in the dapagliflozin 10 mg group compared to - 0.40% in the placebo group. * Marked ≥2% of patients taking dapagliflozin at a dose of 10 mg and ≥1% more often than in the placebo group. ** Marked in ≥0.2% of patients and ≥0.1% more often in more patients (at least by 3) in the dapagliflozin 10 mg group compared with the placebo group, regardless of the supplemental hypoglycemic drug. Description of some unwanted reactions S: Hypoglycemia. The incidence of hypoglycemia depended on the type of basic therapy used in each study. In studies of dapagliflozin as monotherapy, combination therapy with metformin for up to 102 weeks, the incidence of mild hypoglycemia was similar (decrease in bcc. Undesirable reactions associated with a decrease in bcc (including reports of dehydration, hypovolemia, or arterial hypotension) were noted in 0.8 % and 0.4% of patients taking dapagliflozin 10 mg and placebo, respectively; serious reactions were noted in vulvovaginitis, balanitis and similar infections of the genital organs. Vulvovaginitis, balanitis and similar inf Genital organs were diagnosed 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 therefore 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 history, they more often recurred. Urinary tract infections. Urinary tract infections are more often noted when applied and dapagliflozin 10 mg than for placebo (4.3% compared with 3.7%, respectively; see section "Special instructions").Most infections were mild or moderate; the initial course of standard therapy was effective, and therefore patients rarely discontinued dapagliflozin. These infections more often developed in women, and in patients with such infections in history, they more often recurred. Parathyroid hormone (PTH). A slight increase in serum PTH concentration was noted, 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 studies, the overall proportion of patients with malignant or unspecified tumors was similar in the dapagliflozin group (1, 47%) and the placebo / reference group (1.35%). According to animal studies, the drug did not show carcinogenic or mutagenic properties. When considering cases of the development of tumors of various organ systems, the relative risk associated with dapagliflozin was above 1 for some tumors (bladder, prostate gland, mammary gland) and below 1 for others (for example, blood and lymphatic system, ovaries, urinary system) , in general, without increasing the 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 causal relationship is assessed as unlikely. Since the numerical imbalance of breast, bladder and prostate tumors requires special attention, the study of this issue will be continued as part of post-registration studies. Older patients (≥65 years). Unwanted reactions associated with impaired renal function or renal failure are reported in 2 , 5% of patients who received dapagliflozin, and 1.1% of patients who received placebo, in the group of patients ≥65 years old (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, a decrease in the BCC, most often recorded as arterial hypotension, was observed in 1.5% and 0.4% of patients taking dapagliflozin and placebo, respectively (see the section "Special Instructions").
Overdose
Dapagliflozin is safe and well tolerated by healthy volunteers when taken once in doses up to 500 mg (50 times higher than the recommended dose). Glucose was determined in the urine after taking the drug (at least 5 days after taking a dose of 500 mg), while no cases of dehydration, arterial hypotension, electrolyte imbalance, or clinically significant effect on the QTc interval were detected. The incidence of hypoglycemia was similar to the frequency with placebo. In clinical studies in healthy volunteers and patients with T2DM who took the drug once in doses up to 100 mg (10 times higher than the maximum recommended dose) for 2 weeks, the incidence of hypoglycemia was slightly higher than when taking placebo, and did not depend on the dose . The incidence of adverse events, including dehydration or hypotension, was similar to the frequency in the placebo group, with no clinically significant, dose-dependent changes in laboratory parameters, including serum electrolyte and kidney function biomarkers. Treatment: in case of overdose, maintenance therapy is necessary, considering the condition of the patient. Removal of dapagliflozin using hemodialysis has not been studied.
Interaction with other drugs
Pharmacodynamic interactionDapagliflozin may enhance the diuretic effect of thiazide and loop diuretics and increase the risk of dehydration and arterial hypotension. Hypoglycemia may occur on the background of insulin and insulin secretion medications. Therefore, in order to reduce the risk of hypoglycemia when co-prescribing Farxiga preparation with an insulin preparation or a drug that increases insulin secretion, it may be necessary to reduce the dose of an insulin preparation or a drug that increases insulin secretion. During in vitro studies, dapagliflozin did not inhibit cytochrome P450 isoenzymes of CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, and did not induce shaft isozymes CYP1A2, CYP2B6 and CYP3A4.In this regard, the effect of dapagliflozin on the metabolic clearance of concomitant drugs that are metabolized by these isoenzymes is not expected. The effect of other drugs on dapagliflozin Interaction studies involving healthy volunteers, mainly 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. naming of dapagliflozin and rifampicin, an inducer of various active transporters and drug metabolizing enzymes, a decrease in systemic exposure (AUC) of dapagliflozin by 22%, with no clinically significant effect on the daily excretion of glucose by the kidneys. It is not recommended to adjust the dose of the drug. No clinically significant effect is expected when used with other inducers (for example, carbamazepine, phenytoin, phenobarbital). After a joint use of dapagliflozin and mefenamic acid (UGT1A9 inhibitor), a 55% increase in systemic exposure of dapagliflozin, but without a significant effect on the daily injection, was observed. . It is not recommended to adjust the dose of the drug. The effect of dapagliflozin on other drugs In studies of interactions with healthy volunteers who mainly took a single dose of the drug, dapagliflozin did not affect the pharmacokinetics of metformin, pioglitazone, sitagliptin, glimepiride, hydrochlorothiazide, white flowers, white flowers, pyoglitazone, sitagliptin, glimepirida, hydrochlorothiazide, white flowers, white flowers, pyoglitazone, citagliptin, glimepiride, hydrochlorothiazide, white flowers, white flowers. -gp) or warfarin (S-warfarin, CYP2C9 isoenzyme substrate), or on the anticoagulant effect, as assessed by MHO. The use of dapagliflozin in a single dose of 20 mg and simvastatin (CYP3A4 isoenzyme substrate) resulted in an increase of 19% AUC of simvastatin and 31% AUC of simvastatinic acid. Increasing the exposure of simvastatin and simvastatinic acid is not considered clinically significant. Other types of interaction The effects of smoking, diet, taking herbal preparations and drinking alcohol on the parameters of dapagliflozin pharmacokinetics have not been studied.
special instructions
Use in patients with impaired renal function. The effectiveness of dapagliflozin depends on kidney function, and this effectiveness is reduced in patients with moderately severe renal failure and is probably absent in patients with severe renal impairment. Among patients with moderate renal failure (CC <60 ml / min or estimated GFR <60 ml / min / 1.73 m2), a greater proportion of patients receiving dapagliflozin showed an increase in the concentration of creatinine, phosphorus, PTH, and arterial hypotension patients receiving placebo. Farxiga is contraindicated in patients with moderate to severe renal failure (CC <60 ml / min or estimated GFR <60 ml / min / 1.73 m2). Forsig's drug was not studied in severe renal failure (CC <30 ml / min or estimated GFR <30 ml / min / 1.73 m2) or end-stage renal failure. It is recommended to monitor kidney function as follows: - before starting therapy with dapagliflozin and at least 1 time per year thereafter; - prior to the initiation of concomitant medications that can reduce kidney function, and periodically afterwards; - in case of a renal failure close to moderate severity, at least 2-4 times a year. With a decrease in kidney function below QC <60 ml / min or estimated GFR <60 ml / min / 1.73 m2, dapagliflozin should be stopped. Use in patients with impaired hepatic function Limited data on the use of the drug in patients with impaired liver function were obtained in clinical studies. Exposure of dapagliflozin is increased in patients with severely impaired liver function. The use of patients with the risk of reducing the circadian blood volume to develop arterial hypotension and / or electrolyte imbalance In accordance with the mechanism of action, dapagliflozin increases diuresis, accompanied by a slight decrease in blood pressure. The diuretic effect may be more pronounced in patients with a very high concentration of glucose in the blood. Dapagliflozin is contraindicated in patients taking loop diuretics, or in patients with reduced BCC, for example, due to acute diseases (such as gastrointestinal diseases). Care should be taken in patientsfor which a decrease in blood pressure caused by dapagliflozin may pose a risk, for example, in patients with a history of cardiovascular diseases, in patients with a history of arterial hypotension, careful monitoring of BCC and elderly patients is recommended. When taking dapagliflozin electrolytes (for example, physical examination, measurement of blood pressure, laboratory tests, including hematocrit) against the background of associated conditions that may lead to a decrease in BCC. With a decrease in BCC, it is recommended to temporarily stop taking dapagliflozin before correcting this condition. Ketoacidosis Ketoacidosis was reported during post-marketing use of the drug, incl. diabetic ketoacidosis, in patients with type 1 and 2 diabetes mellitus, taking the drug Farxiga and other inhibitors of SGLT2, although a causal link has not been established. Forsigue is not indicated for the treatment of patients with type 1 diabetes. Patients taking Forsig's drug with signs and symptoms indicating ketoacidosis, including nausea, vomiting, abdominal pain, malaise, and shortness of breath, should be checked for ketoacidosis, blood below 14 mmol / l. If ketoacidosis is suspected, the possibility of canceling or temporarily discontinuing the use of Farxiga should be considered and the patient should be examined immediately. history of pancreas surgery), insulin dose reduction, caloric intake of food consumed or increased need for insulin due to and fektsy, disease or surgery, as well as alcohol abuse. Forsigus should be used with caution in these patients. Urinary System Infections When analyzing the combined data of dapagliflozin use for 24 weeks, urinary tract infections are more common with dapagliflozin at a dose of 10 mg compared with placebo. The development of pyelonephritis was noted infrequently, with a similar frequency in the control group.Excretion of glucose by the kidneys may be accompanied by an increased risk of developing urinary tract infections, therefore, when treating pyelonephritis or urosepsis, the possibility of temporary discontinuation of dapagliflozin therapy should be considered. Urosepsis and pyelonephritis. With post-marketing use of the drug, serious urinary tract infections have been reported, including urosepsis and pyelonephritis, requiring hospitalization of patients taking Farxiga and other SGLT2 inhibitors. Therapy with SGLT2 inhibitors increases the risk of developing urinary tract infections. Patients should be monitored for signs and symptoms of urinary tract infections and, if indicated, should be treated immediately. Elderly patients Older patients are more likely to have impaired kidney function and / or use antihypertensive drugs that can affect kidney function, such as