Composition, form of production and packaging
The tablets covered with a film membrane of yellow color, capsule-shaped, with engraving on one of the sides "CFZ", and on the other - "100"; the core is white or almost white in cross section.
gangliflozin hemihydrate 102 mg,
which corresponds to the content of Kanagliflozin 100 mg
Excipients: microcrystalline cellulose - 39.26 mg, anhydrous - 39.26 mg, croscarmellose sodium - 12 mg, giprolose - 6 mg, magnesium stearate - 1.48 mg.
The composition of the film shell: dye Opaprai II 85F92209 yellow - 8 mg, including polyvinyl alcohol, partially hydrolyzed - 40%, titanium dioxide - 24.25%, macrogol 3350 - 20.2%, talc - 14.8%, iron oxide yellow - 0.75% .
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
The tablets covered with a film shell of white or almost white color, capsule-shaped, with engraving on one side of "CFZ", and on the other - "300"; the core is white or almost white in cross section.
gangliflozin hemihydrate 306 mg,
which corresponds to the content of cannagliflozin 300 mg
Excipients: microcrystalline cellulose - 117.78 mg, anhydrous lactose - 117.78 mg, croscarmellose sodium - 36 mg, giprolose - 18 mg, magnesium stearate - 4.44 mg.
The composition of the film shell: dye Opaprai II 85F18422 white - 18 mg, including polyvinyl alcohol, partially hydrolyzed - 40%, titanium dioxide - 25%, macrogol 3350 - 20.2%, talc - 14.8%.
10 pieces. - blisters (1) - packs of cardboard.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (9) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2015.
Mechanism of action
It was shown that in patients with diabetes there is increased renal glucose reabsorption, which can contribute to a steady increase in glucose concentration. Sodium-glucose cotransporter type 2 (SGLT2), expressed in the proximal renal tubules, is responsible for most of the glucose reabsorption from the tubule lumen.
Kanagliflozin is an inhibitor of sodium-glucose cotransporter type 2. Inhibiting SGLT2, cannagliflozin reduces the reabsorption of the filtered glucose and reduces the renal threshold for glucose (PPG), thereby increasing the excretion of glucose by the kidneys, which leads to a decrease in the concentration of glucose in the blood plasma with an insulin-independent mechanism in patients with type 2 diabetes. An increase in the excretion of glucose by the kidneys by inhibition of SGLT2 also leads to osmotic diuresis, a diuretic effect leads to a decrease in systolic blood pressure; increasing the excretion of glucose by the kidneys leads to a loss of calories and, as a result, a decrease in body weight.
In phase III studies, the use of cannaroglofosin 300 mg before meals resulted in a more pronounced decrease in postprandial increase in glucose concentration than when applied at a dose of 100 mg. This effect may be due in part to local inhibition of the intestinal SGLT1 transporter, taking into account transiently high concentrations of cannagliflozin in the lumen of the intestine prior to absorption of the drug (cannagliflozin is an inhibitor of SGLT1 with low activity). In studies, malabsorption of glucose was not detected with the use of cannagliflozin.
In clinical trials after single and multiple oral administration of cannagliflozin in patients with type 2 diabetes mellitus, the renal threshold for glucose was dose-dependent decreased, the excretion of glucose by the kidneys increased. The initial value of the renal threshold for glucose was about 13 mmol / L, the maximum decrease in the 24-hour mean renal glucose threshold was observed with the use of cannaroglobin at a dose of 300 mg 1 time / day and was 4 to 5 mmol / l, indicating a low risk hypoglycemia on the background of treatment. In a clinical study of the use of cannagliflozin in doses from 100 mg to 300 mg 1 time / day in patients with type 2 diabetes mellitus within 16 days, the decrease in the renal threshold for glucose and the increase in the excretion of glucose by the kidneys were constant. At the same time, the concentration of glucose in the blood plasma decreased dose-dependent on the first day of administration, followed by a steady decrease in fasting plasma glucose and after eating.
The use of cannagliflozin once in a dose of 300 mg before receiving mixed food in patients with type 2 diabetes mellitus caused a delay in the absorption of glucose in the intestine and a reduction in postprandial glycemia through renal and adrenal mechanisms.
In clinical trials, 60 healthy volunteers received a single oral oral gangliosin at a dose of 300 mg, kanagliflozin at a dose of 1200 mg (4 times the maximum recommended dose), moxifloxacin and placebo. No significant changes in the QT interval were observed, either with the use of cannaroglofosin at the recommended dose of 300 mg, nor with the use of cannagliflozin at a dose of 1200 mg. With the use of cannagliflozin in a dose of 1200 mg C max of the cannagliflozin in blood plasma was approximately 1.4 times higher than the maximum C ss after administration of cannaroglofosin at a dose of 300 mg 1 time / day.
In clinical trials, the use of cannagliflozin as monotherapy or supplementation to therapy with one or two oral hypoglycemic medications resulted in an average change in fasting glycemia from baseline versus placebo from -1.2 mmol / L to -1.9 mmol / L with the use of cannagliflozin at a dose of 100 mg and from -1.9 mmol / l to -2.4 mmol / l - with the use of cannagliflozin at a dose of 300 mg, respectively. This effect was close to the maximum after the first day of therapy and persisted throughout the treatment period.
In clinical studies of the use of cannagliflozin as monotherapy or adjunctive therapy, one or two oral hypoglycemic agents measured postprandial glycemia after a glucose tolerance test with a standardized mixed breakfast. The use of cannagliflozin led to an average decrease in the level of postprandial glycemia compared to baseline in relation to placebo from -1.5 mmol / L to -2.7 mmol / L - with the use of cannagliflozin at a dose of 100 mg and from -2.1 mmol / l to -3.5 mmol / l - with the use of cannagliflozin and a dose of 300 mg, respectively, due to a decrease in glucose concentration before meals and a decrease in the level of postprandial glycemia.
Function of? -cells
Studies of the use of cannagliflozin in patients with type 2 diabetes indicate an improvement in the function of ОІ-cells, according to the estimation of the homeostatic model-2 assessment index% B, HOMA2-% B, and an improvement in the rate of insulin secretion conducting a test of glucose tolerance with a mixed breakfast.
The pharmacokinetics of cannagliflozin in healthy subjects is similar to the pharmacokinetics of cannagliflozin in patients with type 2 diabetes mellitus. After a single dose of 100 mg and 300 mg of cannagliflozin in healthy volunteers, the cannagliflozin is quickly absorbed, the maximum plasma concentration (mean T max ) is reached after 1-2 hours. Plasma C max and AUC of cannagliflozin increased in a dose-proportional manner when the drug was administered in doses of 50 mg to 300 mg. The apparent final T 1/2 was 10.6 hours and 13.1 hours with the use of cannagliflozin at doses of 100 mg and 300 mg, respectively. The equilibrium state was achieved after 4-5 days after the initiation of therapy with cannaroglofosin in a dose of 100 mg or 300 mg 1 time / day.
Pharmacokinetics of cannagliflozin does not depend on time, the accumulation of the drug in the plasma reaches 36% after repeated administration.
The average absolute bioavailability of cannagliflozin is approximately 65%. Eating high-fat foods did not affect the pharmacokinetics of cannagliflozin; so can be taken with or without food. However, taking into account the ability of cannagliflozin to reduce the increase in postprandial glycemia due to a decrease in glucose absorption in the intestine, it is recommended to take cannaroglofosin before the first meal.
The average V d of the cannagliflozin in the equilibrium state after a single IV infusion in healthy individuals was 119 L, indicating a large distribution in the tissues.Kanagliflozin binds to a large extent with plasma proteins (99%), mainly with albumin. Binding to proteins does not depend on the concentration of cannagliflozin in plasma. Binding to plasma proteins does not significantly change in patients with renal or hepatic insufficiency.
O-glucuronation is the main pathway of the metabolism of cannagliflozin. Glucuronation occurs mainly with the participation of UGT1A9 and UGT2B4 to two inactive O-glucuronide metabolites. CYP3A4-mediated (oxidative) metabolism of cannagliflozna in the human body is minimal (about 7%).
After administration of a single dose of 14 C-cannagliflozin by orally healthy volunteers, 41.5%, 7% and 3.2% of the administered radioactive dose were detected in the stool as a cannagliflozin, hydroxylated metabolite, and O-glucuronide metabolite, respectively. The intestinal and hepatic circulation of cannagliflozin was insignificant.
Approximately 33% of the administered radioactive dose was detected in urine, mainly in the form of O-glucuronide metabolites (30.5%). Less than 1% of the dose is excreted in the form of unchanged kanagliflozin by the kidneys. Kidney clearance with the use of cannagliflozin in doses of 100 mg and 300 mg ranged from 1.30 to 1.55 ml / min.
Kanagliflozin belongs to drugs with low clearance, the average systemic clearance is approximately 192 ml / min in healthy individuals after IV introduction.
Special patient groups
Patients with impaired renal function
Renal failure did not affect C max of cannagliflozin. Compared with healthy volunteers, the serum AUC of cannagliflozin increased by approximately 15%, 29% and 53% in patients with mild, moderate and severe renal failure, respectively, but was the same in healthy volunteers and patients with terminal chronic renal failure (CRF) ). This increase in AUC of cannagliflozin was not regarded as clinically significant.
It is not recommended the use of cannagliflozin in patients with severe renal failure, terminal stage of chronic renal failure, patients on dialysis, It is not expected that kanagliflozin will be effective in these patients. Removal of cannagliflozin by dialysis was minimal.
Patients with impaired hepatic function
After the use of cannaroglofosin at a dose of 300 mg once in comparison with patients with normal liver function in patients with a violation of liver function class A on the scale Child-Pugh (violation of liver function of mild severity), the indices C max and AUC ? increased by 7% and 10%, respectively, and decreased by 4% and increased by 11%, respectively, in patients with impaired hepatic class B function on the Child-Pugh scale (a violation of the liver function of moderate severity).These differences are not regarded as clinically significant. Dose adjustments in patients with mild or moderate hepatic insufficiency are not required. Clinical experience of the drug in patients with severe impairment of liver function (class C on the scale Child-Pugh) is absent, therefore, the use of cannagliflozin in this group of patients is contraindicated.
Patients of advanced age (? 65 years)
According to the results of population pharmacokinetic analysis, age had no clinically significant effect on the pharmacokinetics of cannagliflozin.
Children (<18 years old)
Studies of the pharmacokinetics of cannagliflozin in children have not been conducted.
Other patient groups
Dose adjustments for sex, race / ethnicity or BMI are not required. These characteristics did not have a clinically significant effect on the pharmacokinetics of cannagliflozin, according to the results of the pharmacokinetic population analysis.
Diabetes mellitus type 2 in adults combined with diet and exercise to improve glycemic control as:
- as part of combination therapy with other hypoglycemic drugs, including insulin.
Kanagliflozin is recommended to be taken 1 time / day, preferably before breakfast.
Adults (? 18 years old)
The recommended dose of cannagliflozin is 100 mg or 300 mg 1 time / day; preferably before breakfast.
With the use of cannagliflozin as an adjunct to insulin therapy or agents that enhance its secretion (for example, derivatives of sulfonylureas), the possibility of using the above drugs at lower doses may be considered to reduce the risk of hypoglycemia.
Kanagliflozin has a diuretic effect. In patients who received diuretics, in patients with impaired renal function of moderate severity [with a glomerular filtration rate (GFR) from 30 to <60 ml / min / 1.73 m 2 ] or patients aged в‰Ґ75 years, there was a more frequent development of adverse reactions, associated with a decrease in intravascular volume (for example, postural dizziness, orthostatic hypotension or arterial hypotension). Thus, in these patients, the use of cannagliflozin in the initial dose of 100 mg 1 time / day is recommended. Patients with signs of hypovolemia are recommended to correct this condition before the beginning of treatment with cannagliflozin. In patients receiving kanagliflozin at a dose of 100 mg with good tolerability, which require additional control of glycemia, it is advisable to increase the dose to 300 mg.
If a dose is missed, the drug should be taken as soon as possible; However, do not take a double dose for one day.
Special categories of patients
Children and teenagers under the age of 18
Safety and effectiveness of the use of cannagliflozin in children and adolescents have not been studied.
Patients aged? 75 years in the the initial dose should be 100 mg 1 time / day. With a good dose tolerance of 100 mg to patients who need additional control of glycemia, it is advisable to increase the dose to 300 mg.
Impaired renal function
In patients with impaired renal function of mild degree (estimated glomerular filtration rate (GFR) from 60 to <90 ml / min / 1.73 m 2 ), dose adjustment is not required.
In patients with impaired renal function of moderate severity, the use of the drug in an initial dose of 100 mg 1 time / day is recommended. With a good dose tolerance of 100 mg, patients who need additional control of glycemia, it is advisable to increase the dose to 300 mg.
Kanagliflozin is not recommended for patients with severe renal dysfunction (GFR <30 mL / min / 1.73 m 2 ), terminal stage of chronic renal failure (CRF), or in dialysis patients, since it is expected that in these populations of patients cannagliflozin will be ineffective.
Data on undesirable reactions observed in clinical trials of 1 kanagliflozin with a frequency of? 2% are systematized relative to each of the organ systems, depending on the frequency of occurrence using the following classification: very frequent (? 1/10), frequent (? 1/100, <1/10), infrequent (? 1/1000, <1/100), rare (? 1 / 10,000, <1/1000).
Disorders from the digestive tract: frequent - constipation, thirst 2 , dry mouth.
Disorders from the kidneys and urinary tract: frequent - polyuria and pollakiuria 3 , mandatory urination, urinary tract infection 4 , urosepsis.
Violations from the genitals and breast: frequent - balanitis and balanoposthitis 5 , vulvovaginal candidiasis 6 , vaginal infections.
1 Including monotherapy and addition to metformin, metformin and sulfonylureas, as well as metformin and pioglitazone.
2 The category "thirst" includes the term "thirst", and this category also includes the term "polydipsia".
3 The category "polyuria or pollakiuria" includes the terms "polyuria", this category also includes the terms "increased volume of excreted urine", "nocturia".
4 The category of "urinary tract infection" includes the term "urinary tract infection", and also includes the terms "cystitis" and "kidney infections."
5 The category "balanitis or balanoposthitis" includes the terms "balanitis" and "balanoposthitis", as well as the terms "candidal balanitis" and "genital fungal infections."
6 The category "vulvovaginal candidiasis" includes the terms "vulvovaginal candidiasis", "vulvovaginal fungal infections", "vulvovaginitis" and the terms "vulvitis" and "genital fungal infections."
Other undesirable reactions that developed in placebo-controlled studies of cannagliflozin with a frequency of <2% were unwanted reactions associated with a decrease in intravascular volume (postural dizziness, orthostatic hypotension, arterial hypotension, dehydration and fainting), skin rash and urticaria.
Adverse reactions associated with a decrease in intravascular volume
The frequency of all unwanted reactions associated with a decrease in intravascular volume (postural dizziness, orthostatic hypotension, arterial hypotension, dehydration and fainting) was <2% when using cannagliflozin in doses of 100 mg and 300 mg.
According to the results of the generalized analysis, patients with "loop" diuretics, patients with moderate renal insufficiency (GFR from 30 to <60 ml / min / 1.73 m2 ) and patients в‰Ґ75 years of age had a higher incidence of these undesirable reactions . In conducting studies with respect to cardiovascular risks, incidence of serious adverse reactions associated with a decrease in intravascular volume at application kanagliflozina not increased, cases of discontinuation due to adverse reactions of this type have been infrequent.
Hypoglycemia when used as a supplement to insulin therapy or agents which enhance secretion
When applying kanagliflozina as an adjunct to therapy with insulin or sulfonylureas development of hypoglycemia were reported more frequently. This is consistent with the expected increase in the frequency of hypoglycemia in cases where the drug, the use of which is not accompanied by the development of this condition is added to insulin or drugs that increase its secretion (e.g., sulfonylurea).
Changes in laboratory parameters
Increases in serum potassium concentration
Cases increasing potassium concentration in serum (> 5.4 mEq / L and 15% higher than the initial concentration) were observed in 4.4% of patients receiving kanagliflozin 100 mg, 7% of patients receiving kanagliflozin 300 mg, and 4.8% of patients placebo. Occasionally noted a more pronounced increase in serum potassium concentration in patients with impaired renal function, moderate, in which before there was an increase of concentration of potassium and / or who received multiple drugs that reduce the excretion of potassium (potassium-sparing diuretics and ACE inhibitors). In general, increasing the concentration of potassium was transient and did not require special treatment.
Increasing the concentration of creatinine and the serum urea
During the first six weeks after initiation of treatment there was a slight increase in average creatinine concentration (<5%) with a commensurate decrease in GFR, whereupon there was a general trend of the return parameters to the original values. Within six weeks after initiation of therapy kanagliflozinom indicated a moderate increase in urea concentration (15-20%), then the indicator remained stable. Patients with impaired renal function moderate severity increasing the concentration of urea and creatinine was noted in 10-11% and approximately 12% of cases, respectively.
The proportion of patients with a significant decrease in GFR (> 30%) compared with baseline, was noted at any stage of treatment was 2% - when applying kanagliflozina 100 mg, 4.1% - by applying the drug in doses of 300 mg and 2.1% - with placebo. These GFR decline were often transient, and the end of the study a similar decline in GFR was seen in fewer patients. According to the combined analysis of patients with renal insufficiency moderate, the proportion of patients with a significant decrease in GFR (> 30%) compared with baseline, was noted at any stage of the treatment, it was 9.3% - in the application kanagliflozina 100 mg, 12.2% - when used in a dose of 300 mg, and 4.9% - with placebo.After discontinuation kanagliflozina these changes in laboratory parameters underwent a positive trend or returned to the original level.
Increased concentration of LDL
was observed a dose-dependent increase in the concentration of LDL in the application kanagliflozina. Mean changes in LDL percentage of the original concentration as compared with placebo groups were 0.11 mmol / L (4.5%) and 0.21 mmol / l (8%) at application kanagliflozina in doses of 100 mg and 300 mg, respectively. Mean baseline LDL concentration values were 2.76 mmol / l 2.70 mmol / l and 2.83 mmol / liter when using kanagliflozina in doses of 100 and 300 mg and placebo, respectively.
Increasing the concentration of hemoglobin
In applying kanagliflozina in doses of 100 mg and 300 mg of a slight increase in the mean percentage change in hemoglobin concentration from baseline levels (3.5% and 3.8%, respectively) compared to a slight decrease in the placebo group (-1.1%). There was a slight increase comparable average percentage change in red blood cell count and hematocrit from baseline. Most of the patients had an increased concentration of hemoglobin (> 20 g / l) occurred in 6% of patients receiving kanagliflozin 100 mg, in 5.5% of patients receiving kanagliflozin 300 mg, and 1% of patients receiving placebo . Most values remained in the normal range.
Reduction of serum uric acid
In applying kanagliflozina in doses of 100 mg or 300 mg there was a moderate decrease the average concentration of uric acid from baseline (-10.1% and -10.6%, respectively) compared with placebo, the application of which there was a slight increase in the average initial concentration of (1.9%) . Reduction of serum uric acid groups kanagliflozina was maximum or close to maximum at 6 weeks and persisted throughout therapy. It observed a transient increase in the concentration of uric acid in urine. According to the results of the combined analysis kanagliflozina application in doses of 100 mg or 300 mg it has been shown that the incidence of nephrolithiasis was not improved.
Security in the cardiovascular system
It showed no increase in cardiovascular risk when using kanagliflozina compared with the placebo group.
- hypersensitivity to kanagliflozinu or any excipient the formulation;
- Type 1 diabetes mellitus;
- diabetic ketoacidosis;
- severe renal failure;
hepatic failure of severe degree;
- the period of breastfeeding;
- Children and adolescence under 18 years.
PREGNANCY AND LACTATION
Kanagliflozina trials of pregnant women have been conducted. Animal studies do not indicate direct or indirect adverse toxic effects in the reproductive system.Application kanagliflozina contraindicated during pregnancy.
Do not use this kanagliflozina women during breastfeeding, since, according to the available pharmacodynamic / toxicological data obtained during pre-clinical studies kanagliflozin penetrates into breast milk.
APPLICATION FOR FUNCTIONS OF THE LIVER
Use of the drug in patients with severe renal insufficiency is contraindicated.
Patients with a violation of mild renal function (estimated glomerular filtration rate (GFR) from 60 to <90 mL / min / 1.73 m 2 ) dose adjustment is required. Patients with violation moderate renal gravity is recommended to use the drug in an initial dose of 100 mg 1 time / day. With good tolerance dose of 100 mg to patients who require additional glycemic control, it is useful to increase the dose up to 300 mg.
Kanagliflozin not recommended in patients with impaired renal function, severe (GFR <30 mL / min / 1.73 m 2 ), End-stage renal disease (ESRD) or in patients undergoing dialysis, since it is expected that it would be ineffective in these patient populations kanagliflozin.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use of the drug in patients with hepatic insufficiency, severe contraindicated.
APPLICATION FOR CHILDREN
The use of the drug in children and adolescents under the age of 18 is contraindicated.
APPLICATION IN ELDERLY PATIENTS
Patients aged в‰Ґ 75 years at an initial dose should be administered 100 mg 1 time / day. With good tolerance dose of 100 mg to patients who require additional glycemic control, it is useful to increase the dose up to 300 mg.
Application kanagliflozina in patients with type 1 diabetes have not been investigated, however its use is contraindicated in these patients.
Kanagliflozina use contraindicated in diabetic ketoacidosis, patients with terminal chronic renal failure (CRF) or patients on dialysis, as such treatment will not be effective in these clinical situations.
Carcinogenicity and mutagenicity
Preclinical data do not show a particular hazard for humans, according to the results of pharmacological safety studies, repeated dose toxicity, genotoxicity, reproductive and developmental toxicity.
Kanagliflozina influence on fertility has not been studied in humans. Influence on fertility in animal studies was observed.
Hypoglycemia while the use of other hypoglycemic drugs
has been shown that the use kanagliflozina as monotherapy or in addition to the hypoglycemic agents (the use of which is not accompanied by the development of hypoglycemia) rarely led to the development of hypoglycemia. It is known that insulin and hypoglycaemic agents, reinforcing its secretion (e.g., sulfonylurea derivatives) cause hypoglycaemia. In applying kanagliflozina as a supplement to insulin therapy or agents which increase its secretion (e.g., sulfonylureas), hypoglycemia frequency was higher than for placebo.
Thus, to reduce the risk of hypoglycemia, recommended insulin dose reduction or means reinforcing its secretion.
Reduced intravascular volume
Kanagliflozin diuretic effect by increasing glucose excretion by the kidneys, causing osmotic diuresis, which may lead to a decrease in intravascular volume. In clinical studies kanagliflozina increase in adverse reactions associated with a decrease in intravascular volume (e.g., postural dizziness, orthostatic hypotension or hypotension), frequently observed during the first 3 months when applying kanagliflozina 300 mg. For patients who may be more susceptible to adverse reactions associated with decreased intravascular volume, such as patients receiving "loop" diuretics, patients with moderate severity of renal function and patients aged в‰Ґ 75 years.
Patients should report clinical symptoms decrease in intravascular volume. These adverse reactions often led to the cessation of the application and often kanagliflozina while continuing reception kanagliflozina corrected changing circuit receiving antihypertensive drugs (including diuretics). In patients with decreased intravascular volume should provide a correction of this condition prior to initiating treatment kanagliflozinom.
AT During the first 6 weeks of treatment there were cases kanagliflozinom small average cut estimated glomerular filtration rate (GFR) due to a decrease in intravascular volume. Patients predisposed to a greater decrease in intravascular volume, as stated above, is sometimes observed over a significant decrease in GFR (> 30%) which was subsequently allowed and sometimes require treatment interruptions kanagliflozinom.
Fungal infection of the genitals
In clinical studies, the frequency of candidal vulvovaginitis (vulvovaginal including vulvovaginal and fungal infections) was higher in women who received kanagliflozin, compared with the placebo group. Patients with a history of vulvovaginal candidiasis treated kanagliflozinom therapy were more likely to develop the infection. Among patients treated with kanagliflozinom, at 2.3% showed more than one episode of infection. Most reports concerned the vulvovaginal candidiasis, the first 4 months after initiation of treatment kanagliflozinom, 0.7% of patients discontinued due to kanagliflozina vulvovaginal candidiasis. The diagnosis of vulvovaginal candidiasis is usually installed only on the basis of symptoms. observed efficacy of topical or oral antifungal therapy in clinical studies,prescribed by a doctor or taken independently on the background of ongoing therapy kanagliflozinom.
In clinical studies, Candida balanitis and balanoposthitis observed more frequently in patients treated kanagliflozinom in doses of 100 mg and 300 mg compared with placebo. Balanitis or balanoposthitis developed, primarily in men who do not produce circumcision, and often develops in men with balanitis or balanoposthitis history. In 0.9% of patients treated with kanagliflozinom, noted more than one episode of infection. 0.5% of patients discontinued due kanagliflozina candidal balanitis or balanoposthitis. In clinical studies, in most cases, the infection was treated with topical antifungal agents, a doctor or taken independently on the background of ongoing therapy kanagliflozinom. It reported rare cases of phimosis, sometimes cropping operation.
in the study of cardiovascular outcomes in 4327 patients with diagnosed cardiovascular disease or high cardiovascular risk of the incidence of occurrence of fractures was 16.3, 16.4 and 10.8 per 1,000 patient-years of use Invokana preparation В® at doses of 100 mg and 300 mg and placebo, respectively. An imbalance in relation to the prevalence of fractures appeared in the first 26 weeks of therapy. In the pooled analysis of other studies of the drug Invokana В® , which have included approximately 5800 patients with diabetes from the general population, the incidence of the occurrence of bone fractures was 10.8, 12.0 and 14.1 per 1000 patient-years of use of the drug Invokana В®in doses of 100 mg and 300 mg and placebo, respectively.
During the 104 weeks of treatment kanagliflozin not adversely affect pas bone mineral density.
Impact on the ability to drive vehicles and manage mechanisms
Ne it was found that kanagliflozin may affect the ability to drive and use machines. However, patients should be aware of the risk of hypoglycemia when used kanagliflozina as an adjunct to insulin therapy or drugs that increase its secretion, an increased risk of adverse reactions associated with a decrease in intravascular volume (postural dizziness), and a deterioration in the ability to manage vehicles and mechanisms in the development of adverse reactions.
It is not known cases of overdose kanagliflozina. Single doses kanagliflozina which reached 1600 mg in healthy individuals and 300 mg of 2 times / day for 12 weeks in patients with type 2 diabetes are usually well tolerated.
In the case of an overdose must exercise routine supportive measures, such as removing material is not sucked from the gastrointestinal tract, to carry out clinical observation and conduct maintenance treatment with the clinical condition of the patient. Kanagliflozin practically not output during a 4-hour dialysis