Index of drugs

In adult patients (18 years of age) with type 2 diabetes to improve glycemic control as a monotherapy when diet and exercise alone do not provide adequate glycemic control for patients who can not be given Metformin because of intolerance or contraindications; as a combination therapy with other glucose-lowering medicines (including insulin), when together with diet and exercise they do not provide adequate glycemic control.

1 tabl powl. contains 100 mg or 300 mg of canagliflozin in the form of canagliflozin heparin. The preparation contains lactose.

An antidiabetic drug. Active inhibitor of the SGLT2 transporter, which is selectively expressed in the renal tubules, responsible for the reabsorption of filtered Glucose from the lumen of the tubules. By inhibiting SGLT2, canagliflozin reduces the reabsorption of filtered glucose and decreases the renal threshold for glucose (X-ray) and thus increases UGE, which results in patients with type 2 diabetes in reducing elevated glucose in this non-insulin independent mechanism. The increase in UGE by SGLT2 inhibition also translates into osmotic diuresis, with an osmotic effect leading to a reduction in systolic blood pressure; increasing UGE is associated with calorie expenditure and weight loss. After a single oral dose of 100 mg and 300 mg to healthy people, canagliflozin is rapidly absorbed to achieve_max 1-2 h after administration. Apparent T_0,5 is 10.6 ± 2.13 h and 13.1 ± 3.28 h for 100 mg and 300 mg, respectively. Steady state is achieved after 4-5 days of dosing once a day. The average absolute bioavailability after oral administration is approximately 65%. Canagliflozin binds extensively to plasma proteins (99%), mainly to albumin. O-glucuronidation is the main metabolic pathway for the elimination of canagliflozin, which is mainly coupled to glucuronic acid with the participation of UGT1A9 and UGT2B4 to two inactive O-glucuronic metabolites. The metabolism of canagliflozin with the participation of CYP3A4 is minimal (about 7%). After oral administration of a single canagliflozin dose, 41.5%, 7% and 3.2% of the administered dose were given in the faeces as canagliflozin, a hydroxylated metabolite and an O-glucuronic metabolite. The enterohepatic circulation of the drug is negligible. Approx. 33% of the administered dose was excreted in the urine, mainly as O-glucuronic metabolites (30.5%). Less than 1% of the dose was excreted unchanged in urine.

Hypersensitivity to the active substance or any of the excipients.

The drug has not been studied in patients with type 1 diabetes - use is not recommended. The preparation should not be used to treat diabetic ketoacidosis due to lack of efficacy in this condition. The efficacy of canagliflozin depends on renal function and the effectiveness is reduced in patients with moderate renal impairment and possibly in patients with severe renal impairment. Canagliflozin should not be used in patients with severe or terminal renal failure and in patients with eGFR <45 ml / min / 1.73 m² or CrCl <45 ml / min. Canagliflozin should not be initiated in patients with eGFR <60 ml / min / 1.73 m² or CrCl <60 ml / min. In patients tolerating canagliflozin, in which eGFR persists permanently below 60 ml / min / 1.73 m² or CrCl below 60 ml / min, adjust and maintain a 100 mg dose once a day. Canagliflozin should be discontinued when the eGFR is permanently below 45 ml / min / 1.73 m² or CrCl permanently below 45 ml / min. The following observation of renal function is recommended: before canagliflozin is started, and then at least once a year; before starting the use of combination drugs that may reduce renal function and then periodically; when renal dysfunction is moderate, at least 2 to 4 times a year. If renal function decreases permanently - eGFR below 45 ml / min / 1.73 m² or CrCl <45 ml / min, canagliflozin should be discontinued. Due to the mechanism of action, canagliflozin, by increasing urinary glucose excretion (UGE), induces osmotic diuresis, which may reduce intravascular volume and blood pressure. Due to the increased risk of adverse reactions associated with excessive fluid loss, caution should be exercised in patients in whom canagliflozin-induced blood pressure reduction may be a risk for patients with cardiovascular disease, patients with eGFR <60 ml / min / 1.73 m², patients taking antihypertensive therapy with a history of hypotension, patients taking diuretics or elderly patients (≥ 65 years). During the first 6 weeks of canagliflozin treatment due to excessive fluid loss, a generally small mean reduction in eGFR was observed. In the above-described patients more prone to decrease in intravascular volume, there was sometimes a greater decrease in eGFR (> 30%), which then improved and was not very often the reason for discontinuation of canagliflozin. Patients should be advised to report symptoms of excessive fluid loss. Canagliflozin is not recommended for patients receiving loop diuretics, or for excessive fluid loss, e.g. due to an acute illness (such as gastroenteritis). In patients receiving canagliflozin, if conditions occur that may lead to excessive loss of fluids (such as stomach and intestinal diseases), close observation of volition is recommended (eg physical examination, blood pressure measurement, laboratory tests including kidney function tests) and electrolyte concentrations. in plasma. Temporary discontinuation of canagliflozin should be considered in patients who develop hypovolemia until the condition is corrected. If the use is discontinued, more frequent glucose monitoring should be considered. Caution should be exercised in patients with increased hematocrit at baseline. Elderly patients may have a higher risk of excessive fluid loss, are more often treated with diuretics and have kidney problems. In patients ≥75 years, side effects associated with excessive fluid loss were more commonly reported. In addition, greater decreases in eGFR were reported in these patients. During the use of the drug there is a risk of fungal genital infections in women and men (more often in patients with a history of fungal infections). Inflammation of the glans penis and foreskin occurred mainly in uncircumcised patients. In rare cases, phimosis was observed and circumcision was sometimes performed. Most genital fungal infections were treated with local antifungal agents prescribed by a physician or alone, while continuing canagliflozin therapy. Limited clinical data are available for patients with NYHA Grade III heart failure and no clinical trial data are available for patients with cannabiflozin NYHA class IV heart failure IV. It is not recommended for patients with severe hepatic impairment. The safety and efficacy of canagliflozin in children and adolescents under 18 years have not been established. The preparation contains lactose - should not be used in patients with rare hereditary galactose intolerance, lactase deficiency (Lappa type) or malabsorption of glucose-galactose.

The drug should not be used during pregnancy and breastfeeding. If pregnancy is diagnosed, canagliflozin should be discontinued.

Very common: hypoglycaemia in combination with insulin or a sulphonylurea, vulvo and vaginal candidiasis, fungal infections of the vulva and vagina, vulvovaginal inflammation, vaginal infection, vulvitis and genital fungal infections. Common: constipation, thirst, dry mouth, polydipsia, nausea, polyuria, pollakiuria, urgency of urination, nocturia and increased urine, urinary tract infection, cystitis, kidney infection and uterine sepsis, glans and / or foreskin of the penis, inflammation of the glans and genital infection of the genitals, dyslipidemia, increased hematocrit. Uncommon: dehydration, dizziness after repositioning, fainting, hypotension, orthostatic hypotension, rash, urticaria, bone fractures, increased blood creatinine, increased blood urea, increased potassium in the blood, increased blood phosphate. Adverse reactions associated with excessive fluid loss (dizziness associated with a change in body posture, orthostatic hypotension, hypotension) occur more often during the 300 mg dose and in the first 3 months of treatment. Increased frequency of adverse reactions associated with excessive fluid loss also occurs in elderly patients ≥75 years and in patients with baseline eGFR <60 ml / min / 1.73 m² or CrCl <60 ml / min. In addition, more cases of elevated levels of potassium and creatinine in plasma and blood urea nitrogen have been reported in these patients. In patients with moderate renal impairment, the incidence of increased plasma potassium was higher; the changes were transient and did not require special treatment.

Orally. Adults. The recommended starting dose is 100 mg once a day. For patients who tolerate 100 mg canagliflozin once daily with an eGFR ≥60 ml / min / 1.73 m² or CrCl ≥60 ml / min and require better glycemic control can increase the dose to 300 mg. Caution should be exercised when increasing the dose in patients ≥75 years old, patients with cardiovascular disease, or in other patients in whom the increase in diuresis by canagliflozin may be a risk. In patients showing excessive fluid loss, it is recommended to correct this condition before canagliflozin is started. When canagliflozin is used in combination with insulin or an insulin secretagogue (insulin secretagogue), such as a sulphonylurea, a lower dose of insulin or an insulin secretagogue should be considered to reduce the risk of hypoglycaemia. Elderly patients (≥ 65 years old) should consider renal function and the risk of excessive fluid loss. In patients with eGFR, 60 to <90 ml / min / 1.73 m² or CrCl from 60 to <90 ml / min do not need to adjust the dose. Canagliflozin should not be initiated in patients with eGFR <60 ml / min / 1.73 m² or CrCl <60 ml / min. In patients tolerating canagliflozin, in which eGFR persists permanently below 60 ml / min / 1.73 m² or CrCl below 60 ml / min, adjust and maintain a 100 mg dose once a day. Canagliflozin should be discontinued when the eGFR is permanently below 45 ml / min / 1.73 m² or CrCl permanently below 45 ml / min. Canagliflozin should also not be used in patients with end-stage renal failure or in dialysis patients. No dosage adjustment is required in patients with mild or moderate hepatic impairment. Use in patients with severe hepatic impairment is not recommended. If you forget to take a dose, take it as soon as you remember, but do not take two doses on the same day. The preparation should be taken once a day, preferably before the first meal of the day. The tablets should be swallowed whole.