Invokana

Posology The recommended starting dose of canagliflozin is 100 mg once daily. 4). For dose adjustment recommendations according to eGFR refer to table 1. 4). 4). 8). 4). Renal impairment For treatment of diabetic kidney disease as add on to standard of care (eg ACE-inhibitors or ARBs), a dose of 100 mg canagliflozin once daily should be used (see table 1).

Because the glycaemic lowering efficacy of canagliflozin is reduced in patients with moderate renal impairment and likely absent in patients with severe renal impairment, if further glycaemic control is needed, the addition of other anti-hyperglycaemic agents should be considered.

For dose adjustment recommendations according to eGFR refer to table 1. 73 m2) or CrCl (mL/min) Total daily dose of canagliflozin ≥ 60 Initiate with 100 mg. In patients tolerating 100 mg and requiring additional glycaemic control, the dose can be increased to 300 mg.

30 to < 60b Use 100 mg. < 30b, c Continue 100 mg for patients already taking Invokanad. Invokana should not be initiated. 2. b If further glycaemic control is needed, the addition of other anti hyperglycaemic agents should be considered c With urinary albumin/creatinine ratio ˃ 300 mg/g d Continue dosing until dialysis or renal transplantation.

Hepatic impairment For patients with mild or moderate hepatic impairment, no dose adjustment is required. 2). 2). 4). The safety and effectiveness of Invokana have not been established in children below 10 years of age. Method of administration For oral use Invokana should be taken orally once a day, preferably before the first meal of the day.

Tablets should be swallowed whole. If a dose is missed, it should be taken as soon as the patient remembers; however, a double dose should not be taken on the same day.

Summary of the safety profile The safety of canagliflozin was evaluated in 22,645 adult patients with type 2 diabetes, including 13,278 patients treated with canagliflozin and 9,367 patients treated with comparator in 15 double-blind, controlled phase 3 and phase 4 clinical studies.

A total of 10,134 adult patients were treated in two dedicated cardiovascular studies for a mean exposure duration of 149 weeks (223 weeks in CANVAS and 94 weeks in CANVAS-R), and 8,114 adult patients were treated in 12 double blind, controlled phase 3 and phase 4 clinical studies, for a mean exposure duration of 49 weeks.

In a dedicated renal outcomes study, a total of 4,397 adult patients with type 2 diabetes and diabetic kidney disease had a mean exposure duration of 115 weeks. The primary assessment of safety and tolerability was conducted in a pooled analysis (n = 2,313) of four 26-week placebo-controlled clinical studies (monotherapy and add-on therapy with metformin, metformin and a sulphonylurea, and metformin and pioglitazone) in adults.

, urinary frequency). 5% of male patients). 4). Tabulated list of adverse reactions Adverse reactions in table 2 are based on the pooled analysis of the placebo- and active-controlled studies described above. Adverse reactions reported from world-wide postmarketing use of canagliflozin are also included in this tabulation.

Adverse reactions listed below are classified according to frequency and system organ class. Frequency categories are defined according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000), very rare (< 1/10,000), not known (cannot be estimated from the available data).

4 and description of adverse reaction (AR) below. 4 and description of AR below. c See description of AR below. 4. e Safety data profiles from individual pivotal studies (including studies in moderately renally impaired patients; older patients [≥ 55 years of age to ≤ 80 years of age]; patients with increased CV- and renal-risk) were generally consistent with the adverse reactions identified in this table.

4). 2). , postural dizziness, orthostatic hypotension, hypotension) was reported, particularly with the 300 mg dose. 8). 2). 1). 2) - Prior to initiation of concomitant medicinal products that may reduce renal function and periodically thereafter.

73 m2) both with and without albuminuria in adult patients. While both groups of patients benefitted, patients with albuminuria may benefit more from treatment with canagliflozin. 1). 8). 8). Due to volume depletion, generally small mean decreases in eGFR were seen within the first 6 weeks of treatment initiation with canagliflozin in adults.

8). Patients should be advised to report symptoms of volume depletion. , due to acute illness (such as gastrointestinal illness). , physical examination, blood pressure measurements, laboratory tests including renal function tests), and serum electrolytes is recommended.

Temporary interruption of treatment with canagliflozin may be considered for patients who develop volume depletion while on canagliflozin therapy until the condition is corrected. If interrupted, consideration should be given to more frequent glucose monitoring.

Diabetic ketoacidosis Rare cases of diabetic ketoacidosis (DKA), including life-threatening and fatal cases, have been reported in patients treated with SGLT2 inhibitors, including canagliflozin. In a number of cases, the presentation of the condition was atypical with only moderately increased blood glucose values, below 14 mmol/L (250 mg/dL).

2). Risk of DKA appears to be higher in patients with moderately to severely decreased renal function who require insulin. The risk of diabetic ketoacidosis must be considered in the event of non-specific symptoms such as nausea, vomiting, anorexia, abdominal pain, excessive thirst, difficulty breathing, confusion, unusual fatigue or sleepiness.

Patients should be assessed for ketoacidosis immediately if these symptoms occur, regardless of blood glucose level. In patients where DKA is suspected or diagnosed, treatment with Invokana should be discontinued immediately. Treatment should be interrupted in patients who are hospitalised for acute serious medical illnesses.

1.