Vokanamet

73 m2) The dose of glucose-lowering therapy with Vokanamet should be individualised on the basis of the patient’s current regimen, effectiveness, and tolerability, using the recommended daily dose of 100 mg or 300 mg canagliflozin and not exceeding the maximum recommended daily dose of metformin orally.

For patients inadequately controlled on maximal tolerated dose of metformin For patients not adequately controlled on metformin, the recommended starting dose of Vokanamet should provide canagliflozin dosed at 50 mg twice daily plus the dose of metformin already being taken or the nearest therapeutically appropriate dose.

4). For patients switching from separate tablets of canagliflozin and metformin For patients switching from separate tablets of canagliflozin and metformin, Vokanamet should be initiated at the same total daily dose of canagliflozin and metformin already being taken or the nearest therapeutically appropriate dose of metformin.

Dose titration with canagliflozin (added to the optimal dose of metformin) should be considered before the patient is switched to Vokanamet. In patients tolerating Vokanamet containing canagliflozin 50 mg who need tighter glycaemic control, increasing the dose to Vokanamet containing canagliflozin 150 mg may be considered.

4). 4). 8). 4 Special populations Elderly Because metformin is eliminated in part by the kidney and elderly patients are more likely to have decreased renal function, Vokanamet should be used with caution as age increases. Regular assessment of renal function is necessary to aid in prevention of metformin-associated lactic acidosis, particularly in elderly patients.

4). 3). An eGFR should be assessed before initiation of treatment with metformin containing products and at least annually thereafter. g. every 3-6 months. The maximum daily dose of metformin should preferably be divided into 2-3 daily doses.

73 m2. If no adequate strength of Vokanamet is available, individual monocomponents should be used instead of the fixed dose combination (see table 1). 73 m2 Metformin Canagliflozin 60-89 Maximum daily dose is 3,000 mg Dose reduction may be considered in relation to declining renal function.

Maximum total daily dose is 300 mg. 45-59 Maximum daily dose is 2,000 mg The starting dose is at most half of the maximum dose. Canagliflozin should not be initiated. Patients tolerating canagliflozin can continue use at a maximum total daily dose of 100 mg.

Canagliflozin Summary of the safety profile The safety of canagliflozin was evaluated in 22,645 patients with type 2 diabetes, including the evaluation of canagliflozin in combination with metformin in 16,334 patients. In addition, an 18-week double-blind, placebo-controlled phase 2 study with twice daily dosing (canagliflozin 50 mg or 150 mg as add-on therapy with metformin 500 mg) was conducted in 279 patients in which 186 patients were treated with canagliflozin as add-on therapy with metformin.

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).

, 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.

Lactic acidosis Lactic acidosis, a very rare but serious metabolic complication, most often occurs at acute worsening of renal function or cardiorespiratory illness or sepsis. Metformin accumulation occurs at acute worsening of renal function and increases the risk of lactic acidosis.

In case of dehydration (severe diarrhoea or vomiting, fever or reduced fluid intake), Vokanamet should be temporarily discontinued and contact with a healthcare professional is recommended. Medicinal products that can acutely impair renal function (such as antihypertensives, diuretics and non-steroidal anti-inflammatory drugs [NSAIDs]) should be initiated with caution in Vokanamet-treated patients.

5). Patients and/or care-givers should be informed of the risk of lactic acidosis. Lactic acidosis is characterised by acidotic dyspnoea, abdominal pain, muscle cramps, asthenia and hypothermia followed by coma. In case of suspected symptoms, the patient should stop taking Vokanamet and seek immediate medical attention.

35), increased plasma lactate levels (> 5 mmol/L) and an increased anion gap and lactate/pyruvate ratio. The risk of lactic acidosis must be considered in the event of non-specific signs such as muscle cramps with digestive disorders as abdominal pain and severe asthenia.

Patients with known or suspected mitochondrial diseases In patients with known mitochondrial diseases such as Mitochondrial Encephalopathy with Lactic Acidosis, and Stroke-like episodes (MELAS) syndrome and Maternally inherited diabetes and deafness (MIDD), metformin is not recommended due to the risk of lactic acidosis exacerbation and neurologic complications which may lead to worsening of the disease.

In case of signs and symptoms suggestive of MELAS syndrome or MIDD after the intake of metformin, treatment with metformin should be withdrawn immediately and prompt diagnostic evaluation should be performed. 6 Renal function Decreased renal function in elderly patients is frequent and asymptomatic.

5).