About Invokana (canagliflozin) - After first line, take a firm line
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Safety & Tolerability

The safety profile of Invokana is derived from clinical experience in over 1,000,000 patients treated globally and an extensive programme of phase III clinical trials in over 10,000 patients 1,2

  • The safety of Invokana has been evaluated in 10,285 patients with type 2 diabetes, including 3,139 patients treated with Invokana 100mg and 3,506 patients treated with Invokana 300mg in 9 double-blind, controlled phase III clinical studies. 1

Low frequency of hypoglycaemia

  • The frequency of hypoglycaemia was low when Invokana was used as monotherapy or as an add-on to metformin in dual therapy. 1,3
  • The risk of hypoglycaemia is increased when used in combination with insulin or a sulphonylurea, and consideration should be given to reducing the dose of insulin or sulphonylurea to minimise this risk. 1

Most common adverse effects (AEs) are associated with Invokana’s mode of action 1

  • From a pooled analysis of four 26-week placebo controlled trials (n=2,313) the most commonly reported AEs were hypoglycaemia in combination with insulin or a sulphonyulrea, vulvovaginal candidiasis (thrush), urinary tract infection (UTI), and increase in urine volume and frequency. 1,4
  • To prevent dehydration, patients should be advised to maintain sufficient hydration to avoid any AEs possibly related to volume depletion. 1

Signal for increased risk of lower limb amputation (LLA) – absolute risk remains extremely low

  • A small increased risk of LLA was seen in the Invokana treatment group vs the placebo group in the CANVAS Programme. 5
  • This risk equates to an additional 0.29 amputations per 100 years of patient treatment vs placebo, 5 but has not been seen anywhere else across the 12 completed Phase III or IV canagliflozin clinical trials, which included more than 8,100 type 2 diabetes patients with low CV risk, nor in a real world evidence study in a more general population of patients with type 2 diabetes. 6,7,9
  • In patients with established CV disease there was significant increased risk of below-knee amputation in patients taking any SGLT-2 inhibitor versus non SGLT-2 inhibitors. 8 A review committee investigated the potential risk of LLA and concluded that all SGLT-2 inhibitors share the same mode of action and there is no confirmed mechanism that is Invokana-specific. Subsequently a warning of the potential increased risk of LLA (mostly affecting the toes) has been added to the SmPC for all SGLT-2 inhibitors, highlighting the importance of routine preventative foot care. 9

Diabetic ketoacidosis

  • Rare cases of diabetic ketoacidosis (DKA), including like threatening and fatal cases, have been reported with SGLT2 inhibitors, including Invokana. If DKA is suspected or diagnosed, treatment with Invokana should be discontinued immediately. 1
  1. Reference 1(3)
  2. Date on File: Canagliflozin_DoF_06@EP14_MI_HW_002_v5. The number of patients treated with canagliflozin in the US
  3. Lavalle-González FJ et al. Diabetologia 2013;56(12):2582-92
  4. Usiskin K et al. Post grad Med 2014;126(3):16-34
  5. Neal B et al. N Engl J Med 2017;377:644-57.DOI:10.1056/NEJMoa1611925
  6. Yuan z et al. Diabetes Obes Metab 2017; DOI:10.1111/dom.13115
  7. Reference 3(4)
  8. Udell JA et al. Circulation 2018;137:1450-59
  9. Reference 4(5)