Health Canada advised that clinical trial and post-market cases of diabetic ketoacidosis (DKA), a serious, life-threatening condition requiring urgent hospitalization have been reported in patients on sodium glucose co-transporter 2 (SGLT2) inhibitors for type 1 and type 2 diabetes. In a number of these reports, the presentation of the condition was atypical with only moderately increased blood glucose levels observed. Such atypical presentation of DKA in patients with diabetes could delay diagnosis and treatment.
SGLT2 inhibitors are a class of drugs indicated as oral antihyperglycemic agents for the treatment of patients with type 2 diabetes. The underlying mechanism for SGLT2 inhibitor-associated ketoacidosis is not clearly established. DKA usually develops when insulin levels are too low to prevent ketoacid accumulation. DKA occurs most commonly in patients with type 1 diabetes and is usually accompanied by high blood glucose levels (>14 mmol/L). However, the cases referred to above also concern patients with type 2 diabetes and in a number of cases blood glucose levels were only slightly increased, in contrast to typical cases of DKA.
The majority of the patients described in the above reports required hospitalization. To date, many of them have occurred during the first 2 months of treatment. In many cases, just before or at the same time as the ketoacidosis occurred, patients experienced dehydration, low food intake, weight loss, infection, surgery, vomiting, a decrease in their insulin dose or poor control of diabetes.
A substantial proportion of the cases concerned use of SGLT2 inhibitors in patients with type 1 diabetes. SGLT2 inhibitors are NOT indicated for treatment of type 1 diabetes mellitus.
It is recommended that:
• patients on SGLT2 inhibitors should be tested for ketones when they present with symptoms of acidosis in order to prevent delayed diagnosis and patient management.
• if DKA is suspected or diagnosed, treatment with SGLT2 inhibitors should be discontinued immediately.
• SGLT2 inhibitors should not be used in patients with a history of DKA.
• in clinical situations known to predispose to ketoacidosis (e.g. major surgical procedures, serious infections and acute serious illness), consideration be given to temporarily discontinuing SGLT2 inhibitor therapy.
• patients be informed of the signs and symptoms of DKA and be advised to immediately seek medical attention if they develop them.
• caution be used before initiating SGLT2 inhibitor treatment in patients with risk factors for DKA.
The Canadian Product Monographs of the products containing SGLT2 inhibitors will be updated to reflect this safety information.
Please refer to the following website in Health Canada for details:
http://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/../58404a-eng.php
In Hong Kong, there are two registered pharmaceutical products containing dapagliflozin, namely Forxiga Tablets 5mg (HK-63301) and 10mg (HK-63302) which are registered by AstraZeneca Hong Kong Ltd (Astra); two products containing canagliflozin, namely Invokana Tablets 100mg (HK-63499) and 300mg (HK-63500) which are registered by Johnson & Johnson (HK) Ltd (J&J); and six products containing empagliflozin, namely Jardiance Tablets 10mg (HK-64095) and 25mg (HK-64096), Jardiance Duo Tablets 12.5mg/850mg (HK-64240), 5mg/850mg (HK-64241), 12.5mg/1000mg (HK-64242) and 5mg/1000mg (HK-64243) which are registered by Boehringer Ingelheim (HK) Ltd (Boehringer). All products are prescription only medicines. Related news was previously issued by various overseas drug regulatory authorities, and was posted on the Drug Office website since 16 May 2015, with the last update posted on 19 April 2016.
On 9 July 2015, 10 July 2015 and 14 December 2015, J&J, Astra and Boehringer notified the Department of Health (DH) respectively that they had issued letters to inform local healthcare professionals on the risk of diabetic ketoacidosis with SGLT2 inhibitors. So far, DH has received two adverse drug reaction cases of ketoacidosis after taking SGLT2 inhibitors, involving dapagliflozin and canagliflozin respectively. As previously reported, the issue, together with the above Health Canada announcement, will be discussed by the Registration Committee of the Pharmacy and Poisons Board.
Ends/ Tuesday, May 17, 2016
Issued at HKT 13:00
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