Dear Healthcare Professional Letter on the risk of diabetic ketoacidosis during the treatment with SGLT2 inhibitors (Invokana, Vokanamet*, Forxiga, Xigduo*, Jardiance*, Synjardy*)
10.07.2015
In agreement with the European Medicines Agency (EMA) and the Agency for Medicinal Products and Medical Devices (HALMED), AstraZeneca AB (marketing authorisation holder’s local representative: AstraZeneca d.o.o.), Boehringer Ingelheim International GmbH (marketing authorisation holder’s local representative: Boehringer Ingelheim Zagreb d.o.o.) and Janssen Cilag International N.V. (marketing authorisation holder’s local representative: Johnson & Johnson S.E. d.o.o.) would like to inform healthcare professionals on the risk of diabetic ketoacidosis during the treatment with SGLT2 inhibitors [Invokana (canagliflozin), Vokanamet* (canagliflozin/metformin), Jardiance* (empagliflozin), Synjardy* (empagliflozin/metformin)].
Summary
- Serious cases of diabetic ketoacidosis in that sometimes were life threatening have been reported in patients affected with type 2 diabetes and treated with SGLT2 inhibitors (canagliflozin, dapagliflozin and empagliflozin).
- In a certain number of reports the condition has been occurred atypically with only moderately increased blood glucose level. This atypical occurrence of diabetic ketoacidosis in patients with diabetes may delay the diagnosis and treatment.
- Patients treated with SGLT2 inhibitors should be tested on ketones in cases they develop acidosis to prevent the delay diagnoses and treatment.
- cases of diabetic ketoacidosis have been reported in patients with type 1 diabetes receiving SGLT2 inhibitors. Prescribers are reminded that type 1 diabetes is not an authorised indication for these medicines.
More information
Serious cases of diabetic ketoacidosis have been reported in patients treated with SGLT2 inhibitors, where some of them were life threatening and mostly required hospitalisation. Half of these cases appeared during the first two months of treatment. One third of cases was prescribed off-label in type 1 diabetic patients. In certain cases, immediately before or concomitantly with the occurrence of ketoacidosis, patients were accompanied by: dehydration, reduced food intake, weight loss, infection, surgery, vomiting, decreased insulin dose or poor diabetes control. In a certain number of cases, atypically moderately increased blood glucose levels, or glucose levels below 14 mmol/L (250 mg/dL) have been reported whereas hypoglycaemia has been reported in one case. There have been also cases of ketoacidosis soon after the discontinuation of the use of SGLT2 inhibitors. The mechanism of diabetic ketoacidosis occurrence associated with SGLT2 inhibitors has not been established.
Prescribers should inform patients on the signs and symptoms of metabolic acidosis (such as: nosea, vomiting, anorexia, abdominal pain, feeling very thirsty, difficulty breading, confusion, unusual tiredness and sleepiness) and advise them to seek medical attention, should they develop any such symptom or sign. The EMA continues to review the risk of diabetic ketoacidosis and any new advise will be promptly communicated.
Here you may view the Dear Healthcare Professional Letter.
We remind healthcare professionals that they should report any adverse reaction, as well as quality defect to HALMED. Patients who have developed any adverse reaction to medicinal product may report it directly to HALMED, with recommendation regarding any adverse reaction they discover to consult their doctor or pharmacist about the continuation of their therapy.
*The medicinal product has not been placed on the Croatian market
