Direct healthcare professional communication with updated information on the risk of diabetic ketoacidosis during treatment with SGLT2 inhibitors (Invokana*, Vokanamet*, Forxiga, Xigduo, Jardiance, Synjardy*)
AstraZeneca AB (local representative of marketing authorisation holder: AstraZeneca d.o.o.), Boehringer Ingelheim International GmbH (local representative of marketing authorisation holder: Boehringer Ingelheim Zagreb d.o.o.) and Janssen-Cilag International N.V. (local representative of marketing authorisation holder: Johnson & Johnson S.E. d.o.o.), in agreement with the Agency for Medicinal Products and Medical Devices of Croatia (HALMED) and the European Medicines Agency (EMA), have informed healthcare professionals of the latest recommendations regarding the risk of diabetic ketoacidosis during treatment with SGLT2 inhibitors [Invokana* (canagliflozin), Vokanamet* (canagliflozin/metformin), Forxiga (dapagliflozin), Xigduo (dapagliflozin/metformin), Jardiance (empagliflozin), Synjardy* (empagliflozin/metformin)]. This follows on the outcome of an evaluation of the risk of diabetic ketoacidosis during treatment with SGLT2 inhibitors.
- Rare but serious, sometimes life-threatening and fatal cases of diabetic ketoacidosis have been reported in patients on SGLT2 inhibitor treatment for 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 diabetic ketoacidosis in patients with diabetes could delay diagnosis and treatment.
- 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. Prescribers should inform patients of signs and symptoms of metabolic acidosis and advise them to immediately seek medical advice if they develop such signs and symptoms.
- In patients where diabetic ketoacidosis is suspected or diagnosed, treatment with SGLT2 inhibitors should be discontinued immediately.
- Restarting SGLT2 inhibitor treatment in patients with previous diabetic ketoacidosis while on SGLT2 inhibitor treatment is not recommended unless another clear precipitating factor is identified and resolved.
- Treatment should be interrupted in patients who are hospitalised for major surgical procedures or acute serious medical illnesses. In both cases, treatment with SGLT2 inhibitors may be restarted once the patient’s condition has stabilised.
- A substantial proportion of the cases concerned off-label use in patients with type 1 diabetes. Healthcare professionals are reminded that type 1 diabetes is not an approved indication for SGLT2 inhibitors.
- The letter provides additional recommendations to healthcare professionals related to factors that may predispose to ketoacidosis.
Sodium-glucose co-transporter-2 (SGLT2) inhibitors are medicines used to treat type 2 diabetes. They block a protein in the kidneys called SGLT2, which absorbs glucose back from the urine into the bloodstream as the blood is filtered in the kidneys. By blocking the action of SGLT2, these medicines cause more glucose to be removed through the urine, thereby reducing the levels of glucose in the blood.
Information for healthcare professionals contained in the summary of product characteristics (SmPC) as well as information for patients contained in the package leaflet (PL) will be updated with new information on the risk of diabetic ketoacidosis.
Here you may view the direct healthcare professional communication.
Healthcare professionals are reminded 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. HALMED recommends patients to contact their doctor or pharmacist regarding any adverse reaction they notice.
*The medicinal product has not been placed on the Croatian market or is not available on the Croatian market anymore