2016/05/16. Key messages

Transcription

1 Imprtant Safety Infrmatin n SGLT2 Inhibitrs [INVOKANA (canagliflzin), FORXIGA (dapagliflzin), XIGDUO (dapagliflzin/metfrmin), JARDIANCE (empagliflzin)] and the Risk f Diabetic Ketacidsis 2016/05/16 Audience Healthcare prfessinals including internal medicine specialists, endcrinlgists, cardilgists, nephrlgists, general r family practitiners, emergency healthcare prfessinals, critical care physicians, certified diabetes educatrs and pharmacists. Key messages Serius, smetimes life-threatening and fatal cases f diabetic ketacidsis (DKA) have been reprted in patients n sdium glucse ctransprter 2 (SGLT2) inhibitrs fr type 1 and type 2 diabetes. In a number f these cases, the presentatin f the cnditin was atypical with nly mderately increased bld glucse levels bserved. SGLT2 inhibitrs are NOT indicated fr treatment f type 1 diabetes mellitus and shuld nt be used in type 1 diabetes. It is recmmended that: if DKA is suspected r diagnsed, treatment with SGLT2 inhibitrs shuld be discntinued immediately. SGLT2 inhibitrs shuld nt be used in patients with a histry f DKA. in clinical situatins knwn t predispse t ketacidsis (e.g. majr surgical prcedures, serius infectins and acute serius illness), cnsideratin be given t temprarily discntinuing SGLT2 inhibitr therapy. patients be infrmed f the signs and symptms f DKA and be advised t immediately seek medical attentin if they develp them. cautin be used befre initiating SGLT2 inhibitr treatment in patients with risk factrs fr DKA. The Canadian Prduct Mngraphs f these prducts will be updated t reflect this safety infrmatin. 1

2 What is the issue? Clinical trial and pst-market cases f DKA, a serius, life-threatening cnditin requiring urgent hspitalizatin have been reprted in patients with type 1 and type 2 diabetes mellitus n SGLT2 inhibitr treatment. In a number f these reprts, the presentatin f the cnditin was atypical with nly mderately increased bld glucse levels bserved. Such atypical presentatin f DKA in patients with diabetes culd delay diagnsis and treatment. Prducts affected Brand Name Medicinal Ingredients Manufacturer INVOKANA canagliflzin Janssen Inc. FORXIGA dapagliflzin AstraZeneca Canada Inc. XIGDUO dapagliflzin and metfrmin AstraZeneca Canada Inc. JARDIANCE empagliflzin Behringer Ingelheim (Canada) Ltd. Backgrund infrmatin Sdium glucse c-transprter type 2 (SGLT2) inhibitrs are a class f drugs indicated as ral antihyperglycemic agents fr the treatment f patients with type 2 diabetes. The underlying mechanism fr SGLT2 inhibitr-assciated ketacidsis is nt clearly established. DKA usually develps when insulin levels are t lw t prevent ketacid accumulatin. DKA ccurs mst cmmnly in patients with type 1 diabetes and is usually accmpanied by high bld glucse levels (>14 mml/l). Hwever, the cases referred t abve als cncern patients with type 2 diabetes and in a number f cases bld glucse levels were nly slightly increased, in cntrast t typical cases f DKA. The majrity f the patients described in the abve reprts required hspitalizatin. T date, many f them have ccurred during the first 2 mnths f treatment. In many cases, just befre r at the same time as the ketacidsis ccurred, patients experienced dehydratin, lw fd intake, weight lss, infectin, surgery, vmiting, a decrease in their insulin dse r pr cntrl f diabetes. A substantial prprtin f the cases cncerned use f SGLT2 inhibitrs in patients with type 1 diabetes. SGLT2 inhibitrs are NOT indicated fr treatment f type 1 diabetes mellitus. Infrmatin fr cnsumers Diabetic ketacidsis (DKA) is a serius cmplicatin f diabetes caused by lw insulin levels. Rare cases f this cnditin, including life-threatening and fatal nes, have ccurred in patients taking SGLT2 inhibitrs [INVOKANA (canagliflzin), FORXIGA (dapagliflzin), XIGDUO (dapagliflzin/metfrmin), JARDIANCE TM (empagliflzin)] fr type 1 and type 2 diabetes. 2

3 A number f these cases have been unusual, with patients having bld sugar levels that are nt as high as typically expected in DKA, which can lead t a delay in diagnsis and treatment. Patients taking any f these medicines shuld be aware f the symptms f DKA, including lss f appetite, nausea r vmiting, stmach pain, feeling very thirsty, rapid breathing, cnfusin, feeling unusual tiredness, a sweet smell t the breath, a sweet r metallic taste in the muth, r a different dur t urine r sweat. Patients shuld immediately seek medical advice if they develp any f these symptms. Patients shuld als infrm their healthcare prfessinal abut medical issues r factrs (see belw) that may predispse them t ketacidsis. SGLT2 inhibitrs are NOT indicated fr treatment f type 1 diabetes mellitus and shuld nt be used in type 1 diabetes. Infrmatin fr health care prfessinals Befre initiating treatment with SGLT2 inhibitrs, factrs in the patient histry that may predispse t ketacidsis shuld be cnsidered. These factrs include: patients n a very lw carbhydrate diet (as the cmbinatin may further increase ketne bdy prductin), an acute serius illness, pancreatic disrders suggesting insulin deficiency (e.g., type 1 diabetes, histry f pancreatitis r pancreatic surgery), sudden insulin dse reductin (including insulin pump failure), alchl abuse, cnditins that lead t severe dehydratin, hspitalizatin fr majr surgery r serius medical illness. SGLT2 inhibitrs shuld be used with cautin in these patients. In additin, patients shuld be infrmed f these risk factrs. SGLT2 inhibitrs shuld nt be used in patients with a histry f DKA. A substantial prprtin f the cases cncerned ff-label use in patients with type 1 diabetes. Prescribers are reminded that type 1 diabetes is NOT an apprved indicatin fr SGLT2 inhibitrs. Patients n SGLT2 inhibitrs shuld be tested fr ketnes when they present with symptms f acidsis in rder t prevent delayed diagnsis and patient management. If ketacidsis is suspected, treatment with SGLT2 inhibitrs shuld be discntinued. Prescribers shuld infrm patients f signs and symptms f metablic acidsis and advise them t immediately seek medical advice if they develp such signs and symptms. 3

4 Actin taken by Health Canada This cmmunicatin is a fllw-up t an Infrmatin Update published by Health Canada n June 22, 2015 ( Health Canada is currently wrking with the manufacturers t update the Canadian Prduct Mngraph t reflect this safety infrmatin. Reprt health r safety cncerns Managing marketed health prduct-related side effects depends n healthcare prfessinals and cnsumers reprting them. Any adverse event r ther serius r unexpected side effects t SGLT2 inhibitrs shuld be reprted t the apprpriate manufacturer (see Prducts affected ) r t Health Canada. Janssen Inc. Behringer Ingelheim (Canada) Ltd. 19 Green Belt Dr Suth Service Rd. Trnt, ON, M3C 1L9 Burlingtn, ON, L7L 5H4 Tel: Tel: 1 (800) Ext PV_lcal_Canada@behringer-ingelheim.cm AstraZeneca Canada Inc Middlegate Rad Mississauga, ON, L4Y 1M4 Tel: medinf.canada@astrazeneca.cm Yu can reprt any suspected adverse reactins assciated with the use f health prducts t Health Canada by: Calling tll-free at ; r Visiting MedEffect Canada's Web page n Adverse Reactin Reprting ( fr infrmatin n hw t reprt nline, by mail r by fax. Fr ther health prduct inquiries related t this cmmunicatin, cntact Health Canada at: Marketed Health Prducts Directrate mhpd_dpsc@hc-sc.gc.ca Telephne: Fax:

5 Sincerely, Original signed by Dr. Cathy Lau Vice President, Regulatry Affairs and Quality Management Janssen Inc. Dr. Neil Maresky, M.B., B.Ch., Vice President, Scientific Affairs AstraZeneca Canada Inc. Dr. Martina Flammer Vice President, Medical and Regulatry Affairs Behringer Ingelheim (Canada) Ltd. 5