Pharmacovigilance of Sodium

Background: Postmarketing surveillance had previously identified the need for revisions in the labeling of the sodium-glucose cotransporter-2 (SGLT2) inhibitors drug class related to the risk of diabetic ketoacidosis. Other adverse events have been reported. Objective: To examine postmarketing surveillance data of the SGLT2 inhibitors, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, specifically to assess prevalence of urinary tract infections (UTIs) and genital fungal infections. Methods: FAERS case reports submitted between March 2013 and November 2015 were reviewed for 6 SGLT2 inhibitors (mono and combo therapies). The Medical Dictionary for Regulatory Activities (MedDRA) was used to define preferred terms (genital fungal infections: vulvovaginal mycotic infection, vulvovaginal candidiasis, urinary tract infection fungal, and genital candidiasis; UTI: urinary tract infection, genitourinary tract infection, kidney infection, cystitis, and pyelonephritis). Word frequencies were queried using the qualitative data analysis software NVivo 11 (QSR International), and results were then individually reviewed. Results: A total of 12 581 cases were received, but 466 were excluded (total n = 12 115). A total of 348 cases related to genital fungal infections were reported (2.9% of reports submitted): dapagliflozin = 53, empagliflozin/linagliptin = 6, canagliflozin = 267, canagliflozin/metformin = 3, empagliflozin = 17, and dapagliflozin/metformin HCl ER = 2. A total of 727 cases related to UTIs were reported (6% of reports submitted): dapagliflozin = 168, empagliflozin/linagliptin = 5, canagliflozin/metformin = 8, canagliflozin = 503, empagliflozin = 38, and dapagliflozin/metformin HCl ER = 5. Conclusions: A causal relationship between SGLT2 inhibitors and the adverse events reported cannot be established due to the nature of postmarketing surveillance. However, health care providers should counsel patients about these potential adverse events