Update review of the safety of sodium-glucose cotransporter 2 inhibitors for the treatment of patients with type 2 diabetes mellitus.

INTRODUCTION: The safety profile of sodium-glucose cotransporter 2 (SGLT2) inhibitors has continued to evolve with the availability of data from clinical trial programs, post-marketing pharmacovigilance and dedicated cardiovascular outcome trials. AREAS COVERED: This article reviews the safety issues associated with the SGLT2 inhibitors canagliflozin, dapagliflozin, and empagliflozin, particularly the newer/emergent safety data related to US Food and Drug Administration statements regarding these three agents. EXPERT OPINION: The safety profile of SGLT2 inhibitors is well defined, and the adverse event profile is largely consistent with their mechanism of action. These well-recognized events include genital mycotic infections and volume-associated adverse events. Serious safety issues detected more recently with SGLT2 inhibitor therapy, such as bone fractures, pyelonephritis, urosepsis, and ketoacidosis, have been uncommon. A robust improvement in cardiovascular outcomes in patients with type 2 diabetes mellitus (T2DM) was recently demonstrated with empagliflozin. Given the glucose-lowering efficacy, low risk of hypoglycemia, and other benefits associated with SGLT2 inhibitor therapy, this class of oral glucose-lowering medication is a valuable addition to treatment options for T2DM, and may play an increasingly prominent therapeutic role as emerging data are revealed.

Clinically relevant safety issues associated with St. John's wort product labels.

BACKGROUND: St. John's wort (SJW), used to treat depression, is popular in the USA, Canada, and parts of Europe. However, there are documented interactions between SJW and prescription medications including warfarin, cyclosporine, indinavir, and oral contraceptives. One source of information about these safety considerations is the product label. The aim of this study was to evaluate the clinically relevant safety information included on labeling in a nationally representative sample of SJW products from the USA. METHODS: Eight clinically relevant safety issues were identified: drug interactions (SJW-HIV medications, SJW-immunosupressants, SJW-oral contraceptives, and SJW-warfarin), contraindications (bipolar disorder), therapeutic duplication (antidepressants), and general considerations (phototoxicity and advice to consult a healthcare professional (HCP)). A list of SJW products was identified to assess their labels. Percentages and totals were used to present findings. RESULTS: Of the seventy-four products evaluated, no product label provided information for all 8 evaluation criteria. Three products (4.1%) provided information on 7 of the 8 criteria. Four products provided no safety information whatsoever. Percentage of products with label information was: SJW-HIV (8.1%), SJW-immunosupressants (5.4%), SJW-OCPs (8.1%), SJW-warfarin (5.4%), bipolar (1.4%), antidepressants (23.0%), phototoxicity (51.4%), and consult HCP (87.8%). Other safety-related information on labels included warnings about pregnancy (74.3%), lactation (64.9%), discontinue if adverse reaction (23.0%), and not for use in patients under 18 years old (13.5%). The average number of a priori safety issues included on a product label was 1.91 (range 0-8) for 23.9% completeness. CONCLUSION: The vast majority of SJW products fail to adequately address clinically relevant safety issues on their labeling. A few products do provide an acceptable amount of information on clinically relevant safety issues which could enhance the quality of counseling by HCPs and health store clerks. HCPs and consumers may benefit if the FDA re-examined labeling requirements for dietary supplements.

Evaluation of presence of aspirin-related warnings with willow bark.

BACKGROUND: The dietary supplement willow bark, also known simply as willow, contains salicylates that may present a safety risk to people. Current regulations do not require willow bark to include any cautions on its label. OBJECTIVE: To evaluate the absence or presence of label warnings related to salicylates contained in willow bark to ascertain whether a potentially dangerous lack of information exists. METHODS: The label of each willow supplement and willow-containing product was assessed for the presence or absence of 3 warnings: (1) aspirin allergy/sensitivity, (2) use of anticoagulants or "blood thinners," and (3) children with flu-like symptoms or Reye's syndrome. Products from pharmacies and health food stores were targeted and their labels analyzed. A compilation of the identified products was used to conduct a similar evaluation of warnings from their Web sites. RESULTS: A total of 58 willow bark-containing and 12 single-ingredient willow bark products were assessed. Of the 70 products evaluated, only 8.6% listed a warning. The warning regarding aspirin sensitivity was present on 4.3%, Reye's syndrome was 2.9%, and interactions with anticoagulants/"blood thinners" was 4.3%. One product was labeled as aspirin-free. Percentages were lower on Web sites. CONCLUSIONS: There is a dearth of information regarding potential safety risks on the labels of willow bark and willow bark-containing products. Combination products containing willow bark may pose a greater danger to at-risk patients based on their sheer volume. Counseling of patients who take dietary supplements can improve the situation; however, it may ultimately take improved requirements for dietary supplement labeling to fully address this problem.