Sodium-Glucose Cotransporter-2 Inhibitor-associated Euglycemic Diabetic Ketoacidosis: Lessons From a Case Series of 4 Patients Undergoing Coronary Artery Bypass Grafting Surgery.

BACKGROUND: Euglycemic diabetic ketoacidosis (DKA) is a potentially life-threatening adverse condition associated with use of sodium-glucose cotransporter-2 inhibitors (SGLT2i). This risk is further pronounced in the perioperative period. There is no consensus for when SGLT2i should be held preoperatively, and recommendations from various organizations have evolved from 1 day to 3 to 4 days in the latest American Diabetes Association guidelines. Further study of patients with perioperative euglycemic DKA is required to help clarify the optimal timing of preoperative discontinuation of SGLT2i agents. METHODS: In this retrospective, single-centre case series we examined 4 patients who developed postoperative euglycemic DKA after coronary artery bypass grafting, 3 of whom underwent semiurgent surgery. We characterized their clinical course, predisposing factors and treatment characteristics. RESULTS: The SGLT2i were held for 1 to 5 days preoperatively, with times since last dose before surgery being 54, 79, 80 and 151 hours. Surgery was semiurgent for 3 patients, and elective for 1 patient. Three patients were diagnosed with euglycemic DKA within 24 hours after surgery. The fourth patient developed euglycemic DKA on postoperative day 3 in the context of significant hypovolemia and exhibited potential signs of protracted SGLT2i action at 7 days since the last dose. CONCLUSIONS: The duration of SGLT2i action and risk for DKA is variable and complex. Providers should hold SGLT2i at least 3 days before elective major surgery, with potentially longer times in high-risk patients. Careful vigilance should be used for perioperative DKA development in all patients recently exposed to SGLT2i.

A review of pharmacokinetic drug-drug interactions with the anthelmintic medications albendazole and mebendazole.

Medications indicated for helminthes and other parasitic infections are frequently being used in mass populations in endemic areas. Currently, there is a lack of guidance for clinicians on how to appropriately manage drug interactions when faced with patients requiring short-term anthelmintic therapy with albendazole or mebendazole while concurrently taking other agents. The objective of this review was to systematically summarize and evaluate published literature on the pharmacokinetics of albendazole or mebendazole when taken with other interacting medications. A search of MEDLINE (1946 to October 2014), EMBASE (1974 to October 2014), International Pharmaceutical Abstracts (1970 to October 2014), Google, and Google Scholar was conducted for articles describing the pharmacokinetics of albendazole or mebendazole when given with other medications (and supplemented by a bibliographic review of all relevant articles). Altogether, 17 articles were included in the review. Studies reported data on pharmacokinetic parameters for albendazole or mebendazole when taken with cimetidine, dexamethasone, ritonavir, phenytoin, carbamazepine, phenobarbital, ivermectin, praziquantel, diethylcarbamazine, azithromycin, and levamisole. Cimetidine increased the elimination half-life of albendazole and maximum concentration (Cmax) of mebendazole; dexamethasone increased the area under the plasma concentration-time curve (AUC) of albendazole; levamisole decreased the Cmax of albendazole; anticonvulsants (phenytoin, phenobarbital, carbamazepine) decreased the AUC of albendazole; praziquantel increased the AUC of albendazole; and ritonavir decreased the AUC of both albendazole and mebendazole. No major interactions were found with ivermectin, azithromycin, or diethylcarbamazine. Future research is required to clarify the clinical relevance of the interactions observed.