Drowsiness associated with a generic fixed-dose glibenclamide/metformin combination tablet

Abstract

Background: Currently, there is limited documentation on adverse reactions associated with generic fixed-dose combination antidiabetic drugs. Aim: The aim of this study was to report the incidental finding of drowsiness associated with brand substitution of a fixed-dose glibenclamide/metformin combination tablet. Methods: A prospective cross-over study was conducted among 84 patients previously treated with a stable dose of 320 mg gliclazide coadministered with 2000 mg metformin. Patients were switched to two tablets twice daily of originator or generic fixed-dose glibenclamide 2.5 mg/metformin 500 mg for 12 weeks. After 12 weeks, patients who received originator fixed-dose glibenclamide/metformin were switched to generic tablets, whereas patients who had received generic tablets were switched to originator tablets. Both groups were subsequently followed-up for another 12 weeks. Results: Six patients (7.14%) experienced drowsiness with generic fixed-dose glibenclamide/metformin but not with the originator tablets. The patients complained of being unable to perform normal activities unless they had a nap. Blood glucose levels during these symptoms in four of the patients were between 8.3 and 9.4 mmol/L. There were no significant changes in fasting plasma glucose (FPG) or HbA1c levels in any of the affected patients. One patient had a 9.3-mmol/L decrease in FPG, but the HbA1c was still within the normal range. Conclusion: The cases of drowsiness with generic fixed-dose glibenclamide/metformin were unlikely to be associated with hypoglycaemia.