An Open-label Comparison of a New Generic Sevoflurane Formulation With Original Sevoflurane in Patients Scheduled for Elective Surgery Under General Anesthesia

Abstract

PurposeTo compare the stability, effectiveness, and safety profiles of a new generic sevoflurane with those of the original sevoflurane formulation in patients undergoing elective surgery. MethodsAn accelerated 3-month storage test was performed to evaluate the compositional changes in generic sevoflurane stored in glass bottles. In addition, 182 patients were randomly allocated to receive generic (n = 89 [54 men and 35 women]; mean [SD] age, 49.9 [11.6] years) or original (n = 93 [61 men and 32 women]; mean [SD] age, 49.6 [11.1] years) sevoflurane at a gas flow of 3 L/min for approximately 3 hours. The mean minimum alveolar concentration (MAC) during sevoflurane anesthesia was evaluated, and gas samples for measuring compound A were collected from the inspiratory limb of the circuit at preset intervals. Blood samples for measuring serum inorganic fluoride were obtained at preset intervals (pharmacokinetic group: generic/original sevoflurane = 45/46). Renal biomarkers, such as N-acetyl-β-glucosaminidase, α- and π-glutathione-S-transferase, albumin, urine protein and osmolality, serum creatinine and osmolality, creatinine clearance, and blood urea nitrogen, were measured at preset intervals (renal biomarker group: generic/original sevoflurane = 44/47). Adverse reactions were monitored for 72 hours after discontinuation of sevoflurane use. FindingsGeneric sevoflurane contained in glass bottles was stable for 3 months. The mean MAC was similar for generic and original sevoflurane (median [range], 0.93 [0.67–1.29] vs 0.94 [0.63−1.5] vol%). Adverse event rates were similar (90.3% vs 84.3%), as were the AUClast of inorganic fluoride (333.7 [112.7−1264.7] vs 311.9 [81.5−1266.5] hours·μmol/L) and compound A (51.8 [6.3−204.5] vs 55.3 [10.8−270.6] hours·ppm). Biomarkers associated with renal injury were not significantly different between the 2 formulations. ImplicationsNo significant difference was found in the mean MAC between generic and original sevoflurane. ClinicalTrials.gov identifier: NCT01096212.