Pancreatitis in tigecycline Phase 3 and 4 clinical studies

Abstract

Objectives: To examine the incidence of pancreatitis among subjects enrolled in the tigecycline clinical trial programme, summarize cases and examine concomitant use of other pancreatitis-causing medications. Methods: Subject data fromPhase 3 and 4 comparative tigecycline studies were included in the analysis; investigator-reported adverse events of 'pancreatitis', 'necrotizing pancreatitis' or 'pancreas disorder' were reviewed. Data were summarized and cases were reported. No statistical comparisons were made. The incidence of overall pancreatitis with 95% CIs was calculated. TheWilson score method was used to calculate CIs. Results: Nineteen subjects with investigator-determined pancreatitis were identified from the programme database, which included 3788 subjects treated with tigecycline and 3646 subjects treated with a comparator. There were 9 cases identified among the tigecycline-treated subjects [9 of 3788 (0.24%; 95% CI, 0.11-0.45)] and 10 cases among the comparator-treated subjects [10 of 3646 (0.27%; 95% CI, 0.13-0.50)]. The demographic characteristics of the subjects with pancreatitis were similar between treatment groups. The median duration of tigecycline therapywas8.0 days compared with 11.0 days of comparator treatment. Concomitant or priorexposure to a Badalov class I medication was evident in the majority of subjects who developed pancreatitis. A numerically higher number of tigecycline-treated subjects were exposed to furosemide prior to the onset of pancreatitis than comparator-treated subjects. Conclusions: Pancreatitis was uncommon in subjects treated with tigecycline, with an occurrence of,1%. Concomitant medications known to cause pancreatitis should be considered when prescribing tigecycline, but may not identify those at risk of developing pancreatitis. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.