An Evaluation of the Effectiveness of Risk Minimization Measures for Tigecycline in the European Union

Abstract

Background Risk minimization measures (RMM) were implemented from February 2011 in the European Union to address risks of superinfection, off-label use and lack of efficacy associated with tigecycline. The objective of this study was to evaluate RMM effectiveness by describing prescription patterns among adults and children treated with any dose of tigecycline for any indication pre-and post-RMM implementation; incidence proportions of superinfection and lack of efficacy among adults treated with approved doses of tigecycline for complicated intraabdominal infection and complicated skin and soft tissue infection were also evaluated. Methods This was an observational, retrospective chartabstraction study, including charts from 777 patients (399 pre-RMM, 378 post-RMM) at 13 sites across Austria, Germany, Italy, Greece and the United Kingdom (UK). Potential superinfection and lack of efficacy cases among those using tigecycline for on-label indication, age, dose, and duration were adjudicated. The distribution of indications for tigecycline was analyzed overall (i.e. across both study periods) and stratified by study period. Numbers and incidence proportions of superinfection and lack of efficacy cases (potential and adjudicated) were calculated overall and by study period. Results Off-label use (indication or age) decreased from 54.2% [95% confidence interval (95% CI): 49.0, 59.3%] pre-RMM to 35.7% (95% CI 30.4, 41.2%) post-RMM. Overall, 45.7% (95% CI 41.9, 49.5%) of patients were prescribed tigecycline off-label; the most commonly reported off-label indications were characterized as ''other'' (25.5%), hospital acquired pneumonia (8.2%), other pneumonia (6.3%), bacteremia (5.2%) and diabetic foot infection (1.5%). Across study periods, incidence proportions of definite or probable superinfection and lack of efficacy in adults treated for approved indications, authorized treatment doses and duration were 4.5% (95% CI 2.1, 8.4%) and 5.5% (95% CI 2.8, 9.7%), respectively. Conclusions Off-label use of tigecycline decreased following RMM implementation. Overall incidence proportions of definite or probable superinfection and lack of efficacy were low. EU PAS register number: EUPAS3674 Key PointsThe proportion of off-label tigecycline use decreased across five EU countries following implementation of a healthcare provider educational program Proportions of definite and probable superinfection and lack of efficacy were low across both study periods & Vera Frajzyngier

Evaluation of the Effectiveness of Additional Risk Minimization Measures for Voriconazole in the EU: Findings and Lessons Learned from a Healthcare Professional Survey

“…Of note, risk minimization measures have previously been shown to be effective. They were introduced to reduce the off-label use of tigecycline, and a retrospective study of their effectiveness concluded that this did decrease following implementation [44].…”

Safety and Efficacy of Tigecycline to Treat Multidrug-resistant Infections in Pediatrics: An Evidence Synthesis

“…The Tigecycline Post-Authorization Safety Study (PASS) was an observational cohort study that employed retrospective chart abstraction study design in which pre-recorded patient-centred data were reviewed (EU registration number EUPAS3674). 14 The study enrolled 777 patients from 13 sites in 5 EU countries (2 sites in Austria, 4 in Germany, 3 in Italy, 2 in Greece, 2 in the UK). The study primary objectives were: 1) to evaluate the effectiveness of risk minimisation measures (RMM) for tigecycline by describing prescription patterns among patients treated with any dose of tigecycline for any indication (on-or off-label) in the EU before and following implementation of RMM, and 2) to determine the incidence of superinfection and lack of efficacy among adult patients treated with approved doses of tigecycline for cIAI and cSSTI in the EU prior to and after implementation of RMM.…”