Long-term safety study of colistimethate sodium (Colobreathe®): Findings from the UK Cystic Fibrosis Registry

Published:August 14, 2020DOI:


      • Colistimethate sodium dry powder for inhalation (CMS-DPI) and comparator cohorts generally had similar rates of adverse events.
      • This study supports the long-term safety profile of CMS-DPI in people with cystic fibrosis (CF).
      • UK CF Registry data are suitable for long-term drug safety studies.



      As part of the risk management plan in Europe, a long-term observational study was conducted to monitor the safety of colistimethate sodium dry powder for inhalation (CMS-DPI) compared to other inhaled antibiotics.


      A cohort of CMS-DPI patients and a matched cohort were identified from the UK Cystic Fibrosis Registry (UKCFR) from 2014-2018. The primary outcome was a composite endpoint, defined as adverse events (AEs) or new cystic fibrosis (CF) complications. Other outcomes included pulmonary exacerbations and treatment discontinuations.


      Of 1466 and 3503 patients in the CMS-DPI and comparator cohorts, respectively, 82.7% and 79.4% had AEs. Among the most common new CF complications were osteopenia, CF-related diabetes, and increased liver enzymes. The adjusted event rate ratio (ERR) for the primary outcome was 1.25 (95% confidence interval [CI]: 1.18-1.33, p<0.001). After excluding new CF complications, there was no difference between cohorts (ERR=1.04, 95% CI: 0.79-1.38, p=0.785). Pulmonary exacerbations were common in CMS-DPI and comparator cohorts (78.0% and 79.9% of patients, respectively), with adjusted ERR of 1.02 (95% CI: 0.95-1.10, p=0.523). Rates of discontinuation were similar in the CMS-DPI and Tobramycin inhalation powder comparator cohorts (37.8% and 39.8% of patients, respectively).


      There was no difference in the rate of adverse events between CMS-DPI and comparator cohorts. The safety profile of CMS-DPI is similar to those of other inhaled antibiotics, supporting its long-term safety in people with CF. The UKCFR has developed a successful model for partnership with industry to conduct long-term studies aimed at assessing drug safety.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Journal of Cystic Fibrosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


      1. Cystic Fibrosis Foundation Patient Registry. 2017 Annual Data Report. 2018. Accessed 2 February 2020.

        • Flume P.A.
        • Van Devanter D.R.
        State of progress in treating cystic fibrosis respiratory disease.
        BMC Med. 2012; 10: 88
        • Flume P.A.
        • Mogayzel Jr., P.J.
        • Robinson K.A.
        • Goss C.H.
        • Rosenblatt R.L.
        • Kuhn R.J.
        • et al.
        Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations.
        Am J Respir Crit Care Med. 2009; 180: 802-808
        • Döring G.
        • Flume P.
        • Heijerman H.
        • Elborn J.S.
        Treatment of lung infection in patients with cystic fibrosis: current and future strategies.
        J Cyst Fibros. 2012; 11: 461-479
      2. Teva Pharmaceuticals Europe BV. Colobreathe: Summary of product characteristics. 2018. Accessed 2 February 2020.

        • Conole D.
        • Keating G.M.
        Colistimethate sodium dry powder for inhalation: a review of its use in the treatment of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis.
        Drugs. 2014; 74: 377-387
        • Agent P.
        • Parrott H.
        Inhaled therapy in cystic fibrosis: agents, devices and regimens.
        Breathe (Sheff). 2015; 11: 110-118
      3. European Medicines Agency. Colistimethate sodium - assessment report. 2011. Accessed 17 June 2019.

        • Kaplan S.
        • Patino O.
        • Rainville C.
        • Madison T.
        Assessment of colistimethate sodium (Colobreathe) risk minimization measures implemented in the European Union: a cross‐sectional study.
        Pharmacoepidemiol Drug Saf. 2020; 29: 219-223
      4. European Medicine Agency (EMA). Patient registries. Accessed 28 June 2020.

      5. European Medicine Agency (EMA). Initiative for patient registries: strategy and pilot phase. 2015. Accessed 28 June 2020.

        • Taylor-Robinson D.
        • Archangelidi O.
        • Carr S.B.
        • Cosgriff R.
        • Gunn E.
        • Keogh R.H.
        • et al.
        Data resource profile: the UK Cystic Fibrosis Registry.
        Int J Epidemiol. 2018; 47: 9-10e
      6. UK Cystic Fibrosis Registry. Annual data report 2018. August 2019. Accessed 20 January 2020.

        • Bilton D.
        • Caine N.
        • Cunningham S.
        • Simmonds N.J.
        • Cosgriff R.
        • Carr S.B.
        Use of a rare disease patient registry in long-term post-authorisation drug studies: a model for collaboration with industry.
        Lancet Respir Med. 2018; 6: 495-496
        • Austin P.C.
        An introduction to propensity score methods for reducing the effects of confounding in observational studies.
        Multivar Behav Res. 2011; 46: 399-424
        • Austin P.C.
        Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples.
        Stat Med. 2009; 28: 3083-3107
        • Castellani C.
        • Duff A.J.A.
        • Bell S.C.
        • Heijerman H.G.M.
        • Munck A.
        • Ratjen F.
        • et al.
        ECFS best practice guidelines: the 2018 revision.
        J Cyst Fibros. 2018; 17: 153-178
        • Flume P.A.
        • Clancy J.P.
        • Retsch-Bogart G.Z.
        • Tullis D.E.
        • Bresnik M.
        • Derchak P.A.
        • et al.
        Continuous alternating inhaled antibiotics for chronic pseudomonal infection in cystic fibrosis.
        J Cyst Fibros. 2016; 15: 809-815
        • Schuster A.
        • Haliburn C.
        • Döring G.
        • Goldman M.H.
        • Freedom Study Group
        Safety, efficacy and convenience of colistimethate sodium dry powder for inhalation (Colobreathe DPI) in patients with cystic fibrosis: a randomised study.
        Thorax. 2013; 68: 344-350
        • Konstan M.W.
        • Flume P.A.
        • Kappler M.
        • Chiron R.
        • Higgins M.
        • Brockhaus F.
        • et al.
        Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: the EAGER trial.
        J Cyst Fibros. 2011; 10: 54-61
        • Gunn E.
        • Caine N.
        • Cosgriff R.
        • Charman S.C.
        • Carr S.B.
        P082 UK Cystic Fibrosis Registry data validation programme.
        J Cyst Fibros. 2019; 18: S80-SS1
        • Volkova N.
        • Moy K.
        • Evans J.
        • Campbell D.
        • Tian S.
        • Simard C.
        • et al.
        Disease progression in patients with cystic fibrosis treated with ivacaftor: data from national US and UK registries.
        J Cyst Fibros. 2020; 19: 68-79