Summary of the safety and tolerability of two treatment regimens of ceftaroline fosamil: 600 mg every 8 h versus 600 mg every 12 h

Karen Cheng, Rienk Pypstra, Jean Li Yan, Jennifer Hammond, Karen Cheng, Rienk Pypstra, Jean Li Yan, Jennifer Hammond

Abstract

Background: The recommended adult dose of ceftaroline fosamil is 600 mg q12h by 1 h intravenous (iv) infusion for 5-14 days in complicated skin and soft tissue infection (cSSTI) and 5-7 days in community-acquired pneumonia (CAP). A dosage of 600 mg q8h by 2 h iv infusion is approved in some regions for cSSTI patients with Staphylococcus aureus infection where the ceftaroline MIC is 2 or 4 mg/L. This analysis compares the safety profiles of the q8h and q12h regimens.

Methods: Safety data from six Phase III, randomized, double-blind clinical trials were collated into the q8h cSSTI pool (ceftaroline fosamil n = 506; NCT01499277) and the q12h pool {ceftaroline fosamil n = 1686; comprising five studies [two cSSTI (NCT00424190 and NCT00423657) and three CAP (NCT01371838, NCT00621504 and NCT00509106)]}.

Results: The pattern and incidence of adverse events were similar between the q8h and q12h ceftaroline fosamil pools. Most were gastrointestinal and of mild or moderate intensity. Overall, rash intensity was similar between the q8h pool and the q12h pool. For the q8h regimen, there was a higher frequency of rash in some Asian study sites, associated with longer duration of therapy (≥7 days); most cases were mild and resolved following treatment discontinuation. No dose-related vital sign or ECG abnormalities were detected with either regimen.

Conclusions: The q8h regimen in cSSTI was generally well tolerated; the observed safety profile was consistent with the known safety profile of ceftaroline fosamil, reflective of the cephalosporin class and qualitatively consistent with the q12h regimen.

© The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.

References

    1. EMA. Zinforo (Ceftaroline Fosamil) Summary of Product Characteristics .
    1. Corey GR, Wilcox MH, Talbot GH. et al. CANVAS 1: the first Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother 2010; 65 Suppl 4: iv41–51.
    1. Wilcox MH, Corey GR, Talbot GH. et al. CANVAS 2: the second Phase III, randomized, double-blind study evaluating ceftaroline fosamil for the treatment of patients with complicated skin and skin structure infections. J Antimicrob Chemother 2010; 65 Suppl 4: iv53–65.
    1. Dryden M, Zhang Y, Wilson D. et al. A Phase III, randomized, controlled, non-inferiority trial of ceftaroline fosamil 600 mg every 8 h versus vancomycin plus aztreonam in patients with complicated skin and soft tissue infection with systemic inflammatory response or underlying comorbidities. J Antimicrob Chemother 2016; 71: 3575–84.
    1. Li J, Singh R, Ambler JE. Probability of target attainment (PTA) and pharmacokinetic/pharmacodynamic (PK/PD) breakpoint for ceftaroline fosamil 600 mg every 12 h and every 8 h against Staphylococcus aureus In: Abstracts of the Twenty-fifth European Congress of Clinical Microbiology and Infectious Diseases, Copenhagen, Denmark, 2015. Abstract P1384. ESCMID, Basel, Switzerland.
    1. Castanheira M, Jones RN, Sader HS.. Activity of ceftaroline and comparator agents tested against contemporary Gram-positive and -negative (2011) isolates collected in Europe, Turkey, and Israel. J Chemother 2014; 26: 202–10.
    1. Flamm RK, Sader HS, Farrell DJ. et al. Summary of ceftaroline activity against pathogens in the United States, 2010: report from the Assessing Worldwide Antimicrobial Resistance Evaluation (AWARE) surveillance program. Antimicrob Agents Chemother 2012; 56: 2933–40.
    1. Flamm RK, Sader HS, Jones RN.. Ceftaroline activity tested against contemporary Latin American bacterial pathogens (2011). Braz J Infect Dis 2014; 18: 187–95.
    1. Flamm RK, Jones RN, Sader HS.. In vitro activity of ceftaroline tested against isolates from the Asia-Pacific region and South Africa (2011). J Glob Antimicrob Resist 2014; 2: 183–9.
    1. Biedenbach DJ, Alm RA, Lahiri SD. et al. In vitro activity of ceftaroline against Staphylococcus aureus isolated in 2012 from Asia-Pacific countries as part of the AWARE surveillance program. Antimicrob Agents Chemother 2015; 60: 343–7.
    1. Alm RA, McLaughlin RE, Kos VN. et al. Analysis of Staphylococcus aureus clinical isolates with reduced susceptibility to ceftaroline: an epidemiological and structural perspective. J Antimicrob Chemother 2014; 69: 2065–75.
    1. File TM Jr, Low DE, Eckburg PB. et al. FOCUS 1: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother 2011; 66 Suppl 3: iii19–32.
    1. Low DE, File TM Jr, Eckburg PB. et al. FOCUS 2: a randomized, double-blinded, multicentre, Phase III trial of the efficacy and safety of ceftaroline fosamil versus ceftriaxone in community-acquired pneumonia. J Antimicrob Chemother 2011; 66 Suppl 3: iii33–44.
    1. Zhong NS, Sun T, Zhuo C. et al. Ceftaroline fosamil versus ceftriaxone for the treatment of Asian patients with community-acquired pneumonia: a randomised, controlled, double-blind, phase 3, non-inferiority with nested superiority trial. Lancet Infect Dis 2015; 15: 161–71.
    1. Guidance for Industry: Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment FDA, USA: Center for Drug Evaluation and Research. .
    1. Ioannidis JP, Evans SJ, Gotzsche PC. et al. Better reporting of harms in randomized trials: an extension of the CONSORT statement. Ann Intern Med 2004; 141: 781–8.
    1. Brayfield A. Martindale: The Complete Drug Reference. 39th edn London, UK: Pharmaceutical Press, 2017. .
    1. Athans V, Kenney RM, Wong J. et al. Outpatient use of ceftaroline fosamil versus vancomycin for osteoarticular infection: a matched cohort study. J Antimicrob Chemother 2016; 71: 3568–74.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere