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

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