Concerns regarding exposure-response relationship for safety evaluation
Exposure-response analysis is also a focus of FDA and EMA concerns for safety evaluation. All antimicrobial agents should be evaluated for their safety profile in general and special populations by analyzing the correlation between dose/exposure and the safety endpoints and adverse reactions defined in clinical trials. In the example of ceftaroline fosamil, QT interval prolongation was considered as a safety endpoint in the exposure-response analysis [36]. One more example, voriconazole is metabolized by cytochrome P450 isozymes CYP2C19, CYP2C9 and CYP3A4 and these P450 isozymes are inhibited by voriconazole. So, if patients use the inhibitors or inducers of these isozymes, voriconazole should be prescribed cautiously, especially in the patients receiving concomitant treatment which are associated QT prolongation [37].