Characterization of Dosing Recommendations for Renal Impairment Provided in Prescribing Information Since the FDA Guidance Document: Have the Recommendations Become More Clear?

Abstract

Objectives: To characterize the types of renal dosing recommendations provided in the prescribing information (aka package insert) before and after the FDA guidance for industry document regarding renal dosing, released in 1998. Methods: The prescribing information (PI) for all new molecular entities (NMEs) for three time periods was collected from the FDA website. Time period 1 was January 1995 to December 1997 and represents dosing recommendations prior to the FDA guidance statement. Time period 2 was January 2000 to December 2002 and time period 3 was January 2011 to December 2013. These represent recommendations after the FDA guidance statement. The renal dosing recommendations for each NME were reviewed and classified as either specific (includes CrCl, serum creatinine), nonspecific (mild, moderate, or severe impairment), caution, unnecessary, no information or other by two investigators independently. A further analysis was conducted for NMEs in time periods 1 and 2 with LexiComp and the most recent PIs located on FDA or company website. Presence of dialysis (hemodialysis or peritoneal) dosing recommendations was also recorded. Results: Time period 1 had significantly less NMEs characterized as No information in Lexicomp in comparison to original PIs (p= 0.02). A statistically significant decrease in original PIs characterized as Caution was observed between time periods 2 and 3 (p= .0004) and time periods 1 and 3 (p= 0.001). Conclusions: Terminology used in renal dosing recommendations in PIs does not seem to be clearer over the past years. There remains a need for improved quality of dosing information within PIs.