Strength of evidence for labeled dosing recommendations in renal impairment.

BACKGROUND/AIMS: Renally excreted medications often require dose adjustment in patients with kidney impairment. While drug development and approval in the United States are typically based on several Phase I and II studies and one or more larger Phase III randomized trials, the basis for labeled dosing recommendations for patients with renal impairment is less well known. In response, we aimed to quantify the level of evidence used to recommend labeled dosing adjustments for newly approved drugs in patients with renal impairment. METHODS: We reviewed publicly available drug labels and approval packages for new molecular entities approved in the United States between 2012 and 2014. The sample was restricted to 29 renally excreted new molecular entities that were not granted orphan drug status. We extracted data regarding approved indications, normal dosing, dosing adjustments for patients with mild (estimated glomerular filtration rate >60 mL/min/1.73 m2), moderate (estimated glomerular filtration rate 30-<60 mL/min/1.73 m2), and severe (estimated glomerular filtration rate <30 mL/min/1.73 m2) renal impairment, characteristics of studies used to justify dosing adjustments, and numbers of subjects in each study. RESULTS: In all, 14 of 29 (48%) new molecular entities had labels that recommended dosing adjustments for patients with mild, moderate, and/or severe renal impairment. Among these 14 new molecular entities, 4 (29%) used only pharmacokinetic studies to justify the recommendations, with no examination of clinical outcomes for patients with renal impairment. Where data were available, the median number of patients with renal impairment evaluated in studies used for dosing adjustment was 34 (range, 4-5976). Of the 15 new molecular entities with no recommended dosing adjustments for this population, 2 (13%) did not report assessing the effects of renal impairment. CONCLUSION: Nearly half of newly approved renally excreted drugs include dosing adjustments for kidney impairment on the label, but the recommendations are usually based on very small numbers of patients and often utilize pharmacokinetic studies alone. More research is needed to understand the benefits and risks of new drugs in patients with renal impairment.