Inconsistent labeling of food effect for oral agents across therapeutic areas: differences between oncology and non-oncology products

Abstract

Purpose: Several recent oral oncology drugs were labeled for administration in fasted states despite the fact that food increases their bioavailability. Because this was inconsistent with the principles of oral drug delivery, we hypothesized that there were inconsistencies across therapeutic areas.

Experimental design: Oral agents approved by the U.S. Food and Drug Administration from January 2000 to May 2009 were included in our study. Comparison of the food labeling patterns between oncology and non-oncology drugs was made using Fisher's exact test.

Results: Of the 99 drugs evaluated, 34 showed significant food effects on bioavailability. When food markedly enhanced bioavailability, eight out of nine non-oncology drugs were labeled "fed" to take advantage of the food-drug interaction, whereas all oncology drugs (n = 3) were labeled to be administered in "fasted" states (Fisher's exact test, P = 0.01).

Conclusions: Drug labeling patterns with respect to food-drug interactions observed with oncology drugs are in contradiction with fundamental pharmacologic principles, as exemplified in the labeling of non-oncology drugs. .

FIGURE 1. Application of marked food effects on labels: Oncology VS Non-oncology

Food recommendations on 18 drugs with marked food effects (AUC ratio ≥1.5 or ≤0.5). Y-axis represents change of AUC from fasted states to fed states. Food recommendations in labels were to be administered with meals (fed), without meals (fasted), or without regards to meals (either). When food recommendation was made either fed or fasted on drugs with marked increase of AUC, oncology drugs were labeled as fed while most non-oncology drugs were labeled fed. (p=0.01, fisher exact test)

FIGURE 2. Relationship between food effects on bioavailability and inter-individual variation of drug exposure

Y-axis represents change in coefficient of variance of AUC from fasted to fed states. X-axis represents food effect on mean AUC. Examination of 23 drugs with significant food effects (AUC ratio ≥1.25 or ≤0.8) and available coefficient of variation (CV) data revealed inverse relationship between change in BA and change in IIV of drug exposure from prandial states.