PT-021 - PHARMACOKINETIC (PK) BASIS OF STATIN DRUG-DRUG INTERACTION (DDI) INFORMATION IN FDA LABELS.

J. Mease, A. Ramamoorthy, X. Yang, R. Madabushi, E. Pfuma Fletcher, I. Zineh; US Food and Drug Administration, Silver Spring, MD, USA.

Background: Statins are widely prescribed and highly susceptible to PK-based DDIs. There has not been a comprehensive analysis of the consistency of PK-based statin DDI recommendations in prescription drug labeling. We conducted such an analysis to inform future FDA labeling practices.

Methods: We catalogued statin DDI information for new molecular entities (NMEs) approved from 2010 – 2021 using FDALabel. PK data (AUC, Cmax ratios) from statin DDI studies were also collected. Statin DDI management recommendations were grouped into 4 categories (Table 1) and compared with corresponding PK results to assess consistency in the PK-basis for the labeling recommendations.

Results: Information on 156 statin DDIs was found across 73 labels as follows: 35% “No Dose Adjustment,” 16% “Use Caution,” 35% “Dose Adjustment,” and 14% “Avoid Coadministration.” Recommendations were mapped to their corresponding PK changes in Table 1. The strength of the labeling recommendation generally corresponded with the magnitude of the DDI-mediated PK change.

Conclusion: Statin DDI labeling is generally related to the magnitude of the AUCR change from clinical DDI studies. Minor deviations to this trend were observed. An evaluation of whether these deviations were justified (e.g. availability of safety data) is warranted. Standardized labeling for statin DDI recommendations may be possible.

Table 1. Statin DDI Recommendations Mapped with PK Data (AUCR)