NMEs with RI-related labeling impact

AUC and Cmax ratios presented were calculated by the University of Washington Drug Interaction Database Editorial Team using mean AUC and Cmax values available in the NDA review documents and may differ from those presented in the product label.

Drug NameRatioLabeling ImpactReference
Maximal AUCCmaxa
AUC ≥ 1.25b
 Avibactam19.55 (ESRD)1.40 (ESRD)Reduce dose (moderate, severe and ESRD)FDA (2015d)
 Sugammadex17.24 (severe to ESRD)Not ProvidedNot recommended (severe)FDA (2015e)
 Tenofovir alafenamide fumarate1.92 (severe); tenofovir: 6.05 (severe)1.83 (severe); tenofovir: 2.78 (severe)Not recommended (severe)FDA (2015m)
 Edoxaban1.93 (ESRD); metabolite M4: 4.5 (ESRD)0.93 (ESRD); metabolite M4: 2.0 (ESRD)Reduce dose (15–50 ml/min); not recommended (CrCL < 15 ml/min)FDA (2015w)
 Sacubitril1.30 (severe); LBQ657: 2.7 (severe)N/PReduce dose (severe)FDA (2015k)
 Lesinurad2.13 (severe)1.14 (severe)Contraindication (severe and ESRD)FDA (2015zg)
 Brexpiprazole1.85 (severe)1.00 (severe)Reduce dose (moderate, severe and ESRD)FDA (2015v)
 Lenvatinib1.66 (severe)0.95 (severe)Reduce dose (severe)FDA (2015q)
 Ixazomib citrate1.41 (severe)1.76 (severe)Reduce dose (severe and ESRD)FDA (2015s)
AUC ratio < 1.25b
No dedicated RI studyb
 LumacaftorN/TN/TExercise caution (severe and ESRD)FDA (2015u)
 CariprazineN/TN/TNot recommended (severe)FDA (2015zd)
 Tipiracil1.65 (moderate; population PK)N/TAdjust dose (moderate)FDA (2015r)
 Cholic acidcN/TN/TThe urinary excretion of atypical bile acids maybe reduced in renal impaired patients.FDA (2015f)
PMR Requested
 EluxadolineN/TN/TFDA (2015zc)
  • CrCL, creatinine clearance; ESRD, end stage renal disease; N/P, not provided; N/T, not tested.

  • a The Cmax ratios presented are for the same patient population as the maximal AUC ratio.

  • b With dosing recommendation.

  • c Labeling recommendations are extracted from clinical pharmacology and biopharmaceutics reviews.