NMEs with HI-related labeling impact

The 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
 Eluxadoline13.74 (severe)14.25 (severe)Reduce dose (mild and moderate); contraindication (severe)FDA (2015zc)
 Flibanserin4.53 (mild)0.91 (mild)Contraindication (any HI)FDA (2015a)
 Lenvatinib2.57 (severe)0.54 (severe)Reduce dose (severe)FDA (2015q)
 Isavuconazonium sulfateIsavuconazole: 2.19 (moderate)cIsavuconazole: 0.77 (moderate)cNot recommended (severe)FDA (2015i)
 Panobinostat2.05 (moderate)1.83 (moderate)Reduce dose (mild and moderate); avoid use (severe)FDA (2015l)
 Selexipag4 (moderate); ACT-333679: 2 (moderate)N/PAvoid use (severe)FDA (2015z)
 Sacubitril3.45 (moderate); LBQ657: 1.9 (moderate)N/PReduce dose (moderate); not recommended (severe)FDA (2015k)
 Lumacaftor1.50 (moderate)1.30 (moderate)Reduce dose (moderate and severe)FDA (2015u)
 Brexpiprazole1.46 (moderate)0.76 (moderate)Reduce dose (moderate and severe)FDA (2015v)
 Lesinurad1.33 (moderate)1.08 (moderate)Not recommended (severe)FDA (2015zg)
 Ixazomib citrateIxazomib: 1.27 (moderate)Ixazomib: 1.21 (moderate)Reduce dose (moderate, severe)FDA (2015s)
 Edoxaban0.95 (mild); metabolite M4: 1.25 (mild)0.9 (mild); metabolite M4: 1.1 (mild)Not recommended (moderate and severe)FDA (2015w)
AUC ratio < 1.25b
 Rolapitant1.04 (moderate)0.77 (moderate)Avoid use (severe)FDA (2015za)
 Cariprazine1.15 (moderate)1.14 (moderate)Not recommended (severe)FDA (2015zd)
 Tenofovir alafenamide fumarate0.92 (mild); tenofovir: 0.89 (mild)N/PNot recommended (severe)FDA (2015m)
No dedicated HI studyb
 IvabradineN/TN/TContraindication (severe)FDA (2015g)
PMR Requested
 PalbociclibN/TN/TFDA (2015n)
 TrabectedinN/TN/TFDA (2015zf)
 CobimetinibN/TN/TFDA (2015h)
 OsimertinibN/TN/TFDA (2015x)
 AlectinibN/TN/TFDA (2015b)
  • 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 Drug was given intravenously.