Neratinib (Nerlynx)
(Puma Biotechnology) High fat meal increases Cmax by 1.7-fold and increases total exposure by 2.2-fold; standard meal increases Cmax by 1.2-fold, increases total exposure by 1.1-fold; proton pump inhibitors decrease Cmax by 71% and decrease total exposure by 65%;
neratinib/metabolites have a Tmax=2-8 h;
Vd= 6433 L Metabolized mainly by CYP3A4 240 mg orally once daily;
>99% binding (AAG, HSA) In a Phase III study, neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET), interstitial lung disease occurred in two patients in the neratinib group and one patient in the placebo group, pulmonary fibrosis in one and two patients, respectively, and pneumonitis in one patient in each group (224)