Neratinib

Other name

-

International/Other brands

Nerlynx

Groups

Approved

Structure

Prescription products

Target

EGFR

Description

Neratinib was approved in July 2017 for use as an extended adjuvant therapy in Human Epidermal Growth Factor Receptor 2 (HER2) positive breast cancer. Approval was granted to Puma Biotechnology Inc. for the tradename Nerlynx. Neratinib is currently under investigation for use in many other forms of cancer.

Indications

Breast Cancer

Other indications

-

Mechaism of action

-

Absorption

Neratinib and its major active metabolites M3. M6, and M7 have a Tmax of 2-8 h [FDA Label]. Administration with a high fat meal increases Cmax by 1.7-fold and total exposure by 2.2-fold. Administration with a standard meal increases Cmax by 1.2-fold and total exposure by 1.1-fold. Administration with gastric acid reducing agents such as proton pump inhibitors reduces Cmax by 71% and total exposure by 65%.

Metabolism

Neratinib is mainly undergoes metabolism via CYP3A4 [FDA Label]. It is also metabolized by flavin-containing monooxygenase to a lesser extent. The systemic exposures of neratinib's active metabolites M3, M6, M7, and M11 are 15%, 33%, 22%, and 4%.

Toxicity

Use of neratinib may produce diarrhea and hepatotoxicity as clinically significant adverse effects [FDA Label]. Serious adverse reactions in the neratinib arm of the clinical trials included diarrhea (1.6%), vomiting (0.9%), dehydration (0.6%), cellulitis (0.4%), renal failure (0.4%), erysipelas (0.4%), alanine aminotransferase increase (0.3%), aspartate aminotransferase increase (0.3%), nausea (0.3%), fatigue (0.2%), and abdominal pain (0.2%).