Drug interactions of Neratinib

1. Effects of Other Drugs on Neratinib

Gastric Acid-Reducing Agents

Clinical Impact: Concomitant use of neratinib with proton pump inhibitors (PPIs), H2-receptor antagonists, or antacids may decrease the AUC of neratinib, which could reduce neratinib activity.

Prevention or Management: Avoid concomitant use with PPIs. Administer neratinib at least 2 hours before or at least 10 hours after administration of H2-receptor antagonists. Administer neratinib at least 3 hours after administration of antacids.

Strong CYP3A4 Inhibitors

Clinical Impact: Concomitant use of neratinib with strong CYP3A4 inhibitors increases the Cmax and AUC of neratinib, which may increase the risk of neratinib toxicity.

Prevention or Management: Avoid concomitant use of neratinib with strong CYP3A4 inhibitors.

Dual P-gp and Moderate CYP3A4 Inhibitors

Clinical Impact: Concomitant use of neratinib with dual P-gp and moderate CYP3A4 inhibitors may increase the Cmax and AUC of neratinib, which may increase the risk of neratinib toxicity.

Prevention or Management: Avoid concomitant use of neratinib with dual P-gp and moderate CYP3A4 inhibitors.

Strong or Moderate CYP3A4 Inducers

Clinical Impact: Concomitant use of neratinib with strong or moderate CYP3A4 inducers decreases the Cmax and AUC of neratinib, which could reduce neratinib activity.

Prevention or Management: Avoid concomitant use of neratinib with strong or moderate CYP3A4 inducers.

AUC = Area Under the Concentration-Time Curve; Cmax = Maximum Plasma Concentration

2. Effects of Neratinib on Other Drugs

Certain P-glycoprotein (P-gp) Substrates

Concomitant use of neratinib increases the concentrations of P-gp substrates, which may elevate the risk of adverse reactions associated with these substrates. Monitor for adverse reactions of certain P-gp substrates for which minimal concentration changes may lead to severe adverse reactions.

FDA，2021.06