Neratinib
Indications
Neratinib is used for:
Breast Cancer
Adult Dose
Breast Cancer
Indicated for the extended adjuvant treatment of early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy
240 mg (6 tablets) PO qDay with food continuously for 1 yr
Hepatic impairment
Severe (Child-Pugh C): Reduce starting dose to 80 mg
Mild-moderate (Child-Pugh A or B): No dose modifications required
Child Dose
Renal Dose
Administration
Take with food at approximately the same time each day
Contra Indications
Precautions
Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated; withhold therapy in patients experiencing severe and/or persistent diarrhea; permanently discontinue in patients experiencing grade 4 diarrhea or grade ≥2 diarrhea that occurs after maximal dose reduction (see Dosage Modifications; loperamide may lower the incidence and severity of diarrhea (see Oral Administration)
No clinically relevant effect on the QTc intervals
Hepatoxicity reported with therapy; monitor liver function test at baseline, once monthly for the first 3 months, followed by q3 months while on treatment and as clinically indicated; discontinue and do not restart therapy if patients experience severe changes in liver function tests
Pregnancy-Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women; ; females of reproductive potential should have a pregnancy test prior to starting treatment
If drug used during pregnancy, or if patient becomes pregnant while taking drug, patient should be apprised of potential hazard to fetus
Animal studies
Administration to pregnant rabbits during organogenesis caused abortions, embryo-fetal death, and fetal abnormalities in rabbits at maternal AUCs approximately 0.2 times the AUC in patients receiving the recommended dose
Contraception
Females of reproductive potential should use effective contraception during treatment and for at least 1 month after last dose of drug
Males with females of reproductive potential should use effective contraception during treatment and for 3 months after the last dose
Lactation
Unknown if distributed in human breast milk
Because of the potential for serious adverse reactions in breastfed infants, advise lactating women not to breastfeed while taking neratinib and for at least 1 month after the last dose
Interactions
Neratinib is a CYP3A4 substrate and inhibits P-glycoprotein (P-gp) transporters CYP3A4 inducers (eg, rifampin, carbamazepine) decrease neratinib serum levels
Coadministration with strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin, grapefruit juice) may increase neratinib serum levels
Caution if using concomitant P-gp substrates; monitor substrate for necessary dosage adjustments
Adverse Effects
Side effects of Neratinib :
>10%
Diarrhea, all grades (95%)
Nausea (43%)
Diarrhea, grade 3 (40%)
Abdominal pain (36%)
Fatigue (27%)
Vomiting (26%)
Rash (18%)
Stomatitis (14%)
Decreased appetite (12%)
Muscle spasms (11%)
1-10%
Dyspepsia (10%)
Increased ALT (9%)
Nail disorder (8%)
Increased AST (7%)
Dry skin (6%)
Abdominal distension (5%)
Epistaxis (5%)
Urinary tract infection (5%)
Weight decreased (5%)
Dehydration (4%)
Dry mouth (3%)
Skin fissures (2%)
Mechanism of Action
Irreversible tyrosine kinase inhibitor (TKI) that blocks signal transduction through the epidermal growth factor receptors (EGFRs), human epidermal growth factor receptor 2 (HER2), and HER4
In vitro, inhibition reduces EGFR and HER2 autophosphorylation, subsequently inhibits signal transduction pathways, and demonstrates antitumor activity in overexpressed EGFR and/or HER2 carcinoma cells; neratinib human metabolites (M3, M6, M7, and M11) inhibit EGFR, HER2, and HER4 activity