Indications for NERLYNX:
Extended adjuvant treatment of early stage HER2+ breast cancer following adjuvant trastuzumab-based therapy, as a single agent. Advanced or metastatic HER2+ breast cancer in adults who have received ≥2 prior anti-HER2 based regimens in the metastatic setting, in combination with capecitabine.
Initiate antidiarrheal prophylaxis (loperamide) with the first dose and continue during the first 2 treatment cycles (56 days); after Day 56, titrate to achieve 1–2 bowel movements per day; see full labeling. Swallow whole. Take with food. Early stage: 240mg once daily until disease recurrence or for up to 1 year. Dose modifications for adverse reactions: First dose reduction: 200mg/day; Second dose reduction: 160mg/day; Third dose reduction: 120mg/day; discontinue if unable to tolerate 120mg/day. Advanced or metastatic: 240mg once daily on Days 1–21 of a 21-day cycle with capecitabine (750mg/m2 twice daily) on Days 1–14 of a 21-day cycle until disease progression or unacceptable toxicity. Dose modifications for adverse reactions: First dose reduction: 160mg/day; Second dose reduction: 120mg/day. For both: Severe hepatic impairment (Child-Pugh C): reduce initial dose to 80mg. Dose modifications for diarrhea, hepatotoxicity, or general toxicities: see full labeling.
Monitor and treat diarrhea as needed; interrupt and reduce subsequent doses if severe diarrhea with dehydration occurs. Perform stool cultures as clinically indicated. Measure total bilirubin, AST/ALT, alkaline phosphatase prior to initiation, monthly for the first 3 months, then every 3 months during treatment and as clinically indicated. Severe hepatic impairment: reduce dose (see Adult dose). Embryo-fetal toxicity. Advise to use effective contraception during and for ≥1 month (females of reproductive potential) or 3 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for ≥1 month after the last dose).
Avoid concomitant PPIs, strong or moderate CYP3A4 inhibitors (eg, ketoconazole, fluconazole), other moderate CYP3A4 and P-gp dual inhibitors (eg, verapamil), strong or moderate CYP3A4 inducers (eg, rifampin), grapefruit products. Take ≥2hrs before or 10hrs after H2-receptor antagonists. Separate dosing by 3hrs after antacids. Increased cardiotoxicity risk with digoxin. May inhibit transport of P-gp substrates (eg, dabigatran, fexofenadine).
Diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST/ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, UTI; hepatotoxicity. In combination with capecitabine: also constipation, dizziness, back pain, arthralgia, upper RTI, renal impairment.
Generic Drug Availability: