• Extended adjuvant treatment of early stage human epidermal receptor type 2 (HER2)-overexpressed/amplified breast cancer following adjuvant trastuzumab-based therapy.
• Advanced or metastatic HER2-positive breast cancer in patients who have received 2 prior anti-HER2–based regimens in the metastatic setting (in combination with capecitabine).

Contraindicated in:

• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe hepatic impairment (↓ dose)
• Rep: Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: ↑risk of adverse reactions/side effects in older adults.

CV: hypotension.

Derm: rash, dry skin, nail disorder.

EENT: epistaxis.

GI: ↓appetite, abdominal pain, diarrhea, dyspepsia, nausea, stomatitis, vomiting, ↓ weight, abdominal distention, dry mouth, HEPATOTOXICITY.

GU: renal failure, urinary tract infection.

MS: muscle spasms.

Neuro: fatigue.

Drug-Drug:

• ↓levels with proton pump inhibitors, H₂ blockers, and antacids; avoid concurrent use with proton pump inhibitors; take 2 hr before next dose of H₂ antagonist or 10 hr after the H₂ antagonist; take 3 hr after antacids.
• Strong or moderate CYP3A4 inhibitors, including aprepitant, cimetidine, ciprofloxacin, clarithromycin, clotrimazole, cobicistat, conivaptan, crizotinib, cyclosporine, diltiazem, dronedarone, erythromycin, fluconazole, fluvoxamine, idelalisib, imatinib, itraconazole, ketoconazole, lopinavir, nefazodone, nelfinavir, posaconazole, ritonavir, tipranavir, verapamil, and voriconazole, may ↑ levels and risk of toxicity; avoid concurrent use.
• Strong or moderate CYP3A4 inducers, including bosentan, carbamazepine, efavirenz, enzalutamide, mitotane, modafanil, phenytoin, and rifampin, may ↓ levels and effectiveness; avoid concurrent use.
• May ↑ levels and risk of toxicity of digoxin.

Drug-Natural Products:

• St. John's wort may ↓ levels and effectiveness; avoid concurrent use.

• Tablets: 40 mg;

Extended Adjuvant Treatment of Early Stage Breast Cancer

• PO (Adults): Non-dose escalation strategy (administer antidiarrheal prophylaxis for the first 56 days of treatment on scheduled basis): 240 mg once daily until disease recurrence or for up to 1 yr OR Dose escalation strategy (use antidiarrheals only as needed for diarrhea): 120 mg once daily for 7 days, then 160 mg once daily for 7 days, then 240 mg once daily thereafter until disease recurrence or for up to 1 yr.

Advanced or Metastatic Breast Cancer

• PO (Adults): Non-dose escalation strategy (administer antidiarrheal prophylaxis for the first 56 days of treatment on scheduled basis): 240 mg once daily on days 1–21 of a 21-day cycle; continue until disease recurrence or unacceptable toxicity. OR Dose escalation strategy (use antidiarrheals only as needed for diarrhea): 120 mg once daily for 7 days, then 160 mg once daily for 7 days, then 240 mg once daily for 7 days, then 240 mg once daily on days 1–21 of a 21-day cycle; continue until disease recurrence of unacceptable toxicity.

Nerlynx

• Irreversibly binds to epidermal growth factor receptor (EGFR), HER2, and HER4 to inhibit growth of tumors that express HER2 and EGFR.

• Decreased progression of breast cancer and improved survival.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors, kinase inhibitors

Absorption: Blood levels ↑ by high-fat foods.

Distribution: Extensively distributed to tissues.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized in liver via the CYP3A4 isoenzyme into active metabolites (M3, M6, M7, and M11); 97% excreted in feces, <2% excreted by kidneys.

Half-life: 7–17 hr.

(plasma concentrations)

• Instruct patient to take neratinib as directed. If dose is missed, omit and take next scheduled dose next day. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
• Advise patient to avoid taking grapefruit or grapefruit juice during therapy.
• Instruct patient to take loperamide according to schedule and titrate to 1–2 bowel movements/day: For days 1–14 (wk 1–2), take 4 mg three times daily. Days 15–56 (wk 3–8), take 4 mg twice daily. Days 57–365 (wk 9–52), take 4 mg as needed up to 16 mg/day. May require additional antidiarrheal agents and dose reduction.
• Caution patient to avoid proton pump inhibitors and H₂ antagonists during therapy and to avoid taking antacids within 3 hr of neratinib.
• Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
• Advise patient to notify health care professional immediately if severe ( Grade 3) diarrhea or diarrhea associated with weakness, dizziness, or fever, or if signs and symptoms of liver dysfunction occur.
• Rep: May cause fetal harm. Advise females of reproductive potential to use effective contraception and avoid breastfeeding during and for at least 1 mo after last dose. Advise male patients with partners of reproductive potential to use effective contraception during and for 3 mo after last dose.

ne-RA-ti-nib

NDC Code^*

• 70437- Puma Biotechnology, Inc.
  • 70437-240- Nerlynx
    • 70437-240-18- 1 BOTTLE in 1 BOX (70437-240-18) > 180 TABLET in 1 BOTTLE

• 70437- Puma Biotechnology, Inc.
  • 70437-240- Nerlynx
    • 70437-240-26- 1 BOTTLE in 1 BOX (70437-240-26) > 126 TABLET in 1 BOTTLE