Dosing

Dose modifications for diarrhea

Management of diarrhea requires anti-diarrheals, dietary changes, supportive care, and appropriate dose modifications.1

Severity of diarrhea*

dose modifications chart_dose modifications chart

NCI CTCAE grading for diarrhea24

Perform stool cultures as clinically indicated to exclude infectious causes of Grade 3 or 4 diarrhea of any grade with complicated features1,‡

Grade 1

Increase of < 4 stools per day over baseline; mild increase in ostomy output compared to baseline

Grade 2

Increase of 4–6 stools per day over baseline; moderate increase in ostomy output compared to baseline; limiting instrumental ADL

Grade 3

Increase of ≥ 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self care ADL

Grade 4

Life-threatening consequences; urgent intervention indicated

Practical application of dose modifications

Hypothetical patient case A

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NCI CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading for diarrhea; ADL: activities of daily living

*Per CTCAE v4.03.

Institute the following: diet modifications, maintain ~2 L fluid intake per day, and once event resolves to ≤ Grade 1 or baseline, start loperamide 4 mg with each subsequent NERLYNX administration.

Complicated features include dehydration, fever, hypotension, renal failure, or Grade 3 or 4 neutropenia.

§Despite being treated with optimal medical therapy.


Dose modifications for other adverse events

Management of other adverse events associated with NERLYNX may require a dose interruption or treatment discontinuation.

General Toxicities||
TOXICITY SEVERITY* RECOMMENDED ACTION
GRADE 3 Hold NERLYNX until recovery to Grade ≤ 1 or baseline within 3 weeks of stopping treatment, then resume NERLYNX at the next lower dose level
GRADE 4 Discontinue NERLYNX permanently
Hepatic Impairment
  • Reduce NERLYNX starting dose to 80 mg in patients with severe hepatic impairment (Child Pugh C)

  • No dose modifications are recommended for patients with mild to moderate hepatic impairment
    (Child Pugh A or B)

Hepatotoxicity
  • Evaluate liver function tests in patients who experience ≥ Grade 3 diarrhea requiring IV fluid treatment
    or any signs or symptoms of hepatotoxicity

  • Collect fractionated bilirubin and prothrombin time during hepatotoxicity evaluation

 
HEPATOTOXICITY
SEVERITY*
RECOMMENDED ACTION

Grade 3 ALT (> 5–20× ULN)
OR
Grade 3 bilirubin (3–10× ULN)

  • Hold NERLYNX  until recovery to ≤ Grade 1

  • Evaluate alternative causes

  • Resume NERLYNX at the next lower dose level if recovery to ≤ Grade 1 occurs within 3 weeks.
    If Grade 3 ALT or bilirubin occurs again despite one dose reduction, permanently discontinue NERLYNX

Grade 4 ALT (> 20× ULN)
OR
Grade 4 bilirubin (> 10× ULN)

  • Discontinue NERLYNX permanently

  • Evaluate alternative causes

ALT: alanine aminotransferase; IV: intravenous; ULN: upper limit of normal

*Per CTCAE v4.03.

||Also refer to diarrhea and hepatotoxicity dose modifications in this guide.

PROACTIVE DIARRHEA MANAGEMENT

Adding budesonide to loperamide prophylaxis has been shown to lower the incidence, severity, and duration of diarrhea.3

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DOSING AND ADMINISTRATION GUIDE

View the full dosing and administration guide to learn more about dose modifications, anti-diarrheal prophylaxis, and drug interactions with NERLYNX.

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Learn about NERLYNX patient support

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early-stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (>5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) and www.NERLYNX.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS:

For Full Prescribing Information, please click here.