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Convenient once-daily, oral dosing with NERLYNX

The recommended daily dose of NERLYNX is six 40-mg tablets (240 mg total), taken continuously for 1 year3

Take NERLYNX at approximately the same time every day, preferably at mealtime

If a dose is missed or vomited, do not replace smissed dose, resume NERLYNX the next day

NERLYNX tablets should be swallowed whole (tablets should not be chewed, crushed, or split prior to swallowing)

Avoid grapefruit in any form

Dosing and Administration Guide 

Dose escalation may be used as a diarrhea management and prevention strategy in extended adjuvant23

Dose escalation regimen evaluated in the CONTROL study23

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  • 3.3% (2/60) of patients in the NERLYNX dose escalation arm discontinued treatment due to diarrhea in the first month. No patients in the NERLYNX dose escalation arm discontinued treatment due to diarrhea after the first month23,*
  • CONTROL is a phase 2, open-label, nonrandomized, multicenter, multinational study to evaluate the effects of dose escalation or antidiarrheal prophylaxis on side effects with NERLYNX23,*

PRN: as needed.

*Data for the neratinib dose-escalation cohort included here are not yet complete.

Diarrhea generally occurs early and is of short duration

Control Study: treatment discontinuations due to diarrhea23,‡

GRADE 3 DIARRHEA RATES23

Cumulative median duration of Grade 3 diarrhea is 2 days; no Grade 4 diarrhea was reported in any cohort.

As of August 26, 2019, study treatment had been completed or discontinued by 100% of patients in all cohorts except for the NERLYNX dose escalation cohort (38%).

Supportive Care
Voucher Program§

  • Up to 3 months’ free supply per antidiarrheal product
  • For patients with commercial insurance coverage only
  • Used at the dispensing pharmacy, with prescription(s) at local retail pharmacy, or through Puma Specialty Pharmacy network

§Not valid for prescriptions purchased under Medicaid, Medicare, TRICARE, or similar federal or state programs or for patients who are Medicare eligible and enrolled in an employer-sponsored group waiver health plan or government-subsidized prescription drug benefit program for retirees.

Proactive management, including antidiarrheal medications, and dietary changes may help patients remain on therapy3,23

Simple dose reductions to help manage side effects3

NERLYNX dose modifications options3

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  • Patients who experienced dose holds and reductions maintained efficacy24

  • NERLYNX dose modifications are recommended based on individual safety and tolerability; adjust the dose as clinically indicated3

  • Some adverse reactions may require dose interruption, reduction, or discontinuation3,*

*Discontinue NERLYNX for patients who fail to recover to Grade 0-1 from treatment-related toxicity, for toxicities that result in a treatment delay >3 weeks, or for patients that are unable to tolerate 120 mg daily.

Management of diarrhea requires antidiarrheals, dietary changes, supportive care, and appropriate dose modifications3

Severity of diarrhea*

NCI CTCAE grading for diarrhea25

Perform stool cultures as clinically indicated to exclude infectious causes of Grade 3 or 4 diarrhea of any grade with complicated features3,†

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; hospitalization indicated; severe increase in ostomy output compared to baseline; limiting self-care ADL
Grade 4
Life-threatening consequences; urgent intervention indicated

Practical application

Hypothetical patient case (extended adjuvant)

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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 v4.0.

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.

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 or AST
(>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 or AST
(>20×ULN)
OR
Grade 4 bilirubin
(>10×ULN)
  • Discontinue NERLYNX permanently
  • Evaluate alternative causes

ALT: alanine aminotransferase; AST: aspartate aminotrasferase; IV: intravenous; ULN: upper limit of normal.

*Also refer to the diarrhea and hepatotoxicity dose modifications on this page.

Per NCI CTCAE v4.0.

View patient access and support

Select IMPORTANT SAFETY INFORMATION

Diarrhea: Aggressively manage diarrhea. If diarrhea occurs despite recommended prophylaxis, treat with additional anti-diarrheals, fluids, and electrolytes as clinically indicated. Withhold NERLYNX in patients experiencing severe and/or persistent diarrhea. Permanently discontinue NERLYNX in patients experiencing Grade 4 diarrhea or Grade ≥2 diarrhea that occurs after maximal dose reduction.

Please see additional IMPORTANT SAFETY INFORMATION below.

IMPORTANT SAFETY INFORMATION

NERLYNX® (neratinib) tablets, for oral use

INDICATIONS AND USAGE: NERLYNX is a kinase inhibitor indicated:

CONTRAINDICATIONS: None

WARNINGS AND PRECAUTIONS:

ADVERSE REACTIONS: The most common adverse reactions (reported in ≥5% of patients) were:

To report SUSPECTED ADVERSE REACTIONS, contact Puma Biotechnology, Inc. at 1-844-NERLYNX (1-844-637-5969) 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.