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Study Design Study Results Safety Dosing NCCN Guidelines®

Metastatic Dosing
Metastatic Dosing

Dosing with NERLYNX + capecitabine

NERLYNX + CAPECITABINE IS ADMINISTERED ORALLY IN A 21-DAY DOSING CYCLE3,*

  • Instruct patients to take capecitabine with water within 30 minutes after a meal on days 1 to 14 of each 21-day cycle21,†

  • If a patient misses a dose, do not replace missed dose, and instruct the patient to resume NERLYNX with the next scheduled daily dose

  • 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
  • Recommended dose of NERLYNX is 240 mg once daily
  • Recommended dose of capecitabine is 1500 mg/m2 (750 mg/m2 BID)
*Administer loperamide starting with the first dose of NERLYNX: 4 mg TID on days 1-14; 4 mg BID on days 15-56; then 4 mg PRN (not to exceed 16 mg per day).
†When NERLYNX is used in combination with capecitabine, refer to the capecitabine Prescribing Information for dose modifications of capecitabine.
BID: twice daily; PRN: as needed; TID: three times daily.

Simple dose reductions to help manage side effects3

NERLYNX DOSE MODIFICATIONS OPTIONS3

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  • 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.
Proactive management, including antidiarrheal medications, and dietary changes may help patients remain on therapy3,22
Supportive Care Voucher Program
  • Up to 3 months’ free supply per antidiarrheal product
  • Available to all patients

  • Used at the dispensing pharmacy, with prescription(s) at local retail pharmacy, or through Puma Specialty Pharmacy network

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

Severity of Diarrhea*

Dosing modification
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 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

Based on NCI CTCAE v5.0 grading.

*Grading per CTCAE v5.0. Dosing modification guidance per NERLYNX package insert.

†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.

‡Reduce dose of capecitabine to 550 mg/m2 twice daily. Since capecitabine is provided as 150 mg or 500 mg tablets, it is recommended that the capecitabine dose reduction(s) is rounded down to the nearest 500 mg or multiple of 150 mg for the twice-daily dose. If the patient’s body surface area is >2.0, the standard of care for the study center can be utilized for capecitabine mg/m2 dosing. When NERLYNX is used in combination with capecitabine, refer to the capecitabine US Prescribing Information for dose modifications of capecitabine.

§Reduce capecitabine if NERLYNX was previously reduced or reduce NERLYNX if capecitabine was previously reduced.

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

ADL: activites of daily living; NCI CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

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 AST, 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

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

†Grading per CTCAE v5.0. Dosing modification guidance per NERLYNX package insert.

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

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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.

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Reference:

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  3. NERLYNX [package insert]. Los Angeles, CA: Puma Biotechnology, Inc.
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