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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 cycle27

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

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

  • Avoid grapefruit in any form

*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).
  • Recommended dose of NERLYNX is 240 mg once daily
  • Recommended dose of capecitabine is 1500 mg/m2 (750 mg/m2 BID)
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 therapy3,23
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.

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

Severity of Diarrhea*

Dosing modification
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

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.

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.

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

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.

Select IMPORTANT SAFETY INFORMATION

Drug interactions: 1. Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors. When patients require gastric acid reducing agents, use an H2-receptor antagonist or antacid. Separate NERLYNX by at least 3 hours with antacids. Separate NERLYNX by at least 2 hours before or 10 hours after H2-receptor antagonists. 2. Strong CYP3A4 inhibitors: Avoid concomitant use. 3. Moderate CYP3A4 and P-glycoprotein (P-gp) dual inhibitors: Avoid concomitant use. 4. Strong or moderate CYP3A4 inducers: Avoid concomitant use. 5. P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with NERLYNX.

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.