Nerlynx Side Effects Center

Last updated on RxList: 7/14/2022
Nerlynx Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Nerlynx?

Nerlynx (neratinib) tablets are 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.

What Are Side Effects of Nerlynx?

Common side effects of Nerlynx include:

Seek medical care or call 911 at once if you have the following serious side effects:

  • Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
  • Serious heart symptoms such as fast, irregular, or pounding heartbeats; fluttering in your chest; shortness of breath; and sudden dizziness, lightheartedness, or passing out;
  • Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, loss of coordination, feeling unsteady, very stiff muscles, high fever, profuse sweating, or tremors.

This document does not contain all possible side effects and others may occur. Check with your physician for additional information about side effects.

Dosage for Nerlynx

Initiate loperamide with the first dose of Nerlynx and continue during first 2 cycles (56 days) of treatment. Patients are instructed to maintain 1-2 bowel movements per day and on how to use antidiarrheal treatment regimens. The recommended dose of Nerlynx is 240 mg (6 tablets) given orally once daily with food, continuously for one year.

What Drugs, Substances, or Supplements Interact with Nerlynx?

Nerlynx may interact with proton pump inhibitors (PPIs), H2-receptor antagonists, antacids, macrolide antibiotics, cobicistat, conivaptan, antivirals, diltiazem, grapefruit juice, idelalisib, azole antifungals, nefazodone, carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, bosentan, efavirenz, etravirine, modafinil, digoxin, dabigatran, and fexofenadine. Tell your doctor all medications and supplements you use.

Nerlynx During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Nerlynx; it is unknown how it may affect a fetus. It is unknown if Nerlynx passes into breast milk. Because of the potential for serious adverse reactions in breastfed infants from Nerlynx, breastfeeding is not recommended while taking Nerlynx and for at least 1 month after the last dose.

Additional Information

Our Nerlynx (neratinib) Tablets Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

QUESTION

A lump in the breast is almost always cancer. See Answer
Nerlynx Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

  • severe or ongoing diarrhea;
  • pain or burning when you urinate;
  • kidney problems--little or no urination, swelling in your feet or ankles, feeling tired or short of breath; or
  • liver problems--right-sided upper stomach pain, vomiting, tiredness, fever, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Your cancer treatments may be delayed or permanently discontinued if you have certain side effects.

Common side effects may include:

  • kidney problems;
  • abnormal liver function tests;
  • diarrhea, constipation;
  • painful urination;
  • nausea, vomiting, stomach pain, bloating;
  • upset stomach, loss of appetite;
  • dizziness, feeling weak or tired;
  • nosebleed;
  • rash, dry skin, problems with your fingernails or toenails;
  • dry mouth, mouth sores;
  • back pain, joint pain, muscle spasms;
  • weight loss; or
  • cold symptoms such as stuffy nose, sneezing, sore throat.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Nerlynx (Neratinib Tablets)

SLIDESHOW

Breast Cancer Awareness: Symptoms, Diagnosis, and Treatment See Slideshow
Nerlynx Professional Information

SIDE EFFECTS

The following clinically significant adverse reactions are described elsewhere in the labeling:

  • Diarrhea [see WARNINGS AND PRECAUTIONS]
  • Hepatotoxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Extended Adjuvant Treatment Of Early-Stage Breast Cancer

ExteNET

The data described below reflect the safety data of NERLYNX as a single agent in ExteNET, a multicenter, randomized, double-blind, placebo-controlled study of NERLYNX within 2 years after completion of adjuvant treatment with trastuzumab-based therapy in women with HER2-positive early-stage breast cancer. Patients who received NERLYNX in this trial were not required to receive any prophylaxis with antidiarrheal agents to prevent the NERLYNX-related diarrhea. Patients were treated with 240 mg of NERLYNX given orally once daily with food, continuously until disease recurrence or for up to one year. The median duration of treatment was 11.6 months in the NERLYNX arm and 11.8 months in the placebo arm. The median age was 52 years (60% were ≥50 years old, 12% were ≥65 years old); 81% were Caucasian, 3% Black or African American, 14% Asian, and 3% other. A total of 1408 patients were treated with NERLYNX.

NERLYNX dose reduction due to an adverse reaction of any grade occurred in 31% of patients receiving NERLYNX compared to 2.6% of patients receiving placebo. Permanent discontinuation due to any adverse reaction was reported in 28% of NERLYNX-treated patients. The most common adverse reaction leading to discontinuation was diarrhea, accounting for 17% of NERLYNX-treated patients.

The most common adverse reactions (≥5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increased, nail disorder, dry skin, abdominal distention, epistaxis, weight decreased, and urinary tract infection. The most frequently reported Grade 3 or 4 adverse reactions were diarrhea, vomiting, nausea, and abdominal pain.

Serious adverse reactions in the NERLYNX arm included diarrhea (1.6%), vomiting (0.9%), dehydration (0.6%), cellulitis (0.4%), renal failure (0.4%), erysipelas (0.4%), ALT increased (0.3%), AST increased (0.3%), nausea (0.3%), fatigue (0.2%), and abdominal pain (0.2%).

Table 7 summarizes the adverse reactions in ExteNET.

Table 7: Adverse Reactions Reported in ≥2% of NERLYNX-Treated Patients in ExteNET

System Organ Class (Preferred Term) NERLYNX
n=1408
Placebo
n=1408
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Gastrointestinal Disorders
Diarrhea 95 40 0.1 35 2 0
Nausea 43 2 0 22 0.1 0
Abdominal pain* 36 2 0 15 0.4 0
Vomiting 26 3 0 8 0.4 0
Stomatitis† 14 0.6 0 6 0.1 0
Dyspepsia 10 0.4 0 4 0 0
Abdominal distension 5 0.3 0 3 0 0
Dry mouth 3 0.1 0 2 0 0
General Disorders and Administration Site Conditions
Fatigue 27 2 0 20 0.4 0
Hepatobiliary Disorders
Alanine aminotransferase increased 9 1 0.2 3 0.2 0
Aspartate aminotransferase increased 7 0.5 0.2 3 0.3 0
Infections and Infestations
Urinary tract infection 5 0.1 0 2 0 0
Investigations
Weight decreased 5 0.1 0 0.5 0 0
Metabolism and NutritionDisorders
Decreased appetite 12 0.2 0 3 0 0
Dehydration 4 0.9 0.1 0.4 0.1 0
Musculoskeletal and Connective Tissue Disorders
Muscle spasms 11 0.1 0 3 0.1 0
Respiratory, Thoracic and Mediastinal Disorders
Epistaxis 5 0 0 1 0.1 0
Skin and Subcutaneous Tissue Disorders
Rash‡ 18 0.6 0 9 0 0
Dry skin 6 0 0 2 0 0
Nail disorder§ 8 0.3 0 2 0 0
Skin fissures 2 0.1 0 0.1 0 0
* Includes abdominal pain, abdominal pain upper, and abdominal pain lower
† Includes stomatitis, aphthous stomatitis, mouth ulceration, oral mucosal blistering, mucosal inflammation, oropharyngeal pain, oral pain, glossodynia, glossitis, and cheilitis
‡ Includes rash, rash erythematous, rash follicular, rash generalized, rash pruritic, rash pustular, rash maculo-papular, rash papular, dermatitis, dermatitis acneiform, and toxic skin eruption
§ Includes nail disorder, paronychia, onychoclasis, nail discoloration, nail toxicity, nail growth abnormal, and nail dystrophy

Advanced Or Metastatic Breast Cancer

NALA

The data described below reflect the safety data of NERLYNX plus capecitabine in NALA, a randomized, multicenter, multinational, open-label, active-controlled study of HER2-positive metastatic breast cancer in patients, with or without brain metastases, who have received two or more prior anti HER2-based regimens in the metastatic setting.

Patients were treated with NERLYNX 240 mg orally once daily Days 1-21 of a 21-day cycle in combination with capecitabine (750 mg/m² given orally twice daily) Days 1-14 of a 21-day cycle, or lapatinib 1250 mg orally once daily Days 1-21 of a 21-day cycle in combination with capecitabine (1000 mg/m² given orally twice daily) Days 1-14 of a 21-day cycle until disease progression. The median duration of treatment was 5.7 months in the NERLYNX plus capecitabine arm and 4.4 months in the lapatinib plus capecitabine arm.

NERLYNX dose reduction due to an adverse reaction of any grade occurred in 10% of patients receiving NERLYNX plus capecitabine. Permanent discontinuation due to any adverse reaction was reported in 14% of NERLYNX plus capecitabine treated patients. The most common adverse reactions leading to discontinuation were vomiting (3.6%), diarrhea (2.6%), nausea (2.6%), and palmar-plantar erythrodysaesthesia syndrome (2.3%) of NERLYNX plus capecitabine-treated patients.

The most common adverse reactions of any grade (≥5%) in the NERLYNX plus capecitabine arm were diarrhea, nausea, vomiting, decreased appetite, constipation, fatigue/asthenia, weight decreased, dizziness, back pain, arthralgia, urinary tract infection, upper respiratory tract infection, abdominal distention, renal impairment, and muscle spasms. The most frequently reported Grade 3 or 4 adverse reactions were diarrhea, nausea, vomiting, fatigue, and decreased appetite.

Serious adverse reactions ≥2% in the NERLYNX plus capecitabine arm included diarrhea (7%), vomiting (3%), nausea (2.3%), and acute kidney injury (2.3%).

Table 8 summarizes the adverse reactions in NALA.

Table 8: Adverse Reactions Reported in ≥2% of NERLYNX-Treated Patients in Combination with Capecitabine in NALA

System Organ Class (Preferred Term) NERLYNX + Capecitabine
n=303
Lapatinib + Capecitabine
n=311
All Grades (%) Grade 3 (%) Grade 4 (%) All Grades (%) Grade 3 (%) Grade 4 (%)
Gastrointestinal Disorders
Diarrhea 83 25 0 66 13 0
Nausea 53 4.3 0 42 2.9 0
Vomiting 46 4 0 31 1.9 0
Constipation 31 1 0 13 0 0
Abdominal distension 8 0.3 0 3.2 0.6 0
General Disorders and Administration Site Conditions
Fatigue/asthenia 45 6 0 40 4.5 0
Malaise 4.3 0 0 2.3 0.3 0
Influenza like illness 4 0 0 1.3 0 0
Infections and Infestations
Urinary tract infection 9 0.7 0 4.2 0.6 0
Upper respiratory tract infection 8 0.3 0 4.5 0.3 0
Investigations
Weight decreased 20 0.3 0 13 0.6 0
Metabolism and Nutrition Disorders
Decreased appetite 35 2.6 0 22 2.3 0
Musculoskeletal and Connective Tissue Disorders
Back pain 10 0.3 0 8 0.3 0
Arthralgia 10 0 0 6 1 0
Muscle spasms 5 0 0 1.9 0 0
Nervous System Disorder
Dizziness 14 0.3 0 10 0.6 0
Renal and urinary disorders
Renal impairment* 7 2 0.3 1 0 0.3
Dysuria 4.6 0 0 1.9 0 0
* Renal impairment includes acute kidney injury, blood creatinine increased, renal failure, and renal impairment.

Management Of Diarrhea

CONTROL

The CONTROL (NCT02400476) study was a multicenter, open-label, multi-cohort trial evaluating patients with early-stage HER2-positive breast cancer treated with NERLYNX 240 mg daily for up to one year receiving loperamide prophylaxis with additional anti-diarrheal treatment as needed or NERLYNX dose escalation with loperamide as needed. All patients in the prophylaxis cohort received loperamide 4 mg loading dose, followed by 4 mg three times a day from days 1-14, followed by 4 mg twice a day on days 15-56, followed by loperamide as needed through 1 year of treatment with NERLYNX [see DOSAGE AND ADMINISTRATION]. All patients in the dose escalation cohort received NERLYNX 120 mg for Week 1, followed by NERLYNX 160 mg for Week 2, followed by NERLYNX 240 mg for Week 3 and thereafter [see DOSAGE AND ADMINISTRATION].

Table 9 summarizes the diarrhea adverse reactions for NERLYNX with loperamide prophylaxis and NERLYNX dose escalation.

Table 9: Diarrhea in Patients Treated with NERLYNX with Antidiarrheal Prophylaxis or Dose Escalation

Loperamide Prophylaxis
n=109
NERLYNX Dose Escalation
n=60
Duration of Treatment, months
Median 11.8 12.0
Range 0.1, 12.8 0.2, 12.4
Dose Intensity, mg per day
Median 234 230
Range 46, 240 32, 236
Incidence of Diarrhea, %
Any Grade 78 98
Grade 2 25 45
Grade 3 32 13
Action Taken, %
Discontinuation due to diarrhea 18 3.3

DRUG INTERACTIONS

Effect Of Other Drugs On NERLYNX

Table 10 includes drug interactions that affect the pharmacokinetics of neratinib.

Table 10: Drug Interactions that Affect NERLYNX

Gastric Acid Reducing Agents
Clinical Impact Concomitant use of NERLYNX with a proton pump inhibitor (PPI), H2-receptor antagonist, or antacid may decrease neratinib AUC [see CLINICAL PHARMACOLOGY], which may reduce NERLYNX activity.
Prevention or Management
[see DOSAGE AND ADMINISTRATION]
Avoid concomitant use of PPIs.
Separate administration of NERLYNX at least 2 hours before or 10 hours after the H2-receptor antagonist dose.
Separate administration of NERLYNX by at least 3 hours after antacids.
Strong CYP3A4 Inhibitors
Clinical Impact Concomitant use of NERLYNX with a strong CYP3A4 inhibitor increased neratinib Cmax and AUC [see CLINICAL PHARMACOLOGY], which may increase the risk of NERLYNX toxicity.
Prevention or Management Avoid concomitant use of NERLYNX with strong CYP3A4 inhibitors.
P-gp and Moderate CYP3A4 Dual Inhibitors
Clinical Impact Concomitant use of NERLYNX with a P-gp and moderate CYP3A4 dual inhibitor may increase neratinib Cmax and AUC [see CLINICAL PHARMACOLOGY], which may increase the risk of NERLYNX toxicity.
Prevention or Management Avoid concomitant use of NERLYNX with P-gp and moderate CYP3A4 dual inhibitors.
Strong or Moderate CYP3A4 Inducers
Clinical Impact Concomitant use of NERLYNX with a strong CYP3A4 inducer reduced neratinib Cmax and AUC [see CLINICAL PHARMACOLOGY], which may reduce NERLYNX activity.
Prevention or Management Avoid concomitant use of NERLYNX with strong or moderate CYP3A4 inducers.
AUC=Area Under Curve; Cmax=Maximum Concentration

Effect Of NERLYNX On Other Drugs

Certain P-glycoprotein (P-gp) Substrates

Concomitant use of NERLYNX increased concentrations of a P-gp substrate [see CLINICAL PHARMACOLOGY], which may increase the risk of adverse reactions of these substrates. Monitor for adverse reactions of certain P-gp substrates for which minimal concentration changes may lead to serious adverse reactions.

Read the entire FDA prescribing information for Nerlynx (Neratinib Tablets)

© Nerlynx Patient Information is supplied by Cerner Multum, Inc. and Nerlynx Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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