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Neratinib Dosage

Medically reviewed on August 15, 2017.

Applies to the following strengths: 40 mg

Usual Adult Dose for Breast Cancer - Adjuvant

240 mg orally once a day with food, continuously for 1 year

Comments:
-Instruct patients to initiate antidiarrheal prophylaxis with loperamide along with the first dose of neratinib, and to continue using loperamide during the first 2 treatment cycles (56 days); consult the manufacturer product information for loperamide dosing recommendations.
-Advise patients to use additional antidiarrheal agents and/or make dietary changes as needed.

Use: For the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.

Renal Dose Adjustments

There are no dosage recommendations provided in the manufacturer product information; however, renal function does not have a clinically significant effect on the pharmacokinetics of this drug.

Liver Dose Adjustments

PRE-EXISTING HEPATIC IMPAIRMENT:
-MILD TO MODERATE HEPATIC IMPAIRMENT (Child-Pugh A or B): No adjustment recommended.
-SEVERE HEPATIC IMPAIRMENT (Child-Pugh C): Initial Dose: Reduce to 80 mg.

HEPATOTOXICITY DURING TREATMENT:
GRADE 3 ALT (greater than 5 to 20 times upper level of normal [ULN]) OR GRADE 3 BILIRUBIN (greater than 3 to 10 x ULN):
-Hold treatment until recovery to Grade 1 or less.
-Evaluate alternative causes.
-Resume treatment at the next lower dose level if recovery to Grade 1 or less occurs within 3 weeks.

GRADE 3 ALT OR GRADE 3 BILIRUBIN RECURRENCE (despite one dose reduction); GRADE 4 ALT (greater than 20 x ULN); OR GRADE 4 BILIRUBIN (greater than 10 x ULN): Permanently discontinue treatment; evaluate alternative causes.

COMMENTS: If Grade 3 or greater diarrhea requiring IV fluid treatment or any signs/symptoms of hepatotoxicity occurs, evaluate for changes in liver function tests, and collect fractionated bilirubin and prothrombin time.

Dose Adjustments

CONCOMITANT USE WITH GASTRIC ACID REDUCING AGENTS:
-Proton Pump Inhibitors (PPIs) and H2-Receptor Antagonists: Avoid concomitant use.
-Antacids: Separate dosing by 3 hours after antacids.

CONCOMITANT USE WITH MODERATE AND STRONG CYP450 3A4 INDUCERS AND INHIBITORS: Avoid concomitant use.

DOSE LEVEL MODIFICATIONS FOR ADVERSE REACTIONS:
-First Dose Reduction: 200 mg/day
-Second Dose Reduction: 160 mg/day
-Third Dose Reduction: 120 mg/day

DISCONTINUE TREATMENT for:
-Failure to recover to Grade 0 to 1 from treatment-related toxicity;
-Toxicities that result in a treatment delay of more than 3 weeks;
-Inability to tolerate 120 mg daily dose.

GENERAL TOXICITIES:
-GRADE 3 TOXICITY: Hold treatment until recovery to Grade 1 or less or baseline within 3 weeks of stopping treatment, then resume treatment at the next lower dose level.
-GRADE 4 TOXICITY: Permanently discontinue treatment.

DIARRHEA:
GRADE 1 (increase of more than 4 stools/day over baseline); GRADE 2 (more than 5 days: increase of 4 to 6 stools/day over baseline); GRADE 3 (more than 2 days: increase of 7 or more stools/day over baseline; incontinence; hospitalization indicated; limiting self-care activities of daily living):
-Adjust antidiarrheal treatment.
-Modify diet.
-Maintain fluid intake of approximately 2 L to avoid dehydration.
-Once event resolves to Grade 1 or less or baseline, start loperamide 4 mg with each subsequent neratinib administration.

GRADE 2 (lasting 5 days or longer); GRADE 3 (lasting longer than 2 days); ANY GRADE WITH COMPLICATED FEATURES (including dehydration, fever, hypotension, renal failure, Grade 3/4 neutropenia despite receiving optimal medical therapy):
-Adjust antidiarrheal treatment.
-Modify diet.
-Maintain fluid intake of approximately 2 L to avoid dehydration.
-If event resolves to Grade 0 to 1 in one week or less, resume treatment at the same dose.
-If event resolves to Grade 0 to 1 in longer than 1 week, resume treatment at a reduced dose.
-Once event resolves to Grade 1 or less or baseline, start loperamide 4 mg with each subsequent neratinib administration.

GRADE 4 (life-threatening consequences; urgent intervention indicated); GRADE 2 OR HIGHER RECURRENCE (at 120 mg/day):
-Permanently discontinue treatment.

COMMENTS: If Grade 3 or greater diarrhea requiring IV fluid treatment OR any signs/symptoms of hepatotoxicity occurs, evaluate for changes in liver function tests, and collect fractionated bilirubin and prothrombin time.

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available.

Other Comments

Administration Advice:
-Instruct patients to administer this drug at approximately the same time every day.
-Direct patients to swallow drug tablets whole, and not to chew, crush, or split tablets.
-Advise patients not to replace a missed dose, and to resume treatment with the next scheduled dose.

Storage Requirements:
-Store at controlled room temperature: 20 to 25 Celsius/68 to 77 Fahrenheit; excursions permitted to 15 to 30 C/59 to 86 F.

General:
-Overdosage: No specific antidote; benefit of hemodialysis is unknown.

Monitoring:
-Gastrointestinal: Diarrhea (throughout treatment); stool cultures (as clinically indicated)
-Hepatic: Total bilirubin, AST, ALT, alkaline phosphatase (prior to treatment initiation, monthly for the first 3 months of treatment, then every 3 months during treatment and as clinically indicated); fractionated bilirubin and prothrombin time (as clinically indicated)

Patient Advice:
-Avoid grapefruit products during treatment with this drug.
-This drug may cause side effects including fatigue and muscle spasms; avoid potentially dangerous activities such as driving and operating machinery until you know how this drug affects you.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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