Names and pronunciation
(ne-ra′-ti-nib) Nerlynx
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Drug reference
(ne-ra′-ti-nib) Nerlynx
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Func. class.: Antineoplastic
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Chem. class.: Tyrosine kinase inhibitors
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ACTION: It is an irreversible inhibitor of the epidermal growth factor receptor (EGFR) and the human epidermal recep- tor type 2 (HER2) and HER4.
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USES: For the extended adjuvant treat- ment of early-stage HER2-positive breast cancer after completion of adju- vant trastuzumab; advanced metastatic HER-2-positive breast cancer with capecitabine in those who have received ≥2 regimens
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CONTRAINDICATIONS: Hyper- sensitivity Precautions: Breastfeeding, contraception requirements, geriatric patients, hepatic disease, hepatotoxicity, infertility, preg- nancy, pregnancy testing, reproductive risk
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SIDE EFFECTS GI: Diarrhea, abdominal pain, anorexia, nausea, vomiting MS: Muscle cramps INTEG: Rash, dry skin, nail changes, fissures GU: UTI MISC: Infection
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INTERACTIONS effect—gastric Decrease: neratinib acid–reducing agents; avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists; separate by 3 hr after antacid dosing Increase: neratinib effect—strong or moderate CYP3A4 inhibitors; avoid con- comitant use Decrease: neratinib effect—strong or moderate CYP3A4 inducers; avoid con- comitant use Increase: CNS and CV adverse reactions— P-glycoprotein (P-gp) substrates; monitor for adverse reactions of narrow therapeu- tic agents that are P-gp substrates
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DOSAGE AND ROUTES Extended adjuvant treatment of early-stage HER2-positive breast cancer after completion of adjuvant trastuzumab-based therapy • Adult: PO 240 mg/day with food, × ≤1 yr Advanced metastatic HER2-positive breast cancer with capecitabine • Adult: PO 240 mg/day with food for 21 days each cycle with capecitabine 750 mg/mL bid for 14 days of a 21-day cycle Hepatic dose • Adult: PO Child-Pugh C: reduce start- ing dose to 80 mg/day
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Available forms: Tabs 40 mg
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Administer: • With food at the same time every day • Swallow tablets whole; do not chew, crush, or split • If a dose is missed, do not replace the missed dose. Resume with the next scheduled daily dose • Antidiarrheal prophylaxis is recom- mended during the first 2 cycles (56 days) of treatment, and should be initiated with the first dose of neratinib; loperamide should be taken as directed below, titrating to 1 to 2 bowel move- ments/day; additional antidiarrheal agents may be required to manage patients with loperamide-refractory diarrhea • Weeks 1 to 2 (days 1 to 14): take lo- peramide 4 mg tid • Weeks 3 to 8 (days 15 to 56): take loperamide 4 mg bid • Weeks 9 to 52 (days 57 to 365): take loperamide 4 mg as needed (max 16 mg/ day) • Store at room temperature
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Evaluate: N • Therapeutic outcome: decrease in size of cancerous tumor Teach patient/family • That infection may occur; to report urinary pain, hesitancy; skin redness, pain, heat; fever, shaking, chills • Diarrhea: to report number of loose stools per day or change in stools to provider and complete prophylaxis with loperamide • That follow-ups and lab work will be needed • Pregnancy/breastfeeding: not to use in pregnancy, breastfeeding; to use con- traception during treatment and for at least 1 mo after last dose; men with a partner who may become pregnant should use contraception during treat- ment and for at least 3 mo after last dose
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CLINICAL CONSIDERATIONS Assess • Hepatotoxicity: use with caution in those with preexisting hepatic disease; a dose reduction is required for patients with severe (Child-Pugh C) hepatic disease at baseline. Monitor LFTs (total bilirubin, AST, ALT, alkaline phosphatase) baseline, monthly × 3 mo and then q3mo thereafter and as needed. Monitor LFTs (including fractionated bilirubin and prothrombin time) in those experiencing grade 3 diar- rhea or any signs of hepatotoxicity (fatigue, nausea, vomiting, right upper quadrant tenderness, fever, rash, eosinophilia) • Geriatric patients >65 yr: monitor ge- riatric patients more closely for toxicities (vomiting, diarrhea, renal failure, dehy- dration) during treatment • Infection: may occur after completion of adjuvant trastuzumab-based therapy; assess for urinary tract infection, celluli- tis and erysipelas • Pregnancy/breastfeeding: avoid drug in females of reproductive potential; use contraception during treatment and for at least 1 mo after the last dose; can cause fetal harm or death; discontinue breast- feeding during treatment and for 1 mo after the final dose. Presence in breast milk un- known. Obtain a pregnancy test before starting treatment. Males with female part- ners of reproductive potential should avoid pregnancy and use effective contraception during treatment and ≥3 mo after last dose
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PHARMACOKINETICS Protein binding >99%; half-life 7-17 hr; fecal excretion 97.1%; metabolized in the liver by CYP3A4; avoid with strong and moderate CYP3A4 inhibitors and inducers
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• Adult: PO 240 mg/day with food, × ≤1 yr Advanced metastatic HER2-positive breast cancer with capecitabine
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• Adult: PO 240 mg/day with food for 21 days each cycle with capecitabine 750 mg/mL bid for 14 days of a 21-day cycle Hepatic dose
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• Adult: PO Child-Pugh C: reduce start- ing dose to 80 mg/day
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