Oncology Drug Reference Sheet: Fam-Trastuzumab Deruxtecan-Nxki

October 07, 2022 by Chelsea Backler MSN, APRN, AGCNS-BC, AOCNS®, VA-BC

Bringing the first agent to market for the indication, on August 5, 2022, the U.S. Food and Drug Administration (FDA) approved fam-trastuzumab deruxtecan-nxki (https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-option-patients-her2-positive-breast-cancer-who-have-progressed-available) (Enhertu®) for patients with unresectable or metastatic HER2-low breast cancer (https://voice.ons.org/news-and-views/what-is-her2-low-breast-cancer) based on results from the DESTINY-Breast04 trial that demonstrated improved progression-free and overall survival. FDA also gave fam-trastuzumab deruxtecan its fourth approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-fam-trastuzumab-deruxtecan-nxki-her2-mutant-non-small-cell-lung) on August 11, 2022, for unresectable or metastatic HER2-activating non-small cell lung cancer (NSCLC).



HER2-directed antibody and topoisomerase inhibitor conjugate (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true).

Mechanism of Action

A small-molecule topoisomerase I inhibitor, DXd, attaches to the HER2-directed antibody (https://www.cancer.gov/sites/g/files/xnrzdm211/files/styles/cgov_enlarged/public/cgov_image/media_image/2021-10/PenetrationofReleasedPayloadtoNeighbors.png?itok=4JjqdNHM) via a cleavable linker. After binding to HER2 on a tumor cell, fam-trastuzumab deruxtecan is internalized and undergoes intracellular linker cleavage by lysosomal enzymes, causing DNA damage and cellular death.


Approved to treat adult patients (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) with:


For breast cancer and NSCLC, administer (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) 5.4 mg/kg every three weeks. For gastric cancer, give (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) 6.4 mg/kg every three weeks.


Give as an IV infusion (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true); do not administer as a push or bolus infusion. Administer the first infusion over 90 minutes and subsequent doses over 30 minutes if the previous infusions were well tolerated. Use a 0.20 or 0.22 micron in-line polyethersulfone (PES) or polysulfone (PS) filter. Do not administer with other medications. Do not administer with sodium chloride.

Adverse Reactions

More than 20% of patients with breast cancer or NSCLC in the agent’s clinical trials reported (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) nausea, vomiting, fatigue, alopecia, constipation, musculoskeletal pain, decreased appetite, diarrhea, and respiratory infection. Laboratory abnormalities included decreased white blood cell count, hemoglobin, neutrophil count, lymphocyte count, platelet count, and hypokalemia and increased AST, ALT, and ALP. More than 20% of patients with gastric cancers in the agent’s clinical trials experienced (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) nausea, vomiting, decreased appetite, fatigue, diarrhea, constipation, pyrexia, and alopecia with labs showing decreased hemoglobin, white blood cell count, neutrophil count, lymphocyte count, platelet count, and hypokalemia; and increased AST, ALT, ALP, and bilirubin. 

Warnings and Precautions

The prescribing indications warn of neutropenia and left ventricular dysfunction (LVEF) and contain a black box warning for interstitial lung disease, pneumonitis, and embryo-fetal toxicity.

Nursing Considerations

Fam-trastuzumab deruxtecan (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) is moderately emetogenic (including delayed nausea and vomiting), and guidelines recommend premedication with antiemetics. Verify pregnancy status in patients of reproductive potential prior to starting treatment. Complete blood counts should be assessed prior to initiating therapy, prior to each dose, and as indicated. Assess LVEF prior to initiating therapy and at regular intervals throughout treatment as indicated. See the package insert (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) for dose reduction indications and schedules.  

Drug-Drug Interactions

Do not administer fam-trastuzumab deruxtecan with sodium chloride solution.

Patient Education

Female patients of reproductive (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) potential should use effective contraception during treatment and for seven months after the last dose. Males with female partners of reproductive potential should use effective contraception during treatment and for four months after the last dose. Fam-trastuzumab deruxtecan may impair male reproductive function and fertility; discuss fertility preservation with patients prior to starting therapy. Avoid breastfeeding during treatment and for seven months after the last dose. Use ONS’s patient education reference sheet (https://www.ivcanceredsheets.com/index.php/sheet-library/555-trastuzumab-deruxtecan) with your patients

Special Population Considerations

Safety and efficacy (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true) have not been established in pediatric patients. No overall differences were noted in safety or efficacy in clinical trials in patients 65 years or older compared to younger patients.

Safe Handling

Fam-trastuzumab deruxtecan is a hazardous drug (https://daiichisankyo.us/prescribing-information-portlet/getPIContent?productName=Enhertu&inline=true); use appropriate handling and disposal procedures.

Patient Assistance

Visit enhertu4u.com/patient.html (https://www.enhertu4u.com/patient.html) or call 833-364-3788.

Copyright © 2022 by the Oncology Nursing Society. User has permission to print one copy for personal or unit-based educational use. Contact pubpermissions@ons.org for quantity reprints.