WARNINGS
ENHERTU can cause serious side effects, including:
Lung problems that may be severe, life-threatening or that may lead to death. If you develop lung problems your healthcare provider may treat you with corticosteroid medicines. Tell your healthcare provider right away if you get any of the following signs and symptoms:
cough
other new or worsening
trouble breathing or breathing symptoms shortness of breath (such as chest tightness, wheezing)
fever
Low white blood cell count (neutropenia). Low white blood cell counts are common with ENHERTU and can sometimes be severe. Your healthcare provider will check your white blood cell counts before starting ENHERTU and before starting each dose. Tell your healthcare provider right away if you develop any signs or symptoms of an infection or have fever or chills during treatment with ENHERTU.
Heart problems that may affect your heart’s ability to pump blood. Your healthcare provider will check your heart function before starting treatment with ENHERTU. Tell your healthcare provider right away if you get any of the following signs and symptoms:
new or worsening
irregular heartbeat
shortness of breath
sudden weight gain
coughing
dizziness or feeling
feeling tired light-headed
swelling of your ankles or legs
loss of consciousness
Your healthcare provider will check you for these side effects during your treatment with ENHERTU. Your healthcare provider may reduce your dose, delay treatment or completely stop treatment with ENHERTU if you have severe side effects.
Harm to your unborn baby. Tell your healthcare provider right away if you become pregnant or think you might be pregnant during treatment with ENHERTU.
If you are able to become pregnant, your healthcare provider should do a pregnancy test before you start treatment with ENHERTU.
Females who are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for 7 months after the last dose.
Males who have female partners that are able to become pregnant should use effective birth control (contraception) during treatment with ENHERTU and for 4 months after the last dose.
See the section SIDE EFFECTS below for more information about side effects.
USES
What is ENHERTU?
ENHERTU is a prescription medicine used to treat adults who have:
human epidermal growth factor receptor 2 (HER2)-positive breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior anti-HER2 breast cancer treatment:
for metastatic disease, or
have breast cancer that has come back during or within 6 months of completing treatment for their early-stage breast cancer.
HER2-low breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received a prior chemotherapy
for metastatic disease, or
whose disease has returned during or within 6 months of completing adjuvant chemotherapy (after surgery). Your healthcare provider will perform a test to make sure ENHERTU is right for you.
Hormone receptor (HR)-positive, HER2-low or HR-positive, HER2- ultralow, breast cancer that cannot be removed by surgery or that has spread to other parts of the body (metastatic), and who have received one or more endocrine treatments for metastatic disease. Your healthcare provider will perform a test to make sure ENHERTU is right for you.
non-small cell lung cancer (NSCLC) that has a certain mutation in the HER2 gene and cannot be removed by surgery or has spread to other parts of your body (metastatic), and who have received a prior treatment. Your healthcare provider will perform a test to make sure ENHERTU is right for you.
stomach cancer called gastric or gastroesophageal junction (GEJ) adenocarcinoma that is HER2-positive and has spread to areas near your stomach (locally advanced) or that has spread to other parts of your body (metastatic), and who have received a prior trastuzumab-based regimen.
solid tumors that are HER2-positive (IHC 3+) and that cannot be removed by surgery or have spread to other parts of your body (metastatic), and who have received a prior treatment and have no other satisfactory treatment options. Your healthcare provider will perform a test to make sure ENHERTU is right for you.
It is not known if ENHERTU is safe and effective in children.
HOW TO USE
You will receive ENHERTU into your vein through an intravenous (IV) line by your healthcare provider.
ENHERTU is given 1 time every three weeks (21-day treatment cycle).
Your healthcare provider will decide how many treatments you need.
Your healthcare provider will give you medicines before your infusion to help prevent nausea and vomiting.
Your healthcare provider may slow down or temporarily stop your infusion of ENHERTU if you have an infusion-related reaction, or permanently stop ENHERTU if you have severe infusion reactions.
If you miss a planned dose of ENHERTU, call your healthcare provider right away to schedule an appointment. Do not wait until the next planned treatment cycle.
What are the possible side effects of ENHERTU?
ENHERTU can cause serious side effects. See “What is the most important information I should know about ENHERTU?”
The most common side effects of ENHERTU, when used in people with metastatic breast cancer, HER2-mutant non-small cell lung cancer, and other HER2-positive solid tumors include:
low white blood cell counts
hair loss
nausea • constipation
low red blood cell counts
low levels of blood potassium
feeling tired
decreased appetite
low platelet counts
diarrhea
increased liver function tests
muscle or bone pain
vomiting
The most common side effects of ENHERTU, when used in people with HER2-positive gastric or GEJ adenocarcinoma, include:
low red blood cell counts
diarrhea
low white blood cell counts
low levels of blood potassium
low platelet counts
vomiting
nausea • constipation
decreased appetite
fever
increased liver function tests
hair loss
feeling tired
ENHERTU may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility.
These are not all of the possible side effects of ENHERTU. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your pharmacist or healthcare provider for information about ENHERTU that is written for healthcare professionals.
What are the ingredients in ENHERTU?
Active Ingredient: fam-trastuzumab deruxtecan-nxki.
Inactive Ingredients: L-histidine, L-histidine hydrochloride
monohydrate, polysorbate 80, and sucrose.
OVERDOSE
Please call your healthcare provider for more information.
MISSED DOSE
If you miss a planned dose of ENHERTU, call your healthcare provider right away to schedule an appointment. Do not wait until the next planned treatment cycle.
STORAGE
Store vials in a refrigerator at 2-degrees C to 8-degrees C (36-degrees F to 46-degrees F) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution.
Special Handling
ENHERTU (fam-trastuzumab deruxtecan-nxki) is a hazardous drug. Follow applicable special handling and disposal procedures.1
NOTES
Medication Guide: revision date 01/2025
Prescribing Information: revision date 01/2025
Clinical Studies
Effect of CYP3A Inhibitors on DXd: Coadministration of itraconazole, a strong CYP3A inhibitor, with multiple doses of ENHERTU increased steady state AUC0-17 days of fam-trastuzumab deruxtecan-nxki by 11% and DXd by 18%. The impact of these changes is not clinically meaningful.
Effect of OATP Inhibitors on DXd: Coadministration of ritonavir, a dual inhibitor of OATP1B/CYP3A, with multiple doses of ENHERTU increased steady state AUC0-17 days of fam-trastuzumab deruxtecan-nxki by 19% and DXd by 22%. The impact of these changes is not clinically meaningful.
In Vitro Studies
Effects of DXd on CYP Enzymes: DXd does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A nor induce CYP1A2, CYP2B6, or CYP3A.
Effects of DXd on Transporters: At clinically relevant concentrations (steady-state Cmax of ~0.2 μmol/L), DXd has a low potential to inhibit OAT1 (IC50 value of 12.7 μmol/L), OAT3, OCT1, OCT2, OATP1B1 (IC50 value of 14.4 μmol/L), OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or BSEP transporters.
Effects of Other Drugs on DXd: DXd is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1, and BCRP
Before you receive ENHERTU, tell your healthcare provider about all of your medical conditions, including if you:
have lung or breathing problems
have signs or symptoms of an infection
have or have had any heart problems
are breastfeeding or plan to breastfeed. It is not known if ENHERTU passes into your breast milk. Do not breastfeed during treatment with ENHERTU and for 7 months after the last dose.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.
