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Enhertu fam-trastuzumab deruxtecan-nxki 100 mg/5mL Injection, Powder, Lyophilized, For Solution

by Daiichi Sankyo Inc. · 1 VIAL, SINGLE-DOSE in 1 CARTON (65597-406-01) / 5 mL in 1 VIAL, SINGLE-DOSE

NDC 65597-0406-01

🏷️ FDA NDC (as labeled) 65597-406-01 billing pads the product segment with a zero

Rx only Brand On market Non-controlled

🗂️ Data synced Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm

📋 All sources & update times →

This page is curated, coded, and maintained by Dr. Brian Staiger, PharmD

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

🆔 Identity & classification

FDA NDC (as labeled) 65597-406-01

Product NDC 65597-406

11-digit billing NDC 65597040601

NCPDP billing unit EA — each (per item)

RxCUI 2267576, 2267581

UNII 5384HK7574

Application # BLA761139

SPL Set ID 7e67e73e-ddf4-4e4d-8b50-09d7514910b6

DEA schedule Non-controlled

Marketing category BLA

Marketing status On market

FDA listing status Listed (active directory)

Marketing start 2019-12-20

Route INTRAVENOUS

Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION

Substance TRASTUZUMAB DERUXTECAN

GPI-14 21355070552120

GPI class Enhertu

GCN Seq No 080576

GCN 47458

HICL code 046262

Ingredient (HICL) Fam-Trastuzumab Deruxtecn-Nxki

HIC1 code V

Therapeutic class — broad (HIC1) Neoplasms

HIC2 code V1

Therapeutic class — intermediate (HIC2) Antineoplastic Drugs

HIC3 code V1K

Therapeutic class — specific (HIC3) Antineoplastics Antibody/Antibody-Drug Complexes

AHFS code 10:00.00.00

AHFS class Antineoplastic Agents

FDB label name ENHERTU 100 MG VIAL

FDB brand name Enhertu

Legend status F — Federal legend — prescription drug or device

Biologic (Purple Book) 351(a)

Why two NDCs? The FDA registers this code as 65597-406-01 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 65597-0406-01. Same drug, same package — only the format differs.

Where does this data come from?

Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

🏷️ RxNorm drug class

This medicine belongs to the HER2/neu Receptor Antagonist class.

Pharmacologic class HER2/neu Receptor Antagonist

Drug family (ATC) HER2 (Human Epidermal Growth Factor Receptor 2) inhibitors

How it works HER2/Neu/cerbB2 Antagonists

Where does this data come from?

Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

🏭 Manufacturer & labeler

LabelerDaiichi Sankyo Inc.

FDA applicationBLA761139 (BLA)

Labeler code65597

First marketedDec 2019

Product typeHuman Prescription Drug

Portfolio8 products on file

🔎 All NDCs from Daiichi Sankyo Inc.

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).

Where does this data come from?

Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

🩺 Clinical

Label name ENHERTU 100 MG VIAL Ingredient Fam-Trastuzumab Deruxtecn-Nxki

📗 Our plain-language guide HelloPharmacist

Enhertu is what's called an antibody-drug conjugate — it's designed to be more targeted than standard chemotherapy. Think of it as a smart delivery system: an antibody seeks out an...
What exactly is Enhertu and how is it different from regular chemotherapy?
Enhertu is given as an IV infusion — directly into a vein — at a clinic or infusion center. Treatments are generally scheduled once every 3 weeks. Before each infusion, you'll rece...
How will I receive Enhertu, and how often do I need to come in?

📖 Read our full Fam-trastuzumab deruxtecan-nxki Injection guide →

Patient education

📘 MedlinePlus patient leaflet ↗

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →

Where does this data come from?

Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

🧪 Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

UNII 4QD397987E
An amino acid used as a buffer and stabilizer in medications. It helps maintain the pH balance and protects the active drug from breaking down during storage and use.
UNII X573657P6P
Histidine monohydrochloride monohydrate is an amino acid salt used as a buffer in medicines. It helps maintain the proper acidity level of liquid formulations to keep the drug stable and effective.
UNII 6OZP39ZG8H
Polysorbate 80 is a synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together in medications and improves how the product disperses in the body.
UNII C151H8M554
A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.

4 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?

Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?

No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.

Why might an inactive ingredient be missing?

Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.

Can inactive ingredients matter?

Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

💲 Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price system	Per mL	Per package
Retail pharmacies payNADAC · weekly	Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo	$2,581.49	$12,907.44 / 5 ml
Medicare drug plans payPart D · quarterly	No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9358	$32.874 / J9358 unit	—

Where does this data come from?

NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

🧾 Billing & reimbursement

FDA NDC (as labeled)65597-406-01

11-digit billing NDC65597-0406-01

Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)

HCPCS J-codeJ9358

DescriptorInjection, fam-trastuzumab deruxtecan-nxki, 1 mg

Billing units / pkg100 units

Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk

Where does this data come from?

The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

🔁 Therapeutic equivalents

Product	Labeler	Pack	NADAC/unit	TE	Status	Price vs. this
Enhertu 100 mg/5mLthis 65597-0406-01	Daiichi	1 vial	—	—	FDA listed	—

About this product: this is a biologic. Biologics don't have small-molecule generics — competition comes from FDA-licensed biosimilars (shown above), not generics.

Where does this data come from?

Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

⏳ Availability & biosimilar status

🏛️

2019

First FDA approval

Dec 2019

📍

2026

Currently FDA-listed

7 years listed

🛡️

2031

Latest patent/protection listed

not a guaranteed launch date

🧬Biologic — competition comes from biosimilars

Biologics have no small-molecule generics; biosimilar competition is tracked in the FDA Purple Book.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Dec 2031. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.

📅 FDA approved Dec 20, 2019 ⏳ ~5.3 yr to latest listed protection

Why the date isn’t exact: Biosimilar timing can change because patents may be challenged, settled, licensed, added or removed, and litigation can move the real date earlier or later.

FDA Purple Book — biosimilars & interchangeables ⓘ

Reference product

Enhertufam-trastuzumab deruxtecan-nxki

🔒 No FDA-licensed biosimilars or interchangeable biosimilars are listed yet for this biologic. It currently has no biosimilar competition in the FDA Purple Book.

Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.

Patents & exclusivity — FDA Purple Book

Exclusivity RefProduct

2019 2021 2023 2025 2027 2029 2031

Today

LOE

Biologic patent Exclusivity

🏛️Reference-product exclusivity

A flat 12 years of FDA market protection from first licensure. No biosimilar can be licensed before it ends — regardless of patents.

🧪Listed biologic patents

Patents the reference maker lists covering the molecule, formulation, or manufacturing. A biosimilar generally can’t launch until these resolve.

🔁Interchangeability

An interchangeable biosimilar may be substituted at the pharmacy (state laws vary). The first one can earn its own exclusivity period.

🛈 What do these terms mean?

Biologic patent: A patent the reference product’s maker has publicly listed. A biosimilar generally can’t launch until these expire — unless they’re invalidated or resolved in a settlement.
Reference-product exclusivity: A flat 12 years of FDA market protection from the biologic’s first licensure (the BPCIA). No biosimilar can be licensed before it ends, regardless of patents.
Interchangeable exclusivity: The first interchangeable biosimilar can earn a period as the only interchangeable version (pharmacists can substitute it without the prescriber).
Earliest biosimilar (LOE): The latest of all the dates above — the soonest a biosimilar can realistically reach the market. Litigation and settlements can move it earlier.

Biologics have no small-molecule “generics” — competition comes from FDA-licensed biosimilars, tracked in the FDA Purple Book.

FDA exclusivity

Code	What it grants	Expires
RefProduct	Reference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this date	Dec 20, 2031

Common questions

Is there a biosimilar for ENHERTU 100 MG VIAL?

No FDA-licensed biosimilar is currently listed for this biologic in the FDA Purple Book.

Why do different websites show different biosimilar dates?

Biosimilar availability isn’t based on one single date. Some sources use the reference-product exclusivity, some use the last listed patent, and patent litigation, settlements, and licenses can all change the real-world launch date. This page shows the underlying Purple Book dates so you can see why estimates differ.

Can a biosimilar launch before the last patent expires?

Sometimes. A biosimilar maker may settle with the reference manufacturer or receive a license to launch earlier. In other cases, the last listed protection delays competition.

What does “current Purple Book estimate” mean?

It means we’re using the latest patent and exclusivity dates currently listed in the FDA Purple Book. It is not a guaranteed launch date.

What does “FDA listed” mean?

It means the product appears in the FDA’s official directory. That’s a good sign a product exists for the U.S. market, but on its own it does not confirm a pharmacy can get it today. Where we have recent retail pricing data, we label it “Availability likely” instead.

What does a patent or protection date mean here?

It’s the latest date currently listed in the FDA Purple Book for a patent or exclusivity on the reference biologic. It can affect when a biosimilar becomes widely available — but it is not a guaranteed launch date. Settlements and licenses can move the real date earlier or later.

Built from the FDA Purple Book Patent List (patents the reference-product sponsor has publicly listed under the BPCIA) plus reference-product exclusivity. Biosimilars cannot launch until these clear; patent litigation and settlements can shift the real date. Biologics have no small-molecule generics — competition comes from FDA-licensed biosimilars, not the Orange Book.

Where does this data come from?

Patents and exclusivity from the FDA Purple Book (biologics), refreshed from public FDA data. Biosimilar launch timing is an estimate, not a guarantee.

🗺️ Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for 65597-0406-01, not the drug overall. Other pack sizes report separately.

💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.

📅 Q1 2025 – Q4 2025 · 4 quarters of data

ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.

Prescriptions last 4 qtrs

17.5K

Units reimbursed last 4 qtrs

50K

Gross reimbursed last 4 qtrs

$129.12M

Avg / prescription

$7,382.83

Avg / unit

$2,581.51

Latest quarter Q4 2025

3.4KRx

Fee-for-service vs managed care ⓘ

33% FFS 67% MCO

Fee-for-service · 5,775 Rx Managed care · 11,714 Rx

State Medicaid map

Units reimbursed · per 100k residents

1.448.4

gray = no data reported ⓘ

Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.

Tap or hover a state

…for its Medicaid breakdown

🏆 Top states by units · per 100k residents

1 Hawaii 48.4 /100k

2 D.C. 41.8 /100k

3 Maryland 41.7 /100k

4 South Dakota 40.9 /100k

5 Nevada 37.8 /100k

6 Massachusetts 36.9 /100k

7 Indiana 31.6 /100k

8 Maine 27.8 /100k

National units — by quarter

💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

📊 Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Enhertu — the program that covers self-administered drugs. 1 manufacturer.

⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Enhertu. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.

Period

Total Part D spend

$7.57M

Claims incl. refills

605

Beneficiaries

221

Spend / beneficiary

$34,233.88

Spend / claim

$12,505.27

Trend by period

💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

🔬 Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for Enhertu (this brand).

Top reported reactions

Nausea1,219

Death1,213

Disease Progression1,077

Interstitial Lung Disease1,020

Fatigue797

Diarrhoea575

Vomiting560

Age at onset

Child1

Adult789

Elderly441

Reporter sex

Male · 12%

Female · 88%

Serious outcomes

Death2,575

Hospitalization2,439

Life-threatening330

Disabling73

Reports over time (by year) — tap or hover for the count & year

Most recent year is provisional (FAERS lags ~3 months).

Where does this data come from?

Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

📦 Packaging — all sizes for this product

Package NDC	Description	Marketing start	Status
65597-0406-01 You're viewing this	1 VIAL, SINGLE-DOSE in 1 CARTON (65597-406-01) / 5 mL in 1 VIAL, SINGLE-DOSE	2019-12-20	Active

🧭 About this NDC listing & data coverage

Finished prescription product

What data is (and isn’t) available for this NDC — tap to expand

NDC identity (package / product / labeler codes)	✓ Available
Labeler	✓ Available
Product & package description	✓ Available
Marketing category & status	✓ Available
Active ingredient / dosage form / route	✓ Available
FDA label (SPL via DailyMed)	✓ Available
Package photos	— Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured)	✓ Available
NADAC pharmacy acquisition price (CMS)	— Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data	✓ Available
HCPCS J-code billing crosswalk	✓ Available
Medicaid utilization (CMS SDUD)	✓ Available

“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?

The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.

Is the NDC printed on the package the same as the 11-digit billing NDC?

Yes, they identify this exact package in different formats. The FDA registers it as 65597-406-01, which is what is printed on the packaging and shown on DailyMed. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero: 65597-0406-01, written without dashes as 65597040601. The Identity section at the top of this page lists every form of this code.

What do the three segments of this NDC mean?

In 65597-0406-01, the first segment (65597) is the labeler code FDA assigned to Daiichi Sankyo Inc.; the middle segment (0406) identifies this specific product — its ingredient, strength, and dosage form; and the last segment (01) identifies this exact package size and type. Together they name one specific package of one specific product.

Is this package still being marketed?

Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Daiichi Sankyo Inc.. Listing status can change — the directory data on this page refreshes weekly.

Who lists this product with the FDA?

Daiichi Sankyo Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.

Do I need a prescription for this product?

This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.

Does this product have a billing J-code?

Yes — this NDC cross-references HCPCS code J9358 for medical-claim billing (typically used when a product is administered in a clinical setting rather than dispensed at a retail pharmacy). See the Billing section on this page.

This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.

Where does this data come from?

Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.

📄 Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Jump with a chip, search within the label, or expand everything.

🚨 Boxed Warning 🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 💬 Medication Guide

🚨 Boxed Warning ~1 min read ▾

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY Interstitial Lung Disease (ILD) and pneumonitis, including severe, life-threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis.

Advise patients of the risk and the need to immediately report symptoms [see Dosage and Administration (2.3) , Warnings and Precautions (5.1) ] . Embryo-Fetal Toxicity: Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1 , 8.3) ] .

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY See full prescribing information for complete boxed warning. Interstitial lung disease (ILD) and pneumonitis, including severe, life threatening, and fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms.

Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms. ( 2.3 , 5.1 ) Exposure to ENHERTU during pregnancy can cause embryo-fetal harm.

Advise patients of these risks and the need for effective contraception. ( 5.4 , 8.1 , 8.3 )

🎯 Indications and Usage ~3 min read ▾

1 INDICATIONS AND USAGE ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for: HER2-Positive Early Breast Cancer as neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer, as determined by an FDA-authorized test followed by a taxane, trastuzumab, and pertuzumab (THP). ( 1.1 ) as adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment.

( 1.1 ) HER2-Positive Metastatic Breast Cancer in combination with pertuzumab as first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test. ( 1.2 ) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen either in the metastatic setting, or, in the neoadjuvant or adjuvant setting and have developed disease recurrence during or within six months of completing therapy.

( 1.2 ) HER2-Low and HER2-Ultralow Metastatic Breast Cancer as monotherapy for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by an FDA-authorized test, that has progressed on one or more endocrine therapies in the metastatic setting. ( 1.3 ) as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer, as determined by an FDA-authorized test, who have received a prior chemotherapy in the metastatic setting; or developed disease recurrence during or within 6 months of completing adjuvant chemotherapy.

( 1.3 ) HER2-Mutant Unresectable or Metastatic Non-Small Cell Lung Cancer as monotherapy for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, as detected by an FDA-authorized test, and who have received a prior systemic therapy* ( 1.4 ) HER2-Positive Locally Advanced or Metastatic Gastric Cancer as monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH positive) gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.

( 1.5 ) HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors as monotherapy for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumors who have received prior systemic treatment and have no satisfactory alternative treatment options* ( 1.6 ) * These indications are approved under accelerated approval based on objective response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

( 14.3 , 14.5 )

1.1HER2-Positive Early Breast Cancer ENHERTU followed by a taxane, trastuzumab, and pertuzumab (THP) is indicated for the neoadjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer as determined by an FDA-authorized test [see Dosage and Administration (2.1) ]. ENHERTU is indicated for the adjuvant treatment of adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following neoadjuvant trastuzumab (with or without pertuzumab) and taxane-based treatment.

1.2HER2-Positive Metastatic Breast Cancer ENHERTU, in combination with pertuzumab, is indicated for the first-line treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer, as determined by an FDA-authorized test [see Dosage and Administration (2.1) ]. ENHERTU, as monotherapy, is indicated…

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. ( 2.2 , 2.4 ) For intravenous infusion only . Do not administer as an intravenous push or bolus.

DO NOT use Sodium Chloride Injection, USP. ( 2.4 ) Premedicate for prevention of chemotherapy-induced nausea and vomiting. ( 2.2 ) HER2-Positive Early Breast Cancer Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 4 cycles, followed by THP regimen for 4 cycles.

( 2.2 , 2.3 ) Post Neoadjuvant: ENHERTU 5.4 mg/kg every 3 weeks for 14 cycles unless disease recurrence or unacceptable toxicity. ( 2.2 , 2.3 ) HER2-Positive, HER2-Low, or HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (IHC 3+) Solid Tumors: ENHERTU 5.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity. ( 2.2 , 2.3 ) HER2-Positive First-line Metastatic Breast Cancer: ENHERTU 5.4 mg/kg every 3 weeks in combination with pertuzumab until disease progression or unacceptable toxicity.

Cycle 1, Day 1: ENHERTU 5.4 mg/kg followed by pertuzumab 840 mg. ( 2.2 , 2.3 ) Subsequent cycles, Day 1: ENHERTU 5.4 mg/kg followed by pertuzumab 420 mg. ( 2.2 , 2.3 ) HER2-Positive Gastric Cancer: 6.4 mg/kg every 3 weeks until disease progression or unacceptable toxicity.

( 2.2 , 2.3 ) Management of adverse reactions (ILD, neutropenia, thrombocytopenia, or left ventricular dysfunction) may require temporary interruption, dose reduction, or discontinuation of ENHERTU. ( 2.3 )

2.1Patient Selection HER2-Positive Early Breast Cancer Select patients for the treatment of HER2-positive early breast cancer with ENHERTU based on HER2-positive (IHC 3+ or ISH+) status [see Clinical Studies (14.1) ]. HER2-Positive Metastatic Breast Cancer Select patients for treatment of unresectable or metastatic HER2-positive breast cancer with ENHERTU in combination with pertuzumab based on confirmed HER2-positive status or HER2 gene amplification (IHC 3+ or ISH+) [see Clinical Studies (14.2) ] . HER2-Low or HER2-Ultralow Unresectable or Metastatic Breast Cancer Select patients for treatment of unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer with ENHERTU based on HER2 expression [see Clinical Studies (14.3) ] .

HER2-Mutant Unresectable or Metastatic NSCLC Select patients for the treatment of unresectable or metastatic HER2-mutant NSCLC with ENHERTU based on the presence of activating HER2 (ERBB2) mutations in tumor or plasma specimens [see Clinical Studies (14.4) ] . If no mutation is detected in a plasma specimen, test tumor tissue. HER2-Positive Locally Advanced or Metastatic Gastric Cancer Select patients with locally advanced or metastatic HER2-positive gastric cancer based on HER2 protein overexpression or HER2 gene amplification (IHC 3+ or IHC 2+/ISH+).

Reassess HER2 status if it is feasible to obtain a new tumor specimen after prior trastuzumab-based therapy and before treatment with ENHERTU. HER2-Positive (IHC 3+) Unresectable or Metastatic Solid Tumors Select patients for treatment of unresectable or metastatic solid tumors with ENHERTU based on HER2-positive (IHC 3+) specimens [see Clinical Studies (14.6) ] . An FDA-authorized test for the detection of HER2-positive (IHC 3+) solid tumors for treatment with ENHERTU is not currently available.

Additional Patient Selection Information Information on FDA-authorized tests for the detection of HER2 protein expression, HER2 gene amplification, and activating HER2 mutations is available at: http://www.fda.gov/CompanionDiagnostics.

2.2Recommended Dosage Do not substitute ENHERTU for or with trastuzumab or ado-trastuzumab emtansine. Slow or interrupt the infusion rate if the patient develops infusion-related symptoms. Permanently discontinue ENHERTU in case of severe infusion reactions. Premedication ENHERTU is highly emetogenic [see Adverse Reactions (6.1) ] , which includes delayed nausea and/or vomiting. Administer prophylactic antiemetic medications…

💊 Dosage Forms and Strengths 42 words ▾

3 DOSAGE FORMS AND STRENGTHS For injection: 100 mg of fam-trastuzumab deruxtecan-nxki as a white to yellowish white lyophilized powder in a single-dose vial for reconstitution and further dilution For injection: 100 mg lyophilized powder in a single-dose vial ( 3 )

⛔ Contraindications 8 words ▾

4 CONTRAINDICATIONS None . None. ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Neutropenia: Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Manage through treatment interruption or dose reduction. ( 2.3 , 5.2 ) Left Ventricular Dysfunction (LVD): Assess left ventricular ejection fraction (LVEF) prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated.

Manage through treatment interruption or discontinuation. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure (CHF). ( 2.3 , 5.3 )

5.1Interstitial Lung Disease/Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU [see Adverse Reactions (6.1) ] . A higher incidence of Grade 1 and 2 ILD/pneumonitis has been observed in patients with moderate renal impairment. Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms.

Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging.

Consider consultation with a pulmonologist. For asymptomatic (Grade 1) ILD, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). Withhold ENHERTU until recovery [see Dosage and Administration (2.3) ] .

In cases of symptomatic ILD (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Permanently discontinue ENHERTU in patients who are diagnosed with symptomatic (Grade 2 or greater) ILD [see Dosage and Administration (2.3) ] . HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, ILD occurred in 12% of patients.

Median time to first onset was 5.5 months (range: 0.9 to 31.5). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.9% of patients treated with ENHERTU. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), ILD occurred in 12% of patients.

Median time to first onset was 8.0 months (range: 0.6 to 33.8). Fatal outcomes due to ILD and/or pneumonitis occurred in 0.5% of patients treated with ENHERTU in combination with pertuzumab. ENHERTU followed by THP In patients treated with ENHERTU 5.4 mg/kg followed by THP in DESTINY-Breast11, ILD occurred in 4.4% of patients.

Median time to first onset was 2.7 months (range: 1.1 to 6.0). Fatal outcomes due to ILD and/or pneumonitis occurred in one patient (0.3%) treated with ENHERTU followed by THP. HER2-Positive Locally Advanced or Metastatic Gastric Cancer (6.4 mg/kg) In patients with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg, ILD occurred in 10% of patients.

Median time to first onset was 2.8 months (range: 1.2 to 21).

5.2Neutropenia Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction [see Dosage and Administration (2.3) ] .

HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy In patients treated with ENHERTU 5.4 mg/kg, a decrease in neutrophil count was reported in 65% of patients. Nineteen percent had Grade 3 or 4 decreased neutrophil count. Median time to first onset of decreased neutrophil count was 22 days (range: 2 to 939).

Febrile neutropenia was reported in 1% of patients. ENHERTU in Combination with Pertuzumab In patients treated with ENHERTU 5.4 mg/kg in…

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Interstitial Lung Disease/Pneumonitis [see Warnings and Precautions (5.1) ] Neutropenia [see Warnings and Precautions (5.2) ] Left Ventricular Dysfunction [see Warnings and Precautions (5.3) ] The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with: HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and HER2-Positive (including IHC 3+) Solid Tumors are decreased white blood cell count, nausea, decreased hemoglobin, decreased neutrophil count, decreased lymphocyte count, fatigue, decreased platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, increased blood alkaline phosphatase, vomiting, alopecia, constipation, decreased blood potassium, decreased appetite, diarrhea, and musculoskeletal pain.

( 6.1 ) HER2-Positive Early Breast Cancer are decreased hemoglobin, increased alanine aminotransferase, increased aspartate aminotransferase, decreased white blood cell count, nausea, peripheral neuropathy, diarrhea, decreased neutrophil count, alopecia, fatigue, decreased lymphocyte count, rash, musculoskeletal pain, decreased blood potassium, constipation, vomiting, stomatitis, and decreased appetite. ( 6.1 ) HER2-Positive Metastatic Breast Cancer in Combination with Pertuzumab are decreased white blood cell count, decreased hemoglobin, decreased neutrophil count, nausea, increased alanine aminotransferase, diarrhea, increased aspartate aminotransferase, decreased lymphocyte count, decreased platelet count, increased blood alkaline phosphatase, decreased blood potassium, fatigue, alopecia, vomiting, upper respiratory tract infection, constipation, decreased appetite, decreased weight, COVID-19, musculoskeletal pain, increased blood bilirubin, and abdominal pain.

( 6.1 ) HER2-Positive Gastric Cancer are decreased hemoglobin, decreased white blood cell count, decreased neutrophil count, decreased lymphocyte count, decreased platelet count, nausea, decreased appetite, increased aspartate aminotransferase, fatigue, increased blood alkaline phosphatase, increased alanine aminotransferase, diarrhea, decreased blood potassium, vomiting, constipation, increased blood bilirubin, pyrexia, and alopecia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Daiichi Sankyo, Inc. at 1-877-437-7763 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. HER2-Positive, HER2-Low, and HER2-Ultralow Breast Cancer, HER2-Mutant NSCLC, and Solid Tumors (Including IHC 3+) (5.4 mg/kg) ENHERTU as Monotherapy The pooled safety population described in WARNINGS and PRECAUTIONS reflects exposure to ENHERTU 5.4 mg/kg intravenously every 3 weeks in 2233 patients in Study DS8201-A-J101 (NCT02564900), DESTINY-Breast01, DESTINY-Breast02, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Breast06, DESTINY-Lung01, DESTINY-Lung02, DESTINY-CRC02, and DESTINY-PanTumor02.

Among these patients, 67% were exposed for greater than 6 months and 39% were exposed for greater than 12 months. In this pooled safety population, the most common (≥20%) adverse reactions (including laboratory abnormalities) were decreased white blood cell count (73%), nausea (72%), decreased hemoglobin (67%), decreased neutrophil count (65%), decreased lymphocyte count (60%), fatigue (55%), decreased platelet count (48%), increased aspartate aminotransferase (46%), increased alanine aminotransferase (43%), increased blood alkaline phosphatase (39%), vomiting (38%), alopecia (37%), constipation (32%), decreased blood potassium (32%), decreased appetite (31%), diarrhea (30%), and musculoskeletal pain (24%).

ENHERTU…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Lactation: Advise not to breastfeed. (8.2) Females and Males of Reproductive Potential: Verify pregnancy status of females prior to initiation of ENHERTU. ( 8.3 )

8.1Pregnancy Risk Summary Based on its mechanism of action, ENHERTU can cause fetal harm when administered to a pregnant woman. There are no available data on the use of ENHERTU in pregnant women. In postmarketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death ( see Data ).

Based on its mechanism of action, the topoisomerase inhibitor component of ENHERTU, DXd, can also cause embryo-fetal harm when administered to a pregnant woman because it is genotoxic and targets actively dividing cells [see Clinical Pharmacology (12.1) , Nonclinical Toxicology (13.1) ] . Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months after the last dose of ENHERTU ( see Clinical Considerations ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received ENHERTU during pregnancy or within 7 months prior to conception for oligohydramnios. If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with community standards of care. Data Human Data There are no available data on the use of ENHERTU in pregnant women.

In postmarketing reports in pregnant women receiving a HER2-directed antibody, cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported. These case reports described oligohydramnios in pregnant women who received a HER2-directed antibody either alone or in combination with chemotherapy. In some case reports, amniotic fluid index increased after use of a HER2-directed antibody was stopped.

Animal Data There were no animal reproductive or developmental toxicity studies conducted with fam-trastuzumab deruxtecan-nxki.

8.2Lactation Risk Summary There is no data regarding the presence of fam-trastuzumab deruxtecan-nxki in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.

8.3Females and Males of Reproductive Potential Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception Females ENHERTU can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose.

Males Because of the potential for genotoxicity, advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose [see Nonclinical Toxicology (13.1) ] . Infertility Based on findings in animal toxicity studies, ENHERTU may impair male reproductive function and fertility [see Nonclinical Toxicology (13.1) ] .

🤰 Pregnancy ~2 min read ▾

Animal Data There were no animal reproductive or developmental toxicity studies conducted with fam-trastuzumab deruxtecan-nxki.

🧒 Pediatric Use 144 words ▾

8.4Pediatric Use Safety and effectiveness of ENHERTU have not been established in pediatric patients. Animal Data Juvenile animal studies have not been conducted with fam-trastuzumab deruxtecan-nxki. In a six-week repeat-dose toxicity study in rats, intravenous administration of fam-trastuzumab deruxtecan-nxki resulted in incisor tooth toxicity including single cell necrosis in the base area (e.g., ameloblasts, odontoblasts) and degeneration of the enamel at ≥60 mg/kg (approximately ≥9 times the human recommended dose of 5.4 mg/kg based on AUC), abnormal formation or hypoplasia of the dentin, hemorrhage in the sub-enamel organ tissue, and focal lack of the cementum at 197 mg/kg (approximately 19 times the human recommended dose of 5.4 mg/kg based on AUC).

Degeneration of the enamel organ, abnormal dentin formation, hemorrhage in the sub-enamel organ tissue, focal lack of the cementum, and root fracture were observed at 197 mg/kg following a 9-week recovery period.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use ENHERTU as Monotherapy Of the 2233 patients treated with ENHERTU 5.4 mg/kg, 28% were 65 years or older and 6% were 75 years or older. No overall differences in efficacy within clinical studies were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged 65 years or older (56%) as compared to younger patients (49%).

Of the 125 patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma treated with ENHERTU 6.4 mg/kg in DESTINY-Gastric01, 56% were 65 years or older and 14% were 75 years or older. No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. ENHERTU in Combination with Pertuzumab In patients with HER2-positive unresectable or metastatic breast cancer treated with ENHERTU 5.4 mg/kg in combination with pertuzumab (N=431), 17% were 65 years or older and 3% were 75 years or older.

No overall differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients. ENHERTU followed by THP Of the 320 patients with HER2-positive early breast cancer treated with ENHERTU 5.4 mg/kg followed by THP, 12% were 65 years or older and 1.6% were 75 years or older. No overall difference in efficacy was observed between patients ≥65 years of age compared to younger patients.

There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged 65 years or older (38%) as compared to younger patients (30%).

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody-drug conjugate. The antibody is a humanized anti-HER2 IgG1. The small molecule, DXd, is a topoisomerase I inhibitor attached to the antibody by a cleavable linker.

Following binding to HER2 on tumor cells, fam-trastuzumab deruxtecan-nxki undergoes internalization and intracellular linker cleavage by lysosomal enzymes. Upon release, the membrane-permeable DXd causes DNA damage and apoptotic cell death.

12.2Pharmacodynamics Exposure-Response Relationships Exposure-response relationship for efficacy has not been fully characterized. Higher systemic exposure to fam-trastuzumab deruxtecan-nxki was associated with a higher incidence rate of any grade ILD. Cardiac Electrophysiology At the dosage of ENHERTU 6.4 mg/kg every 3 weeks, a mean increase in the QTc interval >20 ms was not observed.

12.3Pharmacokinetics The pharmacokinetics of fam-trastuzumab deruxtecan-nxki and its payload DXd were evaluated in patients with cancer and are presented as mean (% coefficient of variation), unless otherwise specified. At a dose of 5.4 mg/kg, the maximum concentration (C max ss ) of fam-trastuzumab deruxtecan-nxki is 132 µg/mL (20%) and of DXd is 4.7 ng/mL (48%) and the AUC ss of fam-trastuzumab deruxtecan-nxki is 772 µg∙day/mL (27%) and of DXd is 29 ng∙day/mL (48%). At a dose of 6.4 mg/kg, the C max,ss of fam-trastuzumab deruxtecan-nxki is 126 µg/mL (18%) and of DXd is 5.2 ng/mL (42%) and the AUC ss of fam-trastuzumab deruxtecan-nxki is 743 µg∙day/mL (26%) and of DXd is 33 ng∙day/mL (43%), respectively.

Following a single dose, C max and AUC of fam-trastuzumab deruxtecan-nxki and DXd increase in a dose proportional manner over a dose range of 3.2 mg/kg to 8 mg/kg (approximately 0.5 to 1.25 times the highest approved dose). Accumulation of fam-trastuzumab deruxtecan-nxki is approximately 1.4-fold at steady-state (Cycle 3). Distribution The estimated volume of distribution of the central compartment (Vc) of fam-trastuzumab deruxtecan-nxki is

2.7L (% CV 16%). DXd plasma protein binding is approximately 97% and the blood-to-plasma ratio is approximately 0.6 in vitro. Elimination The median elimination half-life of fam-trastuzumab deruxtecan-nxki is 5.4 to 5.7 days. The estimated systemic clearance of fam-trastuzumab deruxtecan-nxki is

0.4L/day (24%). The median elimination half-life of DXd is 5.4-6.1 days. The estimated systemic clearance of DXd is 18 L/h (28%).

Metabolism The monoclonal antibody is expected to be degraded into small peptides and amino acids via catabolic pathways. DXd is primarily metabolized by CYP3A4. Specific Populations No clinically significant differences in the pharmacokinetics of fam-trastuzumab deruxtecan-nxki or DXd were observed for age (20-96 years); race (Asian [48%] vs Non-Asian [52%]), including White (43%), and Black or African American (1.9%); sex; body weight (27-138 kg); tumor types; mild hepatic impairment; and mild or moderate renal impairment.

The pharmacokinetics of fam-trastuzumab deruxtecan-nxki or DXd in patients with moderate to severe hepatic impairment or severe renal impairment is unknown. Drug Interaction Studies Clinical Studies No clinically significant differences in pharmacokinetics of fam-trastuzumab deruxtecan-nxki or DXd were observed when used concomitantly with itraconazole (strong CYP3A inhibitor) or ritonavir (strong CYP3A inhibitor and OATP inhibitor). In Vitro Studies CYP450 Enzymes : DXd does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A nor induce CYP1A2, CYP2B6, or CYP3A.

UGT Enzymes: DXd is not a substrate of UGT. Transporter Systems : DXd is not an inhibitor of OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3, MATE1, MATE2-K, P-gp, BCRP, or BSEP. DXd is a substrate of OATP1B1, OATP1B3, MATE2-K, P-gp, MRP1, and BCRP.

12.6Immunogenicity The observed incidence of anti-drug antibodies (ADA) is highly dependent on the sensitivity and specificity of the assay.…

🧬 Mechanism of Action 65 words ▾

📦 How Supplied / Storage and Handling 91 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied/Storage ENHERTU (fam-trastuzumab deruxtecan-nxki) for injection is a white to yellowish white lyophilized powder supplied as: Carton Contents NDC One 100 mg single-dose vial NDC 65597-406-01 Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution [see Dosage and Administration (2.4) ] .

Special Handling ENHERTU (fam-trastuzumab deruxtecan-nxki) is a hazardous drug. Follow applicable special handling and disposal procedures. 1

📦 Storage and Handling 59 words ▾

Store vials in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of reconstitution. Do not freeze. Do not shake the reconstituted or diluted solution [see Dosage and Administration (2.4) ] . Special Handling ENHERTU (fam-trastuzumab deruxtecan-nxki) is a hazardous drug. Follow applicable special handling and disposal procedures. 1

📋 Description 182 words ▾

11 DESCRIPTION Fam-trastuzumab deruxtecan-nxki is a HER2-directed antibody and topoisomerase inhibitor conjugate. Fam-trastuzumab deruxtecan-nxki is an antibody-drug conjugate (ADC) composed of three components: 1) a humanized anti-HER2 IgG1 monoclonal antibody (mAb), covalently linked to 2) a topoisomerase I inhibitor, via 3) a tetrapeptide-based cleavable linker. Deruxtecan is composed of a protease-cleavable maleimide tetrapeptide linker and the topoisomerase inhibitor, DXd, which is an exatecan derivative.

The antibody is produced in Chinese hamster ovary cells by recombinant DNA technology, and the topoisomerase inhibitor and linker are produced by chemical synthesis. Approximately 8 molecules of deruxtecan are attached to each antibody molecule. Fam-trastuzumab deruxtecan-nxki has the following structure: ENHERTU (fam-trastuzumab deruxtecan-nxki) is a sterile, white to yellowish white, preservative-free lyophilized powder in single-dose vials.

Each vial delivers 100 mg of fam-trastuzumab deruxtecan-nxki, L-histidine (4.45 mg), L-histidine hydrochloride monohydrate (20.2 mg), polysorbate 80 (1.5 mg), and sucrose (450 mg). Following reconstitution with 5 mL of Sterile Water for Injection, USP, the resulting concentration of fam-trastuzumab deruxtecan-nxki is 20 mg/mL with a pH of 5.5. The resulting solution is administered by intravenous infusion following dilution.

Chemical Structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Interstitial Lung Disease Inform patients of the risks of severe or fatal ILD. Advise patients to contact their healthcare provider immediately for any of the following: cough, shortness of breath, fever, or other new or worsening respiratory symptoms [see Warnings and Precautions (5.1) ] .

Neutropenia Advise patients of the possibility of developing neutropenia and to immediately contact their healthcare provider should they develop a fever, particularly in association with any signs of infection [see Warnings and Precautions (5.2) ] . Left Ventricular Dysfunction Advise patients to contact their healthcare provider immediately for any of the following: new onset or worsening shortness of breath, cough, fatigue, swelling of ankles/legs, palpitations, sudden weight gain, dizziness, loss of consciousness [see Warnings and Precautions (5.3) ] .

Embryo-Fetal Toxicity Inform female patients of the potential risk to a fetus. Advise female patients to contact their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.4) , Use in Specific Populations (8.1) ] . Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for 7 months after the last dose [see Use in Specific Populations (8.3) ] .

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for 4 months after the last dose [see Use in Specific Populations (8.3) ] . Lactation Advise women not to breastfeed during treatment and for 7 months after the last dose of ENHERTU [see Use in Specific Populations (8.2) ] . Infertility Advise males of reproductive potential that ENHERTU may impair fertility [see Use in Specific Populations (8.3) ] .

💬 Medication Guide ~3 min read ▾

This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 05/2026 Medication Guide ENHERTU ® (en-HER-too) (fam-trastuzumab deruxtecan-nxki) for injection What is the most important information I should know about ENHERTU?

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 trouble breathing or shortness of breath fever other new or worsening breathing symptoms (such as chest tightness, wheezing) 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 and during treatment if needed. Tell your healthcare provider right away if you get any of the following signs and symptoms: new or worsening shortness of breath coughing feeling tired swelling of your ankles or legs irregular heartbeat sudden weight gain dizziness or feeling light-headed 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 " What are the possible side effects of ENHERTU? " for more information about side effects. What is ENHERTU? ENHERTU is a prescription medicine used to treat adults with: Human epidermal growth factor receptor 2 (HER2)-positive stage II or stage III early breast cancer followed by a taxane, trastuzumab and pertuzumab (THP) before surgery.

Your healthcare provider will perform a test to make sure ENHERTU is right for you. HER2-positive breast cancer that cannot be removed by surgery or has spread to other parts of the body (metastatic) in combination with pertuzumab as your first treatment. Your healthcare provider will perform a test to make sure ENHERTU in combination with pertuzumab is right for you.

ENHERTU alone is a prescription medicine used to treat adults with: HER2-positive early breast cancer who have received trastuzumab (with or without pertuzumab) and taxane-based treatment before surgery and have cancer remaining in the tissue removed during surgery. 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…

Glossary — plain-language definitions of medical terms used in this label:

in vitro: In a laboratory dish or test tube rather than in a living person or animal; results may not carry over to people.

abdominal pain: Pain, cramping, or discomfort felt anywhere in the belly area.

accumulation: A buildup of a medicine in the body when new doses are taken before earlier ones are fully removed.

adjuvant: Extra treatment given after the main treatment to lower the chance that the cancer comes back.

adverse reaction: An unwanted or harmful effect that a medicine causes in the body.

Adverse Reactions: Unwanted or harmful effects that people experienced while taking a medicine, listed on its official label.

alkaline phosphatase: An enzyme measured in a blood test; higher levels can point to problems with the liver, bile ducts, or bones.

alopecia: Loss of hair from the scalp or body.

AUC: A measure of total drug exposure over time, showing how much medicine the blood is exposed to overall.

BCRP: A protein pump that moves certain drugs out of cells, affecting how much of the drug is absorbed.

bilirubin: A yellow substance the liver normally clears from the blood; high levels can turn the skin or the whites of the eyes yellow.

bolus: A single dose given all at once, often as a quick push into a vein.

Boxed Warning: The strongest safety warning the FDA can require, set inside a bold black border because the risk it describes can be very serious.

clearance: How quickly the body removes a medicine from the blood, usually through the liver and kidneys.

Clinical Pharmacology: The label section explaining how a medicine works in the body and how the body processes it.

Clinical Studies: The label section summarizing the research trials used to show that a medicine works and is acceptably safe.

constipation: Having bowel movements less often than usual, or passing stools that are hard, dry, and difficult to move.

contraception: Methods used to prevent pregnancy, such as birth control pills, condoms, or an intrauterine device.

Contraindications: A list of situations or health conditions in which a medicine should not be used because the chance of harm is too high.

CYP1A2: A liver enzyme that breaks down certain medicines and whose activity can be changed by cigarette smoke.

CYP2C19: A liver enzyme that breaks down certain medicines, such as some stomach-acid drugs and drugs that help prevent blood clots.

CYP2C9: A liver enzyme that breaks down certain medicines, including some blood thinners and anti-inflammatory drugs.

CYP2D6: A liver enzyme that breaks down many medicines; people inherit different versions, so it works faster in some and slower in others.

CYP3A4: One of the most important liver and gut enzymes, responsible for breaking down a large share of all medicines.

diarrhea: Loose, watery bowel movements that happen more often than normal.

Distribution: How a medicine spreads from the blood into the body's tissues and organs after it is absorbed.

Dosage and Administration: The label section explaining how much of a medicine to use and how to take or give it.

dose reduction: Lowering the amount of a medicine, often to ease side effects or fit a person's needs.

dyspnea: The medical word for shortness of breath, or the feeling that you cannot get enough air.

efficacy: How well a treatment works under the controlled conditions of a clinical study.

ejection fraction: The share of blood in the heart's main pumping chamber that gets pushed out with each beat, given as a percentage.

Elimination: The overall removal of a medicine from the body by breaking it down and passing it out.

embryo-fetal toxicity: Harm to a developing baby in the womb, such as birth defects, slowed growth, or loss of the pregnancy.

estimated background risk: The normal chance that any pregnancy will have a birth defect or problem, even without taking any medicine.

febrile: Having a fever, or relating to a fever.

febrile neutropenia: A fever that happens when infection-fighting white blood cells are very low, which can be a sign of serious infection.

fertility: The natural ability to become pregnant or to father a child.

fetal harm: Injury or damage to a developing baby while it is growing inside the womb.

Full Prescribing Information: The complete, detailed label for a prescription medicine that follows the summary highlights.

gestational age: How far along a pregnancy is, usually counted in weeks from the mother's last menstrual period.

Half-life: The time it takes for the amount of medicine in the blood to drop by half.

heart failure: A condition in which the heart cannot pump blood as well as it should, causing tiredness, breathlessness, and swelling.

hemoglobin: The iron-containing protein inside red blood cells that carries oxygen throughout the body.

hemorrhage: Bleeding, especially heavy or uncontrolled bleeding, either inside the body or from an outside wound.

hepatic impairment: Reduced liver function, meaning the liver does not work as well as normal at processing substances, including medicines.

How Supplied/Storage and Handling: The label section describing the forms and strengths a medicine comes in and how to store it properly.

immunogenicity: The tendency of a medicine to make the body produce antibodies against it, which can affect how well it works or cause reactions.

incidence: How often a new event, such as a side effect, happens in a group of people over a set period of time.

Indications and Usage: The label section stating which medical conditions the FDA has officially approved the medicine to treat, prevent, or manage.

infusion: Slowly delivering fluid or medicine into a vein over a period of time, usually through a drip.

inhibitor: A substance that blocks an enzyme or transporter, which can raise the levels of drugs it normally handles.

interstitial lung disease: A group of conditions in which the tissue around the lungs' air sacs becomes scarred or inflamed, making breathing harder.

intravenous: Given directly into a vein through a needle or thin tube; often written as IV.

lactation: The making and release of milk from a mother's breasts after giving birth.

lyophilized: Freeze-dried into a powder that is mixed with liquid before it is given.

Mechanism of Action: How a medicine produces its effect in the body, described at the level of cells or body chemistry.

Medication Guide: An FDA-approved handout written for patients that explains important safety information about certain medicines in plain language.

Metabolism: How the body chemically changes a medicine, usually in the liver, into other substances.

monotherapy: Treatment using a single medicine by itself.

NDC: A unique number that identifies a specific medicine, its maker, strength, and package size.

neoadjuvant: Treatment given before the main treatment, such as before surgery, usually to shrink a tumor first.

neonatal: Relating to a newborn baby during its first four weeks of life.

neutropenia: A low level of neutrophils, a type of white blood cell that fights infection, which can make it easier to catch infections.

neutrophil: A type of white blood cell that is one of the body's main defenders against infection.

Nonclinical Toxicology: The label section summarizing safety findings from laboratory and animal studies, rather than from studies in people.

OATP: A group of transporter proteins that carry certain drugs into cells, especially in the liver.

objective response rate: The percentage of patients in a study whose tumors shrink by a set amount after treatment.

P-gp: A protein pump in cells that pushes certain drugs back out, limiting how much is absorbed or reaches tissues.

palpitations: The feeling that your heart is racing, pounding, fluttering, or skipping beats.

Patient Counseling Information: The label section telling health professionals what to explain to patients about using a medicine safely.

peripheral neuropathy: Damage to the nerves outside the brain and spinal cord, often causing numbness, tingling, or pain in the hands and feet.

Pharmacokinetics: The study of how the body takes in a medicine, spreads it around, breaks it down, and removes it over time.

pneumonitis: Inflammation of the lung tissue that is not caused by an infection and can lead to cough and breathlessness.

Prescribing Information: The official, detailed document approved by the FDA that tells health professionals how to use a prescription medicine.

protein binding: How much of a medicine sticks to proteins in the blood instead of moving freely through the body.

pyrexia: A raised body temperature; a fever.

QTc: A number from a heart tracing (ECG) that measures the heart's electrical recovery time, adjusted for the heart rate.

receptor: A special docking spot on a cell that a medicine or natural body chemical attaches to in order to trigger an effect.

reconstitution: Mixing a powdered medicine with a liquid to prepare it for use, following the label's directions.

renal impairment: Reduced kidney function, meaning the kidneys do not filter waste and fluid from the blood as well as normal.

reproductive potential: The ability to have children, meaning a person who could become pregnant or could father a child.

single-dose vial: A small container holding one dose of medicine, meant to be used once and then thrown away.

stomatitis: Soreness, swelling, or sores on the lining inside the mouth.

substrate: A drug or other substance that a particular enzyme or transporter acts on.

taper: Gradually lowering a dose in steps before stopping, rather than quitting all at once.

thrombocytopenia: A low level of platelets, the blood cells that help form clots, which can lead to easier bruising or bleeding.

transporter: A protein that moves drugs across cell membranes, carrying them either into or out of cells.

UGT: A family of enzymes that attach a sugar-like molecule to a drug, making it easier for the body to remove.

upper respiratory tract infection: An infection of the nose, sinuses, or throat, such as the common cold.

Use in Specific Populations: The label section describing how a medicine affects particular groups, such as pregnant people, children, or older adults.

volume of distribution: A calculated value showing how widely a medicine spreads into body tissues versus staying in the blood.

Warnings and Precautions: The label section describing serious risks to know about and safety steps to follow while using a medicine.

wheezing: A high-pitched whistling sound made while breathing, usually when the airways are narrowed.

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

← 65597-0203-05 · Daiichi 65597-0407-20 · Daiichi →

For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.

Enhertu fam-trastuzumab deruxtecan-nxki 100 mg/5mL Injection, Powder, Lyophilized, For Solution

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