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ZIIHERA zanidatamab-hrii 50 mg/mL Injection, Powder, Lyophilized, For Solution — NDC 68727-950-02 (Billing 68727-0950-02)

by Jazz Pharmaceuticals, Inc. · 2 VIAL, SINGLE-DOSE in 1 CARTON / 6 mL in 1 VIAL, SINGLE-DOSE

This is a package of ZIIHERA zanidatamab-hrii 50 mg/mL Injection, Powder, Lyophilized, For Solution from Jazz Pharmaceuticals, Inc., marketed since Nov 2024 and currently FDA-listed. It is this product's only package size.

NDC 68727-0950-02
🏷️ FDA NDC (as labeled) 68727-950-02 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Sep 10, 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

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

NDC database record

One package, one record: these facts belong to NDC 68727-950-02 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
68727 labeler · 950 product · 02 package
Package marketed since
Nov 20, 2024
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 6872795002 3
Medicaid fills, this package
12 prescriptions in the last four reported quarters
FDA record last changed
Sep 10, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 68727-950-02
Product NDC 68727-950
11-digit billing NDC 68727095002
NCPDP billing unit EA — each (per item)
RxCUI 2698206, 2698212
UNII Z20OC92TDI
Application # BLA761416
SPL Set ID ae5d9425-fae5-4541-a158-150998343348
Established class (EPC) Bispecific HER2-directed Antibody
Mechanism of action HER2-directed Antibody Interactions
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2024-11-20
Route INTRAVENOUS
Dosage form INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION
Substance ZANIDATAMAB
Biologic (Purple Book) 351(a)

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GCN Seq No 086773
GCN 56542
HICL code 050014
Ingredient (HICL) Zanidatamab-Hrii
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 ZIIHERA 300 MG VIAL
FDB brand name Ziihera
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 086773
  • GCN: 56542
  • HICL (First Databank): 050014
  • AHFS class code: 10:00.00.00
  • RxCUI (RxNorm): 2698206
Why two NDCs? The FDA registers this code as 68727-950-02 — 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 → 68727-0950-02. 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 (Human Epidermal Growth Factor Receptor 2) inhibitors class.

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

Clinical

Label name ZIIHERA 300 MG VIAL Ingredient Zanidatamab-Hrii
📗 Our plain-language guide HelloPharmacist
  • It treats adults with HER2-positive stomach, gastroesophageal junction and esophageal adenocarcinoma, given with chemotherapy and sometimes tislelizumab-jsgr. It also treats previo...
  • It is given as an IV infusion by your care team every 2 or 3 weeks, depending on your cancer and weight. You will get premedication beforehand to reduce infusion reactions. Food do...
  • Call your care team right away, drink more fluids and start your anti-diarrhea medicine as directed. Diarrhea can be severe with this treatment. If you are on chemotherapy, you wil...
  • Common ones are diarrhea, nausea, vomiting, decreased appetite, fatigue, low potassium, rash and nerve tingling. Infusion reactions can also happen. Tell your team about anything t...
📖 Read our full Zanidatamab-Hrii guide →

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.

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 systemPer mLPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $3,765.58 $45,186.99 / 12 ml
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J9276 $25.663 / J9276 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)68727-950-02
11-digit billing NDC68727-0950-02
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ9276
DescriptorINJECTION, ZANIDATAMAB-HRII, 2 MG
Billing units / pkg150 units
How the units are derivedThis package is 2 EA; the HCPCS unit is 2 MG, so one package = 150 billing units.
Medicare Part B spend (2026 (Q1))$2,825,500 · 145 claims · $19,486.21 per claim (all NDCs under J9276)
Crosswalk sourcePDAC NDC-HCPCS crosswalk (DME MAC / DMEPOS)
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.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
68727-0950-02 You're viewing this Main listing 2 VIAL, SINGLE-DOSE in 1 CARTON / 6 mL in 1 VIAL, SINGLE-DOSE 2024-11-20 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Ziihera 50 mg/mLthis 68727-0950-02 Jazz 2 vials — — 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

🏛️
2024
First FDA approval
Nov 2024
📍
2026
Currently FDA-listed
2 years listed
🛡️
2036
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 Nov 2036. This may affect when biosimilars become widely available, but it is not a guaranteed launch date.
📅 FDA approved Nov 20, 2024 ⏳ ~10.1 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
Ziiherazanidatamab-hrii
🔒 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
2024 2026 2028 2030 2032 2034 2036
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
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateNov 20, 2036
Common questions
Is there a biosimilar for ZIIHERA 300 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.

What it looks like

Color White
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

🧪 Avoiding an ingredient? See Zanidatamab-Hrii inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

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

  • 0.63 mg / 1 mL UNII 7T1F30V5YH
    A synthetic emulsifier derived from sorbitol and oleic acid. It helps mix oil and water-based ingredients together and keeps them from separating in liquid formulations.
  • 4.3 mg / 1 mL UNII V8ZGC8ISR3
    Sodium succinate anhydrous is a salt derived from succinic acid. It acts as a buffer to help maintain the medicine's pH and may also serve as a filler to give the tablet or capsule proper volume and texture.
  • 4.3 mg / 1 mL UNII AB6MNQ6J6L
    Succinic acid is an organic acid derived from natural sources or chemical synthesis. In medications, it functions as a buffer to help maintain the proper pH level and may also serve as a preservative or flavor enhancer in formulations.
  • 567 mg / 1 mL 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.

Manufacturer & labeler

LabelerJazz Pharmaceuticals, Inc.
FDA applicationBLA761416 (BLA)
Labeler code68727
First marketedNov 2024
Product typeHuman Prescription Drug
Portfolio9 products on file

More NDCs from Jazz Pharmaceuticals, Inc. labeler code 68727

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.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). 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 📋 Description 💬 Information for Patients 💬 Medication Guide 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🚨 Boxed Warning ~1 min read ▾

WARNING: DIARRHEA AND EMBRYO-FETAL TOXICITY ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr, can cause severe diarrhea, including life threatening and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated.

Interrupt, reduce the dose or discontinue ZIIHERA based on severity [see Dosage and Administration ( 2.4 ), Warnings and Precautions ( 5.1 ), Use in Specific Populations ( 8.5 )] . Embryo-Fetal Toxicity: Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 , 8.3 )] .

WARNING: DIARRHEA and EMBRYO‑FETAL TOXICITY See full prescribing information for complete boxed warning. • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr can cause severe diarrhea, including life threatening, and fatal cases. Use antidiarrheal prophylaxis during the first cycle when ZIIHERA is given in combination with these drugs. Manage with antidiarrheals and supportive measures as clinically indicated.

Interrupt, reduce the dose or discontinue ZIIHERA based on severity. ( 2.4 , 5.1 , 8.5 ) • Exposure to ZIIHERA during pregnancy can cause embryo-fetal harm. Advise patients of the risk and need for effective contraception.

( 5.2 )

🎯 Indications and Usage ~2 min read ▾

1 INDICATIONS AND USAGE ZIIHERA is a bispecific HER2-directed antibody indicated for: Gastroesophageal Adenocarcinoma (GEA) • in combination with fluoropyrimidine- and platinum-containing chemotherapy, and tislelizumab-jsgr, as first-line treatment of adult patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test. ( 1.1 ) • in combination with fluoropyrimidine- and platinum-containing chemotherapy, as first-line treatment of adult patients with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test.

( 1.1 ) Biliary Tract Cancer (BTC) • for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) BTC, as detected by an FDA-authorized test.* ( 1.2 ) *This indication is approved under accelerated approval based on overall 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(s). ( 1 )

1.1Gastroesophageal Adenocarcinoma (GEA) • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab-jsgr, is indicated for the first-line treatment of adult patients with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] . • ZIIHERA, in combination with fluoropyrimidine- and platinum-containing chemotherapy, is indicated for the first-line treatment of adult patients with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] .

1.2Biliary Tract Cancer (BTC) ZIIHERA, as a single agent, is indicated for the treatment of adults with previously treated, unresectable or metastatic HER2-positive (IHC 3+) biliary tract cancer (BTC), as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] . This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies ( 14.2 )] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Premedicate all patients to reduce the risk of infusion-related reactions (IRRs). ( 2.2 ) • Administer loperamide during the first cycle to patients receiving ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy for diarrhea prophylaxis. ( 2.2 ) Gastroesophageal Adenocarcinoma (GEA): • Patients weighing less than 70 kg: ZIIHERA 1,800 mg intravenously every 3 weeks or 1,200 mg every 2 weeks infusion in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr.

( 2.3 ) • Patients weighing 70 kg or greater: ZIIHERA 2,400 mg intravenously every 3 weeks or 1,600 mg every 2 weeks in combination with fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr. ( 2.3 ) Biliary Tract Cancer: ZIIHERA 20 mg/kg intravenously every 2 weeks. ( 2.3 )

2.1Patient Selection HER2-Positive Gastroesophageal Adenocarcinoma (GEA) Select patients for treatment of unresectable locally advanced or metastatic GEA based on HER2-positive status (IHC 3+ or IHC 2+/ISH+), as detected by FDA-authorized tests [see Clinical Studies ( 14.1 )] . Information on FDA-authorized tests for HER2 protein expression and gene amplification in gastric, gastroesophageal junction, or esophageal adenocarcinoma is available at: http://www.fda.gov/CompanionDiagnostics . Biliary Tract Cancer (BTC) Select patients for treatment of unresectable or metastatic biliary tract cancer based on HER2-positive (IHC 3+) tumor specimens, as detected by an FDA-authorized test [see Clinical Studies ( 14.2 )] .

Information on FDA-authorized tests for HER2 protein expression in biliary tract cancers is available at: http://www.fda.gov/CompanionDiagnostics.

2.2Premedications and Important Administration Information Premedicate all patients 30 to 60 minutes prior to each dose of ZIIHERA to reduce the risk of infusion-related reactions [see Warnings and Precautions ( 5.4) ] : • Administer acetaminophen, an antihistamine (such as diphenhydramine) and a corticosteroid (such as hydrocortisone). ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr Antidiarrheal prophylaxis: • Administer loperamide 4 mg twice daily beginning on Day 1 and continue for at least 7 days during the first cycle of treatment. • If patients experience Grade 1 or higher diarrhea during the first cycle, continue prophylaxis with loperamide 4 mg twice daily for at least the first 7 days of each subsequent cycle [see Warnings and Precautions ( 5.1 )].

Fluorouracil-containing regimens: • When ZIIHERA is administered in combination with fluorouracil-containing regimens, administer fluorouracil as an intravenous infusion. Do NOT administer fluorouracil as an intravenous bolus due to the potential increase in diarrhea [see Warnings and Precautions ( 5.1 )] . Missed dose ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr If a planned dose of ZIIHERA is delayed or missed, administer the dose as soon as possible if 7 days or fewer have passed since the scheduled time.

If more than 7 days have passed since the planned dose, withhold ZIIHERA and resume on day 1 of the next cycle. ZIIHERA as a single agent If a planned dose of ZIIHERA is delayed or missed, administer the dose as soon as possible; do not wait until the next planned dose. Adjust the administration schedule to maintain a 2-week interval between doses.

2.3Recommended Dosage Gastroesophageal Adenocarcinoma (GEA) Administer ZIIHERA as an intravenous infusion until disease progression or unacceptable toxicity at the recommended dosages presented in Table 1: Table 1: Dosage recommendations for patients with GEA Patient body weight Dosage < 70 kg: • 1,800 mg every 3 weeks or • 1,200 mg every 2 weeks ≥ 70 kg: • 2,400 mg every 3 weeks or • 1,600 mg every 2 weeks Refer to the Prescribing Information of each of the indiv… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 29 words ▾

3 DOSAGE FORMS AND STRENGTHS For injection: 300 mg white lyophilized powder in a single-dose vial. For injection: 300 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 • Left Ventricular Dysfunction: Assess left ventricular ejection fraction (LVEF) prior to initiation of ZIIHERA and at regular intervals during treatment. Withhold or permanently discontinue ZIIHERA based on severity. ( 2.4 , 5.3 ) • Infusion-Related Reactions (IRRs): Premedicate before each infusion of ZIIHERA.

Interrupt the infusion, decrease the infusion rate, and/or permanently discontinue ZIIHERA based on severity. ( 2.2 , 2.4 , 5.4 )

5.1Diarrhea ZIIHERA can cause severe diarrhea. When ZIIHERA is used in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr, severe, life threatening, and fatal cases of diarrhea can occur despite loperamide prophylaxis [see Adverse Reactions ( 6.1 ), Use in Specific Populations ( 8.5 )] . The risk of severe and life threatening diarrhea is higher when ZIIHERA is administered with chemotherapy and tislelizumab-jsgr, with a higher risk in patients aged 65 years or older compared to younger patients [see Geriatric Use ( 8.5 )] .

Advise patients to increase oral fluids, begin antidiarrheals, and notify their healthcare provider immediately if diarrhea occurs [see Patient Counseling Information ( 17 )] . Administer antidiarrheal prophylaxis with loperamide in cycle 1 for all patients receiving ZIIHERA in combination with fluoropyrimidine- and platinum-containing chemotherapy with or without tislelizumab-jsgr. Begin loperamide at the first loose stool when ZIIHERA is administered in combination with chemotherapy or as a single agent.

Administer fluids, electrolytes, and additional antidiarrheal agents as necessary. When ZIIHERA was used in combination with chemotherapy with or without tislelizumab-jsgr, 9% of patients had a dose reduction of ZIIHERA due to diarrhea and concomitant agents were dose reduced in 22% of patients. Before modifying the dose of ZIIHERA, evaluate, modify or discontinue drug(s) contributing to diarrhea in accordance with their respective prescribing information.

Withhold, reduce the dose, or permanently discontinue ZIIHERA based on severity [see Dosage and Administration ( 2.2 , 2.4 )] . In a Phase 2 study evaluating ZIIHERA in combination with FOLFOX in patients with GEA, 57% of patients who received a fluorouracil bolus without loperamide prophylaxis (N=14), experienced Grade 3 diarrhea, while 30% of patients who did not receive a fluorouracil bolus but received loperamide prophylaxis (N=10) experienced Grade 3 diarrhea. If treating patients with ZIIHERA in combination with FOLFOX, do not administer the fluorouracil bolus.

Gastroesophageal Adenocarcinoma (GEA) In Combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab: When ZIIHERA was used in combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab-jsgr, diarrhea was reported in 85% of 330 patients treated in clinical studies, including Grade 4 (2.1%), Grade 3 (24%), and Grade 2 (31%) events. Fatal outcomes resulting from diarrhea occurred in 1.5% of patients. Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 3.9% of patients.

In cycle 1, diarrhea at Grade 4 severity occurred in 1.5% and Grade 3 severity occurred in 15% of patients despite use of loperamide prophylaxis. The median time to onset for cycle 1 diarrhea was 6 days and median time to resolution was 18 days. In Combination with fluoropyrimidine- and platinum-containing chemotherapy: When ZIIHERA was used in combination with fluoropyrimidine- and platinum-containing chemotherapy , diarrhea was reported in 81% of 395 patients treated in clinical studies, including Grade 4 (1.3%), Grade 3 (20%) and Grade 2 (33%).

Diarrhea leading to dose reduction of ZIIHERA occurred in 10% of patients, and permanent discontinuation of ZIIHERA occurred in 1.8% of patients. In cycle 1, diarrhea at Grade 4 severity occurred in 0.8% and Grade 3 severity occurred… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described in greater detail in other sections of the labeling: • Diarrhea [see Warnings and Precautions ( 5.1 )] • Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.2) ] • Left Ventricular Dysfunction [see Warnings and Precautions (5.3 )] • Infusion-Related Reactions [see Warnings and Precautions ( 5.4 )] • Most common adverse reactions (≥ 20%) with ZIIHERA in combination with chemotherapy and tislelizumab-jsgr were diarrhea, nausea, decreased appetite, vomiting, hypokalemia, fatigue, rash, peripheral neuropathy, and IRR.

( 6.1 ) • Most common adverse reactions (≥ 20%) with ZIIHERA in combination with chemotherapy were diarrhea, nausea, vomiting, decreased appetite, fatigue, hypokalemia, peripheral neuropathy, IRR, and rash. ( 6.1 ) • Most common adverse reactions (≥ 20%) with ZIIHERA as a single agent were diarrhea, IRR, abdominal pain, and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Jazz Pharmaceuticals, Inc. at 1‑800‑520‑5568 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. Gastroesophageal Adenocarcinoma (GEA) The pooled safety population of ZIIHERA described in WARNINGS AND PRECAUTIONS, reflects exposure to ZIIHERA in combination with chemotherapy, with or without tislelizumab-jsgr, in 725 patients with GEA from four open-label studies, including HERIZON-GEA-01 (N=605), ZWI-ZW25-201 (N=46), ZWI-ZW25-101 (N=41), and BGB-A317-ZW25-101 (N=33) at doses of 1,800 mg every 3 weeks (< 70 kg), 2,400 mg every 3 weeks (≥ 70 kg), 1,200 mg every 2 weeks (< 70 kg), 1,600 mg every 2 weeks (≥ 70 kg), or other doses.

Among the 330 patients who received ZIIHERA in combination with chemotherapy and tislelizumab-jsgr for GEA, 64% were exposed for 6 months or longer, and 41% were exposed for 1 year or more. Among the 395 patients who received ZIIHERA in combination with chemotherapy for GEA, 57% were exposed for 6 months or longer, and 34% were exposed for 1 year or more. Biliary Tract Cancer (BTC) The pooled safety population of ZIIHERA administered 20 mg/kg intravenously as a single agent, described in WARNINGS AND PRECAUTIONS reflects exposure in 233 patients in two single-arm, open-label studies (ZWI-ZW25-101 and HERIZON-BTC-01): 109 patients with biliary tract cancer, and 124 patients with other cancers.

Among 233 patients who received ZIIHERA as a single agent, 39% were exposed for 6 months or longer, and 17% were exposed for greater than one year. Gastroesophageal Adenocarcinoma (GEA) (HERIZON-GEA-01) The safety of ZIIHERA administered in combination with chemotherapy, with or without tislelizumab-jsgr for the treatment of GEA was evaluated in 901 patients [see Clinical Studies ( 14.1 )] . Patients received ZIIHERA by IV infusion every 3 weeks at 1,800 mg (< 70 kg body weight) or 2,400 mg (≥ 70 kg), with or without tislelizumab-jsgr and an investigator choice of a fluoropyrimidine- and platinum-based chemotherapy (CAPOX or FP) or trastuzumab with CAPOX or FP [see Clinical Studies ( 14.1 )] .

Treatment in each arm continued until disease progression or unacceptable toxicity. ZIIHERA in combination with tislelizumab-jsgr and chemotherapy Sixty-three percent (63%) of patients were exposed to ZIIHERA for 6 months or longer and 39% 1 year or longer). Serious adverse reactions occurred in 59% of patients who received ZIIHERA.

Serious adverse reactions in > 2% of patients included diarrhea (17%), infusion-related reactions (5%), vomiting (4.8%), hypokalemia (4.4%), acute kidney injury (3.7%), pneumonia (3.7%), nausea (2.4%), decreased appetite (2.4%), and anemia (2.4%). Fatal adverse reactions occurred in 2.4% of patients who received ZIIHERA in com… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS • Females and Males of Reproductive Potential: Verify the pregnancy status of females prior to initiation of ZIIHERA. ( 8.3 )

8.1Pregnancy Risk Summary Based on mechanism of action, ZIIHERA can cause fetal harm when administered to a pregnant woman. There are no human or animal data on the use of ZIIHERA in pregnancy. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Use of ZIIHERA is not recommended during pregnancy (see CLINICAL CONSIDERATIONS). Advise patients of potential risks to a fetus. 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, background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received ZIIHERA during pregnancy or within 4 months prior to conception for oligohydramnios.

If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with local standard of care.

8.2Lactation Risk Summary There are no data on the presence of zanidatamab‑hrii in human milk, the effects on the breastfed child, or the effects on milk production. Published data suggest human IgG is present in human milk but does not enter neonatal or infant circulation in substantial amounts. Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for ZIIHERA treatment and any potential adverse effects on the breastfed child from ZIIHERA or from the underlying maternal condition.

This consideration should also take into account the ZIIHERA half-life of approximately 24 days and a washout period of 4 months [see Clinical Pharmacology ( 12.3 )] .

8.3Females and Males of Reproductive Potential ZIIHERA can cause fetal harm when administered to a pregnant woman [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1 )] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to the initiation of ZIIHERA [see Use in Specific Populations ( 8.1 )] . Contraception Females ZIIHERA can cause embryo-fetal harm when administered during pregnancy.

Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose of ZIIHERA.

8.4Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients.

8.5Geriatric Use Gastroesophageal Adenocarcinoma (GEA) ZIIHERA in combination with tislelizumab-jsgr and chemotherapy Of 302 patients randomized to ZIIHERA in combination with chemotherapy and tislelizumab-jsgr in HERIZON-GEA-01, there were 139 (46%) patients 65 years of age and older. One hundred and six (35%) were aged 65-74 years old and 33 (11%) were aged 75 years or older [see Clinical Studies ( 14.1 )] . There was a higher incidence of Grade ≥ 3 adverse reactions observed in patients 65 years of age and older (87%) as compared to younger patients (80%).

The incidence of Grade 3 or 4 diarrhea was higher in patients 65 years and older (32%) compared to patients younger than 65 years (20%). There was an increased incidence of fatal adverse reactions in patients 65 years and older (4.4%); including acute kidney injury (N=2), cardiac failure, dehydration, hypovolemic shock and intestinal obstruction (all N=1), compared to younger patients (0.6%), including diarrhea (N=1). ZIIHERA in combination with chemotherapy Of 304 patients randomized to ZIIHERA in combination with chemotherapy in HERIZON-GEA-01, there were 130 (43%) patients 65 years of age and older.

One hundred (33%) were aged 65-74 years old and 30 (… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy 176 words ▾

8.1Pregnancy Risk Summary Based on mechanism of action, ZIIHERA can cause fetal harm when administered to a pregnant woman. There are no human or animal data on the use of ZIIHERA in pregnancy. In literature reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death.

Use of ZIIHERA is not recommended during pregnancy (see CLINICAL CONSIDERATIONS). Advise patients of potential risks to a fetus. 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, background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Monitor women who received ZIIHERA during pregnancy or within 4 months prior to conception for oligohydramnios.

If oligohydramnios occurs, perform fetal testing that is appropriate for gestational age and consistent with local standard of care.

🧒 Pediatric Use 15 words ▾

8.4Pediatric Use Safety and efficacy of ZIIHERA have not been established in pediatric patients.

🧓 Geriatric Use ~1 min read ▾

8.5Geriatric Use Gastroesophageal Adenocarcinoma (GEA) ZIIHERA in combination with tislelizumab-jsgr and chemotherapy Of 302 patients randomized to ZIIHERA in combination with chemotherapy and tislelizumab-jsgr in HERIZON-GEA-01, there were 139 (46%) patients 65 years of age and older. One hundred and six (35%) were aged 65-74 years old and 33 (11%) were aged 75 years or older [see Clinical Studies ( 14.1 )] . There was a higher incidence of Grade ≥ 3 adverse reactions observed in patients 65 years of age and older (87%) as compared to younger patients (80%).

The incidence of Grade 3 or 4 diarrhea was higher in patients 65 years and older (32%) compared to patients younger than 65 years (20%). There was an increased incidence of fatal adverse reactions in patients 65 years and older (4.4%); including acute kidney injury (N=2), cardiac failure, dehydration, hypovolemic shock and intestinal obstruction (all N=1), compared to younger patients (0.6%), including diarrhea (N=1). ZIIHERA in combination with chemotherapy Of 304 patients randomized to ZIIHERA in combination with chemotherapy in HERIZON-GEA-01, there were 130 (43%) patients 65 years of age and older.

One hundred (33%) were aged 65-74 years old and 30 (10%) were aged 75 years or older [see Clinical Studies ( 14.1 )] . No overall differences in safety were observed between patients 65 years of age and older and younger adult patients. Biliary Tract Cancer Of the 80 patients who received ZIIHERA for unresectable or metastatic biliary tract cancer in HERIZON-BTC-01 as a single agent, there were 39 (49%) patients 65 years of age and older.

Thirty-seven (46%) were aged 65-74 years old and 2 (3%) were aged 75 years or older [see Clinical Studies ( 14.2 )] . No overall differences in safety or effectiveness were observed between patients 65 years of age and older compared to younger adult patients.

🧬 Clinical Pharmacology ~2 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Zanidatamab-hrii is a bispecific HER2-directed antibody that binds to extracellular domains 2 (ECD2) and 4 (ECD4) on HER2. Similar to other HER2-directed antibodies, in vitro binding of zanidatamab-hrii with HER2 causes clustering and results in internalization leading to a reduction of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).

These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.

12.2Pharmacodynamics Zanidatamab-hrii exposure-response relationships for safety and efficacy and the time course of pharmacodynamic response have not been fully characterized. Cardiac Electrophysiology A mean increase in the QTc interval > 20 ms is unlikely at the approved recommended dosage.

12.3Pharmacokinetics Zanidatamab-hrii pharmacokinetics were characterized at steady-state in patients with BTC and GEA at the approved recommended dosages and are presented as mean (coefficient of variation [CV]%) in Table 9. Table 9: Zanidatamab-hrii steady-state pharmacokinetics in patients with BTC and GEA at the approved recommended dosages Parameters ZIIHERA Dosage 1,800 mg /2,400 mg every 3 weeks in patients with GEA (%CV) 1,200 mg /1,600 mg every 2 weeks in patients with GEA (%CV) 20 mg/kg every 2 weeks in patients with BTC (%CV) C min (µg/mL) 176 (39%) 203 (36%) 200 (52%) C avg (µg/mL) 319 (27%) 319 (27%) 319 (36%) C max (µg/mL) 783 (20%) 609 (21%) 624 (26%) The C max of zanidatamab-hrii is dose proportional and the total systemic exposure (AUC) of zanidatamab-hrii is greater than dose proportional.

Steady state was approached after approximately 16 weeks following multiple doses. Zanidatamab-hrii median C trough accumulation is 1.8-fold. Distribution Zanidatamab-hrii volume of distribution is

8.1L (28.4%). Elimination Zanidatamab-hrii elimination half-life is 24 days with an apparent clearance (CL) of

0.3L/day (30%). Metabolism Zanidatamab‑hrii is expected to be metabolized into small peptides by catabolic pathways. Specific Populations No clinically meaningful differences in the pharmacokinetics of zanidatamab-hrii were observed based on age (22 to 87 years), sex, body weight (35 to 142 kg), race (White 39%, Asian 56%, or Black 0.7%), cancer type, creatinine clearance 30 to 89 mL/min (estimated by the Cockcroft-Gault equation), mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST), or moderate hepatic (total bilirubin 1.5 to ≤ 3 ULN and any AST).

The effect of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR < 15 mL/min) with or without hemodialysis, and severe (total bilirubin > 3 ULN and any AST) hepatic impairment on zanidatamab-hrii pharmacokinetics is unknown.

12.6Immunogenicity The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies in the studies described below with the incidence of anti-drug antibodies in other studies, including those for zanidatamab-hrii or of other zanidatamab products. In patients who received ZIIHERA at the approved recommended dosages, 3.4% (18/534) of patients developed treatment-emergent anti-zanidatamab antibodies.

Of the patients who developed treatment-emergent anti-zanidatamab antibodies, 17% (3/18) also developed neutralizing antibodies. Because of the low occurrence of anti-drug antibodies, the effect of these antibodies on the pharmacokinetics, safety, and efficacy of zanidatamab products is unknown.

🧬 Mechanism of Action 81 words ▾

12.1Mechanism of Action Zanidatamab-hrii is a bispecific HER2-directed antibody that binds to extracellular domains 2 (ECD2) and 4 (ECD4) on HER2. Similar to other HER2-directed antibodies, in vitro binding of zanidatamab-hrii with HER2 causes clustering and results in internalization leading to a reduction of the receptor on the tumor cell surface. Zanidatamab-hrii induces complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP).

These mechanisms result in tumor growth inhibition and cell death in vitro and in vivo.

📦 How Supplied / Storage and Handling 61 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING ZIIHERA is supplied as a sterile, preservative free, white lyophilized powder in a single-dose vial. Each single-dose vial (NDC 68727‑950‑01) contains 300 mg zanidatamab‑hrii. Each carton of ZIIHERA (NDC 68727‑950‑02) contains 2 single-dose vials. Store in a refrigerator at 2°C to 8°C (36°F to 46°F) in the original carton until time of reconstitution. Do not freeze.

📋 Description 123 words ▾

11 DESCRIPTION Zanidatamab‑hrii is a humanized, IgG1-like, bispecific HER2-directed antibody. Zanidatamab‑hrii is produced in mammalian (Chinese hamster ovary) cell culture via recombinant DNA technology and has a molecular weight of 124.8 kDa. ZIIHERA (zanidatamab‑hrii) for injection is supplied as a sterile, preservative free, white lyophilized powder that requires reconstitution and dilution for intravenous use.

Each single-dose vial of reconstituted product contains 300 mg of zanidatamab‑hrii and the inactive ingredients: polysorbate 20 (0.63 mg), sodium succinate (4.3 mg), succinic acid (4.3 mg), and sucrose (567 mg). Following reconstitution with 5.7 mL Sterile Water for Injection, a solution containing 50 mg/mL zanidatamab‑hrii is produced with a deliverable volume of 6 mL, with pH of 4.6. The resulting solution is diluted and administered by intravenous infusion.

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Diarrhea Advise patients that ZIIHERA can cause severe diarrhea, and that prophylaxis with loperamide is required at treatment initiation when ZIIHERA is given with fluoropyrimidine- and platinum-containing chemotherapy for the treatment of GEA. Advise patients to notify their healthcare provider immediately if they experience new or worsening diarrhea, and to start loperamide with the first loose stool [see Warnings and Precautions ( 5.1 )] .

Embryo-Fetal Toxicity Advise female patients of the potential risk to a fetus. Advise female patients to contact their healthcare provider with a known or suspected pregnancy [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.1 )] . Advise females of reproductive potential to use effective contraception during treatment with ZIIHERA and for 4 months following the last dose [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.3 )].

Left Ventricular Dysfunction Advise patients that ZIIHERA can cause cardiac dysfunction and to contact a healthcare provider immediately for signs and symptoms of cardiac dysfunction [see Warnings and Precautions ( 5.3 )] . Infusion-Related Reactions Advise patients of the risk of infusion-related reactions and to inform a healthcare provider immediately for symptoms of an infusion-related reaction [see Warnings and Precautions ( 5.4 )] . Distributed by: Jazz Pharmaceuticals, Inc.

Palo Alto, CA 94306 Manufactured by: Jazz Pharmaceuticals Ireland Limited Fifth Floor, Waterloo Exchange Waterloo Road, Dublin 4 Dublin, Ireland D04 E5W7 U.S. License No. 2167

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE ZIIHERA ® (zye HAYR rah) (zanidatamab-hrii) for injection, for intravenous use What is the most important information I should know about ZIIHERA? ZIIHERA can cause serious side effects, including: • Diarrhea. Diarrhea during treatment with ZIIHERA can be severe, life threatening, and can lead to death.

Diarrhea may cause loss of fluids and body salts (electrolytes). To help prevent or reduce diarrhea during treatment with ZIIHERA, your healthcare provider: o will tell you to drink more fluids. o start you on an antidiarrheal medicine such as loperamide or other treatment, as needed. o may temporarily stop, reduce your dose or permanently stop treatment with ZIIHERA, or other medicines you take. If you get new or worsening diarrhea, tell your healthcare provider right away and take antidiarrheal medicine as prescribed.

Follow all of your healthcare providers instructions to help with your diarrhea. • Harm to your unborn baby. Taking ZIIHERA during pregnancy or within 4 months before pregnancy can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with ZIIHERA.

Females who are able to become pregnant: o Your healthcare provider should do a pregnancy test before you start treatment with ZIIHERA. o Use effective birth control (contraception) during treatment with ZIIHERA and for 4 months after the last dose. See “What are the possible side effects of ZIIHERA?” for more information about side effects. What is ZIIHERA?

ZIIHERA is a prescription medicine used to treat adults with: • gastroesophageal cancer (GEA) including gastric cancer, esophageal cancer, and gastroesophageal junction (GEJ) cancer. ZIIHERA is used in combination with fluoropyrimidine-and platinum- containing chemotherapy with or without tislelizumab-jsgr as the first treatment when your GEA: o cannot be removed by surgery or has spread to other parts of your body (metastatic) and o your tumor tests positive for human epidermal growth factor receptor 2 (HER2 IHC3+ or IHC 2+/ISH+). • biliary tract cancer (BTC) that includes cancer of the bile duct (cholangiocarcinoma) and cancer of the gallbladder.

ZIIHERA is used alone when your BTC: o cannot be removed by surgery or has spread to other parts of your body (metastatic), and o was previously treated, and o your tumor tests positive for human epidermal growth factor receptor 2 (HER2 IHC3+). Your healthcare provider will perform a test to make sure ZIIHERA is right for you. It is not known if ZIIHERA is safe and effective in children.

Before receiving ZIIHERA, tell your healthcare provider about all of your medical conditions, including if you: • have or have had any heart problems. • are breastfeeding or plan to breastfeed. It is not known if ZIIHERA passes into your breastmilk. Talk to your healthcare provider about the best way to feed your baby if you receive treatment with ZIIHERA.

Tell your healthcare provider about all the medicines you take , including prescription and over-the-counter medicines, vitamins, and herbal supplements. How should I receive ZIIHERA? • ZIIHERA is given through a vein by an intravenous (IV) infusion over 120 minutes for your first infusions. If you tolerate the first infusion well, your second infusion will be given to you over 90 minutes.

Each additional infusion may be given to you over 60 minutes. • ZIIHERA is given every 2 or 3 weeks. • Your healthcare provider: o will give you medicines 30 to 60 minutes before each treatment to help prevent infusion-related reactions or make them less severe o will give you diarrhea medicines during your first cycle of treatment, if you are being treated for GEA o may slow down your infusion, temporarily stop, or permanently stop your treatment with ZIIHERA if you have certain side effects o may do certain tests to check you for side effects o will decide how many treatments you need • If you miss a dose, call your healthcare provider as soon as possib… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~1 min read ▾

12.3Pharmacokinetics Zanidatamab-hrii pharmacokinetics were characterized at steady-state in patients with BTC and GEA at the approved recommended dosages and are presented as mean (coefficient of variation [CV]%) in Table 9. Table 9: Zanidatamab-hrii steady-state pharmacokinetics in patients with BTC and GEA at the approved recommended dosages Parameters ZIIHERA Dosage 1,800 mg /2,400 mg every 3 weeks in patients with GEA (%CV) 1,200 mg /1,600 mg every 2 weeks in patients with GEA (%CV) 20 mg/kg every 2 weeks in patients with BTC (%CV) C min (µg/mL) 176 (39%) 203 (36%) 200 (52%) C avg (µg/mL) 319 (27%) 319 (27%) 319 (36%) C max (µg/mL) 783 (20%) 609 (21%) 624 (26%) The C max of zanidatamab-hrii is dose proportional and the total systemic exposure (AUC) of zanidatamab-hrii is greater than dose proportional.

Steady state was approached after approximately 16 weeks following multiple doses. Zanidatamab-hrii median C trough accumulation is 1.8-fold. Distribution Zanidatamab-hrii volume of distribution is

8.1L (28.4%). Elimination Zanidatamab-hrii elimination half-life is 24 days with an apparent clearance (CL) of

0.3L/day (30%). Metabolism Zanidatamab‑hrii is expected to be metabolized into small peptides by catabolic pathways. Specific Populations No clinically meaningful differences in the pharmacokinetics of zanidatamab-hrii were observed based on age (22 to 87 years), sex, body weight (35 to 142 kg), race (White 39%, Asian 56%, or Black 0.7%), cancer type, creatinine clearance 30 to 89 mL/min (estimated by the Cockcroft-Gault equation), mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and AST > ULN or total bilirubin 1 to 1.5 times ULN and any AST), or moderate hepatic (total bilirubin 1.5 to ≤ 3 ULN and any AST).

The effect of severe renal impairment (eGFR 15 to 29 mL/min), end-stage renal disease (eGFR < 15 mL/min) with or without hemodialysis, and severe (total bilirubin > 3 ULN and any AST) hepatic impairment on zanidatamab-hrii pharmacokinetics is unknown.

🧬 Pharmacodynamics 40 words ▾

12.2Pharmacodynamics Zanidatamab-hrii exposure-response relationships for safety and efficacy and the time course of pharmacodynamic response have not been fully characterized. Cardiac Electrophysiology A mean increase in the QTc interval > 20 ms is unlikely at the approved recommended dosage.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1Gastroesophageal Adenocarcinoma (GEA) The efficacy of ZIIHERA in combination with fluoropyrimidine- and platinum-based chemotherapy, with or without tislelizumab-jsgr was evaluated for the treatment of GEA in HERIZON-GEA-01 (NCT05152147), a randomized, 3-arm, open-label, active-comparator, global trial in patients with advanced or metastatic HER2-positive GEA, including those with gastric, gastroesophageal junction, and esophageal adenocarcinoma. Eligible patients were those with untreated, unresectable locally advanced/metastatic GEA that was HER2-positive (IHC 3+ or IHC 2+/ISH+) per central testing, an Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0 or 1, and adequate organ function, including LVEF ≥ 50%.

Patients were enrolled regardless of their PD-L1 expression. Randomization was stratified by geographic region (Asia, EU/North America, or Rest of world), HER2 status per central assessment (3+ IHC staining, 2+ IHC staining with ISH-positivity), and ECOG PS (0, 1). Patients were randomized 1:1:1 to one of three treatment arms: • Arm A: Trastuzumab 8 mg/kg IV loading dose (Cycle 1 Day 1), and 6 mg/kg IV in subsequent cycles, followed by investigator’s choice of combination therapy of CAPOX or FP for at least 6 cycles. • Arm B: ZIIHERA 1,800 mg (weight < 70 kg) or 2,400 mg (body weight ≥ 70 kg) IV in combination with CAPOX or FP. • Arm C: ZIIHERA 1,800 mg (weight < 70 kg) or 2,400 mg (weight ≥ 70 kg) IV + tislelizumab-jsgr 200 mg IV in combination with CAPOX or FP.

CAPOX consisted of oxaliplatin 130 mg/m 2 intravenously and capecitabine 1,000 mg/m 2 orally for 14 days; FP consisted of cisplatin 80 mg/m 2 intravenously and fluorouracil 800 mg/m 2 /day intravenously for 5 days. All study medications, except oral capecitabine, were administered as an intravenous infusion every 3-week cycle. Treatment with ZIIHERA, with or without tislelizumab-jsgr continued in each arm until disease progression, unacceptable toxicity, or other discontinuation criteria were met.

The dual major efficacy outcome measures were progression-free survival (PFS) assessed by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and overall survival (OS). Additional efficacy outcome measures included Objective response rate (ORR) and Duration of Response (DOR) per BICR. A total of 914 GEA patients were randomized into HERIZON-GEA-01, including 638 patients with gastric adenocarcinoma, 195 patients with a gastroesophageal junction adenocarcinoma, and 81 patients with an esophageal adenocarcinoma.

The trial population characteristics were median age 63 years old (range: 21 to 87), 45% of patients were ≥ 65 years old; 79% were male; 55% were Asian, 39% were White, 1.9% were American Indian or Alaskan Native, and for 1.4% race was other or multiple; 84% were Non-Hispanic or Latino, 13% Hispanic/Latino, and for 3.2% ethnicity was unknown or not reported; 41% ECOG PS 0; and 59% ECOG PS 1. Eighty-three percent (83%) of patients had central HER2 IHC 3+ and 17% had central HER2 IHC 2+/ISH+. Eighty-nine percent (89%) of patients received CAPOX and 8.3% received FP.

ZIIHERA in combination with tislelizumab-jsgr and chemotherapy Efficacy results comparing Arm C and Arm A in the overall population are summarized in Table 10, Figure 1 and Figure 2. Statistically significant improvements in PFS and OS were demonstrated for the comparison of Arm C to Arm A. Table 10: Efficacy Results in HERIZON-GEA-01 Comparing Arm C and Arm A in the overall population Arm C ZIIHERA with chemotherapy and tislelizumab-jsgr N=302 Arm A Trastuzumab with chemotherapy N=308 Overall Survival Deaths (%) 134 (44%) 170 (55%) Median, months a 26.4 19.2 (95% CI) a (21.5, 30.3) (16.8, 21.8) Hazard ratio (95% CI) b 0.72 (0.57, 0.90) p-value c 0.0043 Progression-Free Survival Number of events (%) 154 (51%) 196 (64%) Median, months a 12.4 8.1 (95% CI) a (9.8, 18.5) (7.0, 8.9) Hazard ratio (95% CI)… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 31 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been conducted to evaluate the carcinogenic or mutagenic potential of zanidatamab‑hrii. Fertility studies with zanidatamab‑hrii have not been conducted.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 28 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Studies have not been conducted to evaluate the carcinogenic or mutagenic potential of zanidatamab‑hrii. Fertility studies with zanidatamab‑hrii have not been conducted.

📄 Recent Major Changes 34 words ▾

Boxed Warning 08/2026 Indications and Usage ( 1.1 ) 08/2026 Dosage and Administration ( 2.1 , 2.2 , 2.3 , 2.5 ) 08/2026 Warnings and Precautions ( 5.1 , 5.3 , 5.4 ) 08/2026

📄 Package Label / Principal Display Panel 11 words ▾

Package/Label Display Panel ZIIHERA Vial Label

Package/Label Display Panel ZIIHERA Carton

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

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 this package alone, 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.
📅 Q2 2025 – Q1 2026 · 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
12
Units reimbursed last 4 qtrs
7
Gross reimbursed last 4 qtrs
$26.4K
Avg / prescription
$2,196.59
Avg / unit
$3,761.82
Latest quarter Q1 2026
0Rx
Fee-for-service vs managed care ⓘ
100% FFS
Fee-for-service · 12 Rx Managed care · 0 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: no data reported NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 7 units · 0.0 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: no data reported LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
0.00.0
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 California 0.0 /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.

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 form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
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 Jazz Pharmaceuticals, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Jazz Pharmaceuticals, 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 J9276 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.
← 68727-0900-03 · Jazz 68743-0309-01 · Cosmo →
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.