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XGEVA denosumab 120 mg/1.7mL Injection, 1 vial — NDC 55513-0730-21 package photo

XGEVA denosumab 120 mg/1.7mL Injection, 1 vial

by Amgen, Inc · 1 VIAL, SINGLE-USE in 1 CARTON (55513-730-21) / 1.7 mL in 1 VIAL, SINGLE-USE
NDC 55513-0730-21
🏷️ FDA NDC (as labeled) 55513-730-21 billing pads the product segment with a zero
This package
Contains1 vial Cost per mL$2,001.52 NADAC Per package$3,402.58 / 1.7 ml Pack sizes2 compare ↓
Also comes in: 1.7 mL 55513-0730-01
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

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

⚠️
Other active recalls for Denosumab (different manufacturers) — 1 · tap to view
These affect other manufacturers’ products for the same ingredient — not necessarily the exact NDC on this page.
Class II · Apr 21, 2025 — CGMP Deviations; potential temperature excursions due to transit delays (Mckesson Medical-Surgical Inc. Corporate Office) · FDA recall D-0538-2025
Each entry is an official FDA enforcement report — look up any recall number in the FDA recall database ↗

🆔 Identity & classification

FDA NDC (as labeled) 55513-730-21
Product NDC 55513-730
11-digit billing NDC 55513073021
NCPDP billing unit ML — per mL (volume)
RxCUI 1046398, 1046402
UNII 4EQZ6YO2HI
UPC 0355513730013
Application # BLA125320
SPL Set ID 628f0998-1206-4001-aeee-18133aa9f3bf
Established class (EPC) RANK Ligand Inhibitor
Mechanism of action RANK Ligand Blocking Activity
DEA schedule Non-controlled
Marketing category BLA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2010-11-18
Route SUBCUTANEOUS
Dosage form INJECTION
Substance DENOSUMAB
GPI-14 30044530002030
GCN Seq No 066851
GCN 29261
HICL code 037012
Ingredient (HICL) Denosumab
HIC1 code P
Therapeutic class — broad (HIC1) Endocrine System
HIC2 code P4
Therapeutic class — intermediate (HIC2) Parathyroid/Bone Resorption Drugs
HIC3 code P4L
Therapeutic class — specific (HIC3) Bone Resorption Inhibitors
AHFS code 90:16.00.00
AHFS class Bone-Modifying Agents
FDB label name XGEVA 120 MG/1.7 ML VIAL
FDB brand name Xgeva
Legend status F — Federal legend — prescription drug or device
Biologic (Purple Book) 351(a)
Why two NDCs? The FDA registers this code as 55513-730-21 — 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 → 55513-0730-21. 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 RANK Ligand Inhibitor class.

Pharmacologic class RANK Ligand Inhibitor
Drug family (ATC) Other drugs affecting bone structure and mineralization
How it works RANK Ligand Blocking Activity
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

LabelerAmgen, Inc
FDA applicationBLA125320 (BLA)
Labeler code55513
First marketedNov 2010
Product typeHuman Prescription Drug
Portfolio81 products on file
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 XGEVA 120 MG/1.7 ML VIAL Ingredient Denosumab
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.

  • 0.17 mg / 1.7 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.
  • 1.8 mg / 1.7 mL UNII 4550K0SC9B
    Sodium acetate is a salt derived from acetic acid. It acts as a buffer to help maintain the medicine's pH stability and may serve as a preservative or solubilizer in liquid formulations.
  • UNII 55X04QC32I
    A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
  • 78.1 mg / 1.7 mL UNII 506T60A25R
    Sorbitol is a natural sugar alcohol derived from glucose. It serves as a sweetener, humectant, and bulking agent in medications to improve taste and help maintain moisture in the product.
  • UNII 059QF0KO0R
    Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.

5 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 systemPer mLPer package
Retail pharmacies payNADAC · weekly $2,001.520 $3,402.58 / 1.7 ml
Medicaid paysCMS SDUD · 12 mo No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · J0897 $30.101 / J0897 unit —
NADAC price history (per mL) — tap or hover for the price & month
Dec 2025 Jan 2026 $2,001.520 $1,943.220
▲ Up 3% over the last 2 months.
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)55513-730-21
11-digit billing NDC55513-0730-21
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeJ0897
DescriptorINJECTION, DENOSUMAB, 1 MG
Billing units / pkg70.59 units
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.

🔁 Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Xgeva 120 mg/1.7mLthis 55513-0730-21 Amgen, 1 vial $2,001.520 — Availability likely —
Wyost 120 mg/1.7mL 61314-0228-94 Sandoz 1 vial — — FDA listed —
Bilprevda 120 mg/1.7mL 78206-0195-01 Organon 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

🏛️
2010
First FDA approval
Jun 2010
📍
2026
Currently FDA-listed
16 years listed
🔓
2026
Biosimilars listed
18 FDA-licensed
🧬FDA-licensed biosimilars listed

18 interchangeables are FDA-licensed for this reference biologic — see the list below. (Biologics have no small-molecule generics.)

🛡️ Latest patent/protection date listed: Biosimilars are already FDA-licensed for this product — the last listed patent runs to Sep 2040.
📅 FDA approved Jun 1, 2010

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
Proliadenosumab Xgevadenosumab
Interchangeable 18
Aukelsodenosumab-kyqq Bildyosdenosumab-nxxp Bilprevdadenosumab-nxxp Bomyntradenosumab-bnht Boncresadenosumab-mobz Bosayadenosumab-kyqq Conexxencedenosumab-bnht Enobydenosumab-qbde Jubbontidenosumab-bbdz Jubereqdenosumab-desu Osenveltdenosumab-bmwo Ospomyvdenosumab-dssb Osvyrtidenosumab-desu Oziltusdenosumab-mobz Stoboclodenosumab-bmwo Wyostdenosumab-bbdz Xbrykdenosumab-dssb Xtrenbodenosumab-qbde
Source: FDA Purple Book (purplebooksearch.fda.gov), matched on the reference product’s active ingredient.
Patents & exclusivity — FDA Purple Book
US 10,583,397 — biologic patent
US 10,227,627 — biologic patent
US 10,822,630 — biologic patent
US 10,894,972 — biologic patent
US 11,077,404 — biologic patent
US 11,098,079 — biologic patent
US 11,130,980 — biologic patent
US 11,254,963 — biologic patent
US 11,299,760 — biologic patent
US 11,434,514 — biologic patent
US 8,053,236 — biologic patent
US 8,460,896 — biologic patent
US 8,680,248 — biologic patent
US 10,106,829 — biologic patent
US 10,513,723 — biologic patent
US 10,167,492 — biologic patent
US 9,481,901 — biologic patent
US 9,388,447 — biologic patent
US 9,359,435 — biologic patent
US 9,328,134 — biologic patent
US 9,320,816 — biologic patent
US 9,228,168 — biologic patent
US 9,133,493 — biologic patent
US 9,012,178 — biologic patent
US 8,058,418 — biologic patent
US 7,928,205 — biologic patent
US 7,427,659 — biologic patent
US 7,364,736 — biologic patent
US 11,685,772 — biologic patent
US 11,319,568 — biologic patent
US 11,275,090 — biologic patent
US 9,371,554 — biologic patent
US 12,025,618 — biologic patent
US 9,881,367 — biologic patent
US 9,803,166 — biologic patent
US 12,059,555 — biologic patent
US 11,492,372 — biologic patent
US 11,293,930 — biologic patent
US 11,192,919 — biologic patent
US 8,217,153 — biologic patent
US 12,084,686 — biologic patent
US 11,786,866 — biologic patent
US 11,744,950 — biologic patent
US 11,634,476 — biologic patent
US 7,662,930 — biologic patent
US 11,427,848 — biologic patent
US 11,459,595 — biologic patent
US 11,486,883 — biologic patent
US 11,946,085 — biologic patent
US 11,952,605 — biologic patent
US 7,888,101 — biologic patent
US 8,247,210 — biologic patent
US 10,421,987 — biologic patent
US 10,655,156 — biologic patent
US 10,907,186 — biologic patent
US 11,292,829 — biologic patent
US 11,384,378 — biologic patent
Exclusivity RefProduct
2010 2012 2014 2016 2018 2020 2022 2024 2026 2028 2030 2032 2034 2036 2038 2040
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.

Listed patents (57)
PatentTypeUse codeExpires
US 10,583,397 ↗ Biologic patent — Jul 28, 2035
US 10,227,627 ↗ Biologic patent — Dec 11, 2034
US 10,822,630 ↗ Biologic patent — Dec 1, 2035
US 10,894,972 ↗ Biologic patent — May 29, 2034
US 11,077,404 ↗ Biologic patent — May 13, 2035
US 11,098,079 ↗ Biologic patent — Jul 21, 2037
US 11,130,980 ↗ Biologic patent — Apr 5, 2035
US 11,254,963 ↗ Biologic patent — Dec 9, 2034
US 11,299,760 ↗ Biologic patent — Oct 30, 2034
US 11,434,514 ↗ Biologic patent — May 29, 2034
US 8,053,236 ↗ Biologic patent — Jan 19, 2030
US 8,460,896 ↗ Biologic patent — Dec 6, 2026
US 8,680,248 ↗ Biologic patent — Dec 6, 2026
US 10,106,829 ↗ Biologic patent — Dec 11, 2034
US 10,513,723 ↗ Biologic patent — Dec 9, 2034
US 10,167,492 ↗ Biologic patent — Dec 1, 2035
US 9,481,901 ↗ Biologic patent — May 29, 2034
US 9,388,447 ↗ Biologic patent — Apr 20, 2032
US 9,359,435 ↗ Biologic patent — May 22, 2027
US 9,328,134 ↗ Biologic patent — Feb 20, 2034
US 9,320,816 ↗ Biologic patent — Nov 14, 2030
US 9,228,168 ↗ Biologic patent — Jan 19, 2030
US 9,133,493 ↗ Biologic patent — Apr 20, 2032
US 9,012,178 ↗ Biologic patent — Aug 5, 2031
US 8,058,418 ↗ Biologic patent — Nov 30, 2023
US 7,928,205 ↗ Biologic patent — Feb 12, 2027
US 7,427,659 ↗ Biologic patent — Mar 15, 2025
US 7,364,736 ↗ Biologic patent — Feb 19, 2025
US 11,685,772 ↗ Biologic patent — Jun 29, 2032
US 11,319,568 ↗ Biologic patent — Mar 10, 2034
US 11,275,090 ↗ Biologic patent — Jul 2, 2037
US 9,371,554 ↗ Biologic patent — Dec 14, 2032
US 12,025,618 ↗ Biologic patent — Aug 26, 2039
US 9,881,367 ↗ Biologic patent — Aug 9, 2037
US 9,803,166 ↗ Biologic patent — Sep 29, 2034
US 12,059,555 ↗ Biologic patent — Sep 2, 2040
US 11,492,372 ↗ Biologic patent — Mar 11, 2034
US 11,293,930 ↗ Biologic patent — Mar 26, 2033
US 11,192,919 ↗ Biologic patent — Nov 13, 2035
US 8,217,153 ↗ Biologic patent — Jan 5, 2027
US 12,084,686 ↗ Biologic patent — Mar 10, 2034
US 11,786,866 ↗ Biologic patent — Oct 21, 2035
US 11,744,950 ↗ Biologic patent — Nov 21, 2039
US 11,634,476 ↗ Biologic patent — Jun 29, 2032
US 7,662,930 ↗ Biologic patent — Apr 24, 2027
US 11,427,848 ↗ Biologic patent — Jun 4, 2035
US 11,459,595 ↗ Biologic patent — Mar 10, 2034
US 11,486,883 ↗ Biologic patent — Mar 26, 2033
US 11,946,085 ↗ Biologic patent — May 29, 2034
US 11,952,605 ↗ Biologic patent — Mar 10, 2034
US 7,888,101 ↗ Biologic patent — Apr 6, 2027
US 8,247,210 ↗ Biologic patent — Dec 6, 2026
US 10,421,987 ↗ Biologic patent — May 29, 2034
US 10,655,156 ↗ Biologic patent — Dec 11, 2034
US 10,907,186 ↗ Biologic patent — Dec 11, 2034
US 11,292,829 ↗ Biologic patent — Jun 29, 2032
US 11,384,378 ↗ Biologic patent — Jun 4, 2035
FDA exclusivity
CodeWhat it grantsExpires
RefProductReference-product exclusivity (12-year, BPCIA) — no biosimilar can be licensed before this dateJun 1, 2022
Common questions
Is there a biosimilar for XGEVA 120 MG/1.7 ML VIAL?
Yes — at least one FDA-licensed biosimilar is listed for this biologic. See the Purple Book family above for the available products.
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 by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
1 vial55513-0730-01 22,711 Rx · $66,957,625
1 vial this page55513-0730-21 No Medicaid data
Drug total (last 4 qtrs): 22,711 Rx · 36,890 units · $66,957,625 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

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

Medicare Part D (outpatient prescription) spending for Xgeva — 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 Xgeva. 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
$9.8M
Claims incl. refills
2.9K
Beneficiaries
1.5K
Spend / beneficiary
$6,336.03
Spend / claim
$3,403.58
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.

📦 Packaging — all sizes for this product

Package NDCDescription Per unit Per pack Marketing startStatus
55513-0730-01 1 VIAL, SINGLE-USE in 1 CARTON (55513-730-01) / 1.7 mL in 1 VIAL, SINGLE-USE $2,001.52 / mL $3,402.58 2010-11-18 Active
55513-0730-21 You're viewing this 1 VIAL, SINGLE-USE in 1 CARTON (55513-730-21) / 1.7 mL in 1 VIAL, SINGLE-USE $2,001.52 / mL $3,402.58 2025-04-15 Active

This pack effectively ties for the lowest per-mL cost of the 2 priced pack sizes ($2,001.52 NADAC).

This pack shows little to no recent Medicaid volume — a different pack size carries most fills. See all packs ↓

Pack size FAQ

What quantity is in NDC 55513-0730-21?
NDC 55513-0730-21 contains 1 vial — 1 vial, single-use in 1 carton / 1.7 ml in 1 vial, single-use.
What is the difference between NDC 55513-0730-21 and NDC 55513-0730-01?
Both are XGEVA denosumab 120 mg/1.7mL Injection — the drug itself is identical. NDC 55513-0730-21 is the 1 vial package, while NDC 55513-0730-01 is the 1 vial package.
What NDC number is used to bill for this package of XGEVA denosumab 120 mg/1.7mL Injection?
Bill NDC 55513-0730-21 — the 11-digit billing format is 55513073021. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.

📄 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.
🎯 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 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients
🎯 Indications and Usage 173 words ▾

1 INDICATIONS AND USAGE Xgeva is a RANK ligand (RANKL) inhibitor indicated for: Prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors. ( 1.1 ) Treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity. ( 1.2 , 14.3 ) Treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

( 1.3 )

1.1Multiple Myeloma and Bone Metastasis from Solid Tumors Xgeva is indicated for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors.

1.2Giant Cell Tumor of Bone Xgeva is indicated for the treatment of adults and skeletally mature adolescents with giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity [see Clinical Trials ( 14.2 )] .

1.3Hypercalcemia of Malignancy Xgeva is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy.

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION Xgeva should be administered by a healthcare provider. ( 2.1 ) Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally. ( 2.1 ) Multiple Myeloma and Bone Metastasis from Solid Tumors: Administer 120 mg every 4 weeks as a subcutaneous injection in the upper arm, upper thigh, or abdomen.

( 2.2 ) Giant Cell Tumor of Bone: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.3 ) Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia.

( 2.2 , 2.3 ) Hypercalcemia of Malignancy: Administer 120 mg every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. ( 2.4 )

2.1Important Administration Instructions Xgeva should be administered by a healthcare provider. Xgeva is intended for subcutaneous route only and should not be administered intravenously, intramuscularly, or intradermally.

2.2Multiple Myeloma and Bone Metastasis from Solid Tumors The recommended dose of Xgeva is 120 mg administered as a subcutaneous injection every 4 weeks in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions ( 5.3 )].

2.3Giant Cell Tumor of Bone The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen. Administer calcium and vitamin D as necessary to treat or prevent hypocalcemia [see Warnings and Precautions ( 5.3 )].

2.4Hypercalcemia of Malignancy The recommended dose of Xgeva is 120 mg administered every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy. Administer subcutaneously in the upper arm, upper thigh, or abdomen.

2.5Preparation and Administration Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Xgeva is a clear, colorless to pale yellow solution that may contain trace amounts of translucent to white proteinaceous particles. Do not use if the solution is discolored or cloudy or if the solution contains many particles or foreign particulate matter.

Prior to administration, Xgeva may be removed from the refrigerator and brought to room temperature up to 25°C (77°F) by standing in the original container. This generally takes 15 to 30 minutes. Do not warm Xgeva in any other way [see How Supplied/Storage and Handling ( 16 )].

Use a 27-gauge needle to withdraw and inject the entire contents of the vial. Do not re-enter the vial. Discard vial after single entry.

💊 Dosage Forms and Strengths 35 words ▾

3 DOSAGE FORMS AND STRENGTHS Injection: 120 mg/1.7 mL (70 mg/mL) clear, colorless to pale yellow solution in a single-dose vial. Injection: 120 mg/1.7 mL (70 mg/mL) solution in a single-dose vial ( 3 )

⛔ Contraindications 71 words ▾

4 CONTRAINDICATIONS Hypocalcemia ( 4.1 ) Known clinically significant hypersensitivity to Xgeva or denosumab products ( 4.2 )

4.1Hypocalcemia Pre-existing hypocalcemia must be corrected prior to initiating therapy with Xgeva [s ee Warnings and Precautions ( 5.3 )] .

4.2Hypersensitivity Xgeva is contraindicated in patients with known clinically significant hypersensitivity to Xgeva or denosumab products [see Warnings and Precautions ( 5.2 ) and Adverse Reactions ( 6.2 )] .

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS Drug Products with Same Active Ingredient: Patients receiving Xgeva should not receive other denosumab products concomitantly. ( 5.1 ) Hypersensitivity reactions including anaphylaxis may occur. Discontinue permanently if a clinically significant reaction occurs.

( 5.2 ) Hypocalcemia: Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct hypocalcemia prior to initiating Xgeva. Monitor calcium levels during therapy, especially in the first weeks of initiating therapy, and adequately supplement all patients with calcium and vitamin D.

( 5.3 ) Osteonecrosis of the jaw (ONJ) has been reported in patients receiving Xgeva. Perform an oral examination prior to starting Xgeva. Monitor for symptoms.

Avoid invasive dental procedures during treatment with Xgeva. ( 5.4 ) Atypical femoral fracture: Evaluate patients with thigh or groin pain to rule out a femoral fracture. ( 5.5 ) Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone and in Patients with Growing Skeletons: Monitor patients for signs and symptoms of hypercalcemia, and manage as clinically appropriate.

( 5.6 , 8.4 ) Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation: When Xgeva treatment is discontinued, evaluate the individual patient’s risk for vertebral fractures. ( 5.7 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of potential risk to the fetus and to use effective contraception.

( 5.8 , 8.1 , 8.3 )

5.1Drug Products with Same Active Ingredient Patients receiving Xgeva should not receive other denosumab products concomitantly.

5.2Hypersensitivity Clinically significant hypersensitivity including anaphylaxis has been reported with use of Xgeva. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue Xgeva therapy permanently [s ee Contraindi cation s ( 4.2 ) and Adverse Reactions ( 6.2 )] .

5.3Hypocalcemia Xgeva can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to Xgeva treatment. Monitor calcium levels, throughout Xgeva therapy, especially in the first weeks of initiating therapy, and administer calcium, magnesium, and vitamin D as necessary.

Concomitant use of calcimimetics and other drugs that can lower calcium levels may worsen hypocalcemia risk and serum calcium should be closely monitored. Advise patients to contact a healthcare provider for symptoms of hypocalcemia [see Contraindications ( 4.1 ), Adverse Reactions ( 6.1 , 6.2 ) , and Patient Counseling Information ( 17 )]. An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/min and/or on dialysis), and with inadequate/no calcium supplementation.

Monitor calcium levels and calcium and vitamin D intake [see Adverse Reactions ( 6.1 ), Use in Specific Populations ( 8.6 ), and Clinical Pharmacology ( 12.3 )] .

5.4Osteonecrosis of the Jaw (ONJ) Osteonecrosis of the jaw (ONJ) has been reported in patients receiving Xgeva, manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with cancer, the incidence of ONJ was higher with longer duration of exposure [see Adverse Reactions ( 6.1 )].

Seventy-nine percent of patients with ONJ had a history of tooth extraction, poor oral hygiene, or use of a dental appliance as a predisposing factor. Other risk factors for the development of ONJ include immunosuppressive therapy, treatment with angiogenesis inhibitors…

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following adverse reactions are discussed below and elsewhere in the labeling: • Hypersensitivity [see Warnings and Precautions ( 5.2 )] • Hypocalcemia [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 ) ] • Osteonecrosis of the Jaw [see Warnings and Precautions ( 5.4 )] • Atypical Subtrochanteric and Diaphyseal Femoral Fracture [see Warnings and Precautions ( 5.5 )] • Hypercalcemia following treatment discontinuation in patients with giant cell tumor of bone and in patients with growing skeletons [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.4 ) ] • Multiple vertebral fractures (MVF) following treatment discontinuation [see Warnings and Precautions ( 5.7 )] Bone Metastasis from Solid Tumors: Most common adverse reactions (≥ 25%) were fatigue/asthenia, hypophosphatemia, and nausea.

( 6.1 ) Multiple Myeloma: Most common adverse reactions (≥ 10%) were diarrhea, nausea, anemia, back pain, thrombocytopenia, peripheral edema, hypocalcemia, upper respiratory tract infection, rash, and headache. ( 6.1 ) Giant Cell Tumor of Bone: Most common adverse reactions (≥ 10%) were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. ( 6.1 ) Hypercalcemia of Malignancy: Most common adverse reactions (> 20%) were nausea, dyspnea, decreased appetite, headache, peripheral edema, vomiting, anemia, constipation, and diarrhea.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) 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. Bone Metastasis from Solid Tumors The safety of Xgeva was evaluated in three randomized, double-blind, double-dummy trials [see Clinical Trials ( 14.1 )] in which a total of 2841 patients with bone metastasis from prostate cancer, breast cancer, or other solid tumors, or lytic bony lesions from multiple myeloma received at least one dose of Xgeva.

In Studies 20050136, 20050244, and 20050103, patients were randomized to receive either 120 mg of Xgeva every 4 weeks as a subcutaneous injection or 4 mg (dose adjusted for reduced renal function) of zoledronic acid every 4 weeks by intravenous (IV) infusion. Entry criteria included serum calcium (corrected) from 8 to 11.5 mg/dL (2 to 2.9 mmol/L) and creatinine clearance 30 mL/min or greater. Patients who had received IV bisphosphonates were excluded, as were patients with prior history of ONJ or osteomyelitis of the jaw, an active dental or jaw condition requiring oral surgery, non-healed dental/oral surgery, or any planned invasive dental procedure.

During the study, serum chemistries including calcium and phosphorus were monitored every 4 weeks. Calcium and vitamin D supplementation was recommended but not required. The median duration of exposure to Xgeva was 12 months (range: 0.1-41) and median duration on-study was 13 months (range: 0.1-41).

Of patients who received Xgeva, 46% were female. Eighty-five percent were White, 5% Hispanic/Latino, 6% Asian, and 3% Black. The median age was 63 years (range: 18-93).

Seventy-five percent of patients who received Xgeva received concomitant chemotherapy. The most common adverse reactions in patients (incidence greater than or equal to 25%) were fatigue/asthenia, hypophosphatemia, and nausea (see Table 1). The most common serious adverse reaction was dyspnea.

The most common adverse reactions resulting in discontinuation of Xgeva were osteonecrosis and hypocalcemia. Table 1. Selected Adverse reactions reported in at least 10% of patients receiving Xgeva in Studies 20050136, 20050244, and 20050103, and meeting one of the following criteria: At least 1% greater incidence in Xgeva-treated patients, or Between-g…

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pediatric patients: Recommended only for treatment of skeletally mature adolescents with giant cell tumor of bone. ( 8.4 ) Renal impairment: Patients with creatinine clearance less than 30 mL/min or receiving dialysis are at risk for hypocalcemia. Adequately supplement with calcium and vitamin D. ( 8.6 )

8.1Pregnancy Risk Summary Based on findings in animals and its mechanism of action, Xgeva can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are insufficient data with denosumab use in pregnant women to inform any drug associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 25-fold higher than the recommended human dose of Xgeva based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality; and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [ see Data ] .

Apprise pregnant women of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data Animal Data The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”). In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 25-fold higher than the recommended human dose of Xgeva based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality.

Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal.

There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated.

Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero ; however, development and lactation have not been fully evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.2 )] .

8.2Lactation Risk Summary There is no information regarding the presence of Xgeva (denosumab) in human milk, the effects on the breastfed child, or the effects on milk production. Denosumab was detected in the maternal milk of cynomolgus monkeys up to 1 month after the last dose of denosumab (≤ 0.5% milk:serum ratio) and maternal mammary gland development was normal, with no impaired lactation. However, pregnant RANKL knockout mice showed altered maturation of the…

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary Based on findings in animals and its mechanism of action, Xgeva can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are insufficient data with denosumab use in pregnant women to inform any drug associated risks for adverse developmental outcomes. In utero denosumab exposure from cynomolgus monkeys dosed monthly with denosumab throughout pregnancy at a dose 25-fold higher than the recommended human dose of Xgeva based on body weight resulted in increased fetal loss, stillbirths, and postnatal mortality; and absent lymph nodes, abnormal bone growth, and decreased neonatal growth [ see Data ] .

Apprise pregnant women of the potential risk to the fetus. The background rate of major birth defects and miscarriage is unknown for the indicated population. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data Animal Data The effects of denosumab on prenatal development have been studied in both cynomolgus monkeys and genetically engineered mice in which RANK ligand (RANKL) expression was turned off by gene removal (a “knockout mouse”). In cynomolgus monkeys dosed subcutaneously with denosumab throughout pregnancy starting at gestational day 20 and at a pharmacologically active dose 25-fold higher than the recommended human dose of Xgeva based on body weight, there was increased fetal loss during gestation, stillbirths, and postnatal mortality.

Other findings in offspring included absence of axillary, inguinal, mandibular, and mesenteric lymph nodes; abnormal bone growth, reduced bone strength, reduced hematopoiesis, dental dysplasia, and tooth malalignment; and decreased neonatal growth. At birth out to one month of age, infants had measurable blood levels of denosumab (22-621% of maternal levels). Following a recovery period from birth out to 6 months of age, the effects on bone quality and strength returned to normal; there were no adverse effects on tooth eruption, though dental dysplasia was still apparent; axillary and inguinal lymph nodes remained absent, while mandibular and mesenteric lymph nodes were present, though small; and minimal to moderate mineralization in multiple tissues was seen in one recovery animal.

There was no evidence of maternal harm prior to labor; adverse maternal effects occurred infrequently during labor. Maternal mammary gland development was normal. There was no fetal NOAEL (no observable adverse effect level) established for this study because only one dose of 50 mg/kg was evaluated.

Mammary gland histopathology at 6 months of age was normal in female offspring exposed to denosumab in utero ; however, development and lactation have not been fully evaluated. In RANKL knockout mice, absence of RANKL (the target of denosumab) also caused fetal lymph node agenesis and led to postnatal impairment of dentition and bone growth. Pregnant RANKL knockout mice showed altered maturation of the maternal mammary gland, leading to impaired lactation [see Use in Specific Populations ( 8.3 ) and Nonclinical Toxicology ( 13.2 )] .

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use The safety and efficacy of Xgeva have not been established in pediatric patients except in skeletally mature adolescents (aged 12–16 years) with giant cell tumor of bone. Xgeva is recommended only for treatment of skeletally mature adolescents (aged 12–16 years) with giant cell tumor of bone [see Indications and Usage ( 1.2 )] . Clinically significant hypercalcemia after treatment discontinuation has been reported in pediatric patients with growing skeletons who received denosumab for giant cell tumor of bone or for unapproved indications [see Adverse Reactions ( 6.2 ) and Warnings and Precautions ( 5.6 )].

Xgeva was studied in an open-label trial that enrolled a subset of 19 adolescent patients (aged 12-16 years) with giant cell tumor of bone who had reached skeletal maturity, defined by at least 1 mature long bone (e.g., closed epiphyseal growth plate of the humerus), and had a body weight ≥ 45 kg [see Indications and Usage ( 1.2 ) and Clinical Trials ( 14.3 )]. A total of one of five (20%) evaluable adolescent patients had an objective response by retrospective independent assessment of radiographic response according to modified Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

The adverse reaction profile and efficacy results appeared to be similar in skeletally mature adolescents and adults [see Adverse Reactions ( 6.1 ) and Clinical Trials ( 14.3 )] . Animal Data Treatment with Xgeva may impair bone growth in children with open growth plates and may inhibit eruption of dentition. In neonatal rats, inhibition of RANKL (the target of Xgeva therapy) with a construct of osteoprotegerin bound to Fc (OPG-Fc) at doses ≤ 10 mg/kg was associated with inhibition of bone growth and tooth eruption.

Adolescent primates treated with denosumab at doses 5 and 25 times (10 and 50 mg/kg dose) higher than the recommended human dose of 120 mg administered once every 4 weeks, based on body weight (mg/kg), had abnormal growth plates, considered to be consistent with the pharmacological activity of denosumab. Cynomolgus monkeys exposed in utero to denosumab exhibited bone abnormalities, reduced hematopoiesis, tooth malalignment, decreased neonatal growth, and an absence of axillary, inguinal, mandibular, and mesenteric lymph nodes.

Some bone abnormalities recovered once exposure was ceased following birth; however, axillary and inguinal lymph nodes remained absent 6 months post-birth [see Use in Specific Populations ( 8.1 ) ] .

🧓 Geriatric Use 81 words ▾

8.5Geriatric Use Of the total number of patients in clinical studies that received Xgeva (n = 2841) in Studies 20050136, 20050244, and 20050103, 1271 (44%) were ≥ 65 years old, while 473 patients (17%) were ≥ 75 years old. Of the 859 patients in Study 20090482 that received Xgeva, 387 patients (45%) were ≥ 65 years old, while 141 patients (16%) were ≥ 75 years old. No overall differences in safety or efficacy were observed between older and younger patients.

🆘 Overdosage 10 words ▾

10 OVERDOSAGE There is no experience with overdosage of Xgeva.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Xgeva binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. Increased osteoclast activity, stimulated by RANKL, is a mediator of bone pathology in solid tumors with osseous metastases. Similarly, giant cell tumors of bone consist of stromal cells expressing RANKL and osteoclast-like giant cells expressing RANK receptor, and signaling through the RANK receptor contributes to osteolysis and tumor growth.

Xgeva prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts, their precursors, and osteoclast-like giant cells.

12.2Pharmacodynamics In patients with breast cancer and bone metastases, the median reduction in uNTx/Cr was 82% within 1 week following initiation of Xgeva 120 mg administered subcutaneously. In Studies 20050136, 20050244, and 20050103, the median reduction in uNTx/Cr from baseline to Month 3 was approximately 80% in 2075 Xgeva-treated patients. In a phase 3 study of patients with newly diagnosed multiple myeloma who received subcutaneous doses of Xgeva 120 mg every 4 weeks (Q4W), median reductions in uNTx/Cr of approximately 75% were observed by Week 5.

Reductions in bone turnover markers were maintained, with median reductions of 74% to 79% for uNTx/Cr from weeks 9 to 49 of continued 120 mg Q4W dosing. In adult and skeletally mature adolescent patients with giant cell tumor of bone who received subcutaneous doses of Xgeva 120 mg Q4W with a 120 mg loading dose on Days 8 and 15, median reductions in uNTx/Cr from baseline were 84% at Week 13 and 82% at Week 25.

12.3Pharmacokinetics Following subcutaneous administration, bioavailability was 62%. Denosumab displayed nonlinear pharmacokinetics at doses below 60 mg, but approximately dose-proportional increases in exposure at higher doses. With multiple subcutaneous doses of 120 mg once every 4 weeks, up to 2.8-fold accumulation in serum denosumab concentrations was observed and steady-state was achieved by 6 months.

A mean (± standard deviation) serum steady-state trough concentration of 20.5 (± 13.5) mcg/mL was achieved by 6 months. The mean elimination half-life was 28 days. In patients with newly diagnosed multiple myeloma who received 120 mg every 4 weeks, denosumab concentrations appear to reach steady-state by Month 6.

In patients with giant cell tumor of bone, after administration of subcutaneous doses of 120 mg once every 4 weeks with additional 120 mg doses on Days 8 and 15 of the first month of therapy, mean (± standard deviation) serum trough concentrations on Day 8, 15, and one month after the first dose were 19.0 (± 24.1), 31.6 (± 27.3), 36.4 (± 20.6) mcg/mL, respectively. Steady-state was achieved in 3 months after initiation of treatment with a mean serum trough concentration of 23.4 (± 12.1) mcg/mL. Speci al Populations Body Weight: A population pharmacokinetic analysis was performed to evaluate the effects of demographic characteristics.

Denosumab clearance and volume of distribution were proportional to body weight. The steady-state exposure following repeat subcutaneous administration of 120 mg every 4 weeks to 45 kg and 120 kg subjects were, respectively, 48% higher and 46% lower than exposure of the typical 66 kg subject. Age, Gender and Race: The pharmacokinetics of denosumab was not affected by age, gender, and race.

Pediatrics: In skeletally-mature adolescent patients (12 to 16 years of age) with giant cell tumor of bone (GCTB) who received 120 mg every 4 weeks with a 120 mg loading dose on Days 8 and 15, the pharmacokinetics of denosumab were comparable to those observed in adult patients with GCTB. Hepatic Impairment: No clinical trials have been conducted to evaluate the effect of hepatic impairment on the pharmacokinetics of denosumab. Renal Impairment: In clinical trials of 87 patients with varying degrees of renal…

🧬 Mechanism of Action 102 words ▾

12.1Mechanism of Action Xgeva binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. Increased osteoclast activity, stimulated by RANKL, is a mediator of bone pathology in solid tumors with osseous metastases. Similarly, giant cell tumors of bone consist of stromal cells expressing RANKL and osteoclast-like giant cells expressing RANK receptor, and signaling through the RANK receptor contributes to osteolysis and tumor growth.

Xgeva prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts, their precursors, and osteoclast-like giant cells.

📦 How Supplied / Storage and Handling 129 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Xgeva (denosumab) injection is a clear, colorless to pale yellow solution supplied in a single-dose vial. 120 mg/1.7 mL (70 mg/mL) 1 vial per carton NDC 55513-730-01 NDC 55513-730-21 Store Xgeva refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze.

Prior to administration, Xgeva may be allowed to reach room temperature up to 25°C (77°F) in the original container. Once removed from the refrigerator, Xgeva must not be exposed to temperatures above 25°C (77°F) and must be used within 30 days. Discard Xgeva if not used within the 30 days.

Do not use Xgeva after the expiry date printed on the label. Protect Xgeva from direct light and heat. Avoid vigorous shaking of Xgeva.

📋 Description 83 words ▾

11 DESCRIPTION Denosumab is a human IgG2 monoclonal antibody that binds to human RANKL. Denosumab has an approximate molecular weight of 147 kDa and is produced in genetically engineered mammalian (Chinese hamster ovary) cells. Xgeva (denosumab) injection is a sterile, preservative-free, clear, colorless to pale yellow solution.

Each single-dose vial contains 1.7 mL solution of 120 mg denosumab, glacial acetic acid (1.8 mg), polysorbate 20 (0.17 mg), sorbitol (78.1 mg), Water for Injection (USP), and sodium hydroxide to adjust the pH to 5.2.

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION Drug Products with Same Active Ingredient Advise patients that if they receive Xgeva, they should not receive other denosumab products concomitantly [see Warnings and Precautions ( 5.1 )]. Hypersensitivity Advise patients to seek prompt medical attention if signs or symptoms of hypersensitivity reactions occur. Advise patients who have had signs or symptoms of systemic hypersensitivity reactions that they should not receive denosumab products [see Warnings and Precautions ( 5.2 ) and Contraindications ( 4.2 )] .

Hypocalcemia Adequately supplement patients with calcium and vitamin D and instruct them on the importance of maintaining serum calcium levels while receiving Xgeva [see Warnings and Precautions ( 5.3 ) and Use in Specific Populations ( 8.6 )] . Advise patients to seek prompt medical attention if they develop signs or symptoms of hypocalcemia. Osteonecrosis of the Jaw Advise patients to maintain good oral hygiene during treatment with Xgeva and to inform their dentist prior to dental procedures that they are receiving Xgeva.

Patients should avoid invasive dental procedures during treatment with Xgeva and inform their healthcare provider or dentist if they experience persistent pain and/or slow healing of the mouth or jaw after dental surgery [see Warnings and Precautions ( 5.4 )] . Atypical Subtrochanteric and Diaphyseal Femoral Fracture Advise patients to report new or unusual thigh, hip, or groin pain [see Warnings and Precautions ( 5.5 )] . Hypercalcemia Following Treatment Discontinuation in Patients with Giant Cell Tumor of Bone and in Patients with Growing Skeletons Advise patients to report nausea, vomiting, headache, and decreased alertness following treatment discontinuation [see Warnings and Precautions ( 5.6 ) and Use in Specific Populations ( 8.4 ) ].

Multiple Vertebral Fractures (MVF) Following Treatment Discontinuation Advise patients that after treatment with Xgeva is stopped there may be an increased risk of having broken bones in the spine especially in patients who have had a fracture or who have had osteoporosis. Advise patients not to interrupt Xgeva therapy without their physician’s advice [see Warnings and Precautions ( 5.7 )] . Embryo-Fetal Toxicity Advise females of reproductive potential that Xgeva can cause harm to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.8 ) and Use in Specific Populations ( 8.1 , 8.3 )] .

Advise females of reproductive potential to use effective contraception during treatment and for at least 5 months after the last dose of Xgeva [ see Use in Specific Populations ( 8.3 ) ] . Xgeva ® (denosumab) Manufactured by: Amgen Inc. One Amgen Center Drive Thousand Oaks, California 91320-1799 U.S.

License No. 1080 Patent: http://pat.amgen.com/xgeva/ © 2010-2020, 2025-2026 Amgen Inc. All rights reserved.

1xxxxx – v24

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗
← 55513-0710-01 · Amgen, 55513-0740-10 · Amgen, →
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