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Gadobutrol 604.72 mg/mL Injection — NDC 65219-0289-65 package photo
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Gadobutrol 604.72 mg/mL Injection — NDC 65219-289-65 (Billing 65219-0289-65)

by Fresenius Kabi USA, LLC · 10 BOTTLE in 1 CARTON / 65 mL in 1 BOTTLE

This is a package of Gadobutrol 604.72 mg/mL Injection from Fresenius Kabi USA, LLC, marketed since Oct 2023 and currently FDA-listed. It is this product's only package size.

NDC 65219-0289-65
🏷️ FDA NDC (as labeled) 65219-289-65 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

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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 65219-289-65 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
65219 labeler · 289 product · 65 package
Package marketed since
Oct 1, 2023
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Barcode (UPC-A, from the NDC)
3 6521928965 4
Medicaid fills, this package
13 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 65219-289-65
Product NDC 65219-289
11-digit billing NDC 65219028965
NCPDP billing unit ML — per mL (volume)
UNII 1BJ477IO2L
Application # ANDA216081
SPL Set ID c0dd1618-0bb3-4974-846b-e5afc2311ae6
Established class (EPC) Gadolinium-based Contrast Agent
Mechanism of action Magnetic Resonance Contrast Activity
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-10-01
Route INTRAVENOUS
Dosage form INJECTION
Substance GADOBUTROL

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

GCN Seq No 054612
GCN 22586
HICL code 021847
Ingredient (HICL) Gadobutrol
HIC1 code Z
Therapeutic class — broad (HIC1) Body As A Whole
HIC2 code Z9
Therapeutic class — intermediate (HIC2) Unclassified Drugs
HIC3 code Z9D
Therapeutic class — specific (HIC3) Diagnostic Preparations,Miscellaneous
AHFS code 36:68.00.00
AHFS class Roentgenography And Other Imaging Agents
FDB label name GADOBUTROL 65MMOL/65ML BULK VL
FDB brand name Gadobutrol
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 054612
  • GCN: 22586
  • HICL (First Databank): 021847
  • AHFS class code: 36:68.00.00
Why two NDCs? The FDA registers this code as 65219-289-65 — 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 → 65219-0289-65. 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.

Clinical

Label name GADOBUTROL 65MMOL/65ML BULK VL Ingredient Gadobutrol
📗 Our plain-language guide HelloPharmacist
  • It is a contrast dye that makes your MRI pictures clearer. It is used for scans of the brain and spine, breast, blood vessels and heart. It does not treat a condition. It helps you...
  • A healthcare professional injects it into a vein, usually followed by a saline flush. The amount is based on your weight. You do not take it at home.
  • Most people have none. When they do occur, they are usually mild, such as headache, nausea, dizziness, an odd taste or feeling warm. Let your care team know if anything bothers you...
  • Get help right away for trouble breathing, swelling of the face or throat, hives or fainting. Allergic reactions can sometimes show up days later. Also call if your skin thickens o...
📖 Read our full Gadobutrol 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 eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $2.68 $26.77 / 10 bottles
Medicare drug plans payPart D · quarterly No Part D plan price is available for this NDC in our data.
Medicare Part B allowsASP · A9585 $0.262 / A9585 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)65219-289-65
11-digit billing NDC65219-0289-65
Format5-3-2 as registered → padded to 5-4-2 for billing (zero added to the product segment)
HCPCS J-codeA9585
Descriptor0.1 ML
Billing units / pkg6,500 units
How the units are derivedThis package is 65; the HCPCS unit is 0.1 ML, so one package = 6500 billing units.
Medicare Part B spend (2026 (Q1))$1,462,309 · 65,285 claims · $22.40 per claim (all NDCs under A9585)
Crosswalk sourceCMS ASP NDC-HCPCS Crosswalk
Where does this data come from?
The HCPCS J-code crosswalk comes from the CMS ASP NDC-HCPCS crosswalk and the DMEPDAC (DME MAC) NDC-HCPCS crosswalk — free public CMS data. Billing units are derived from the code’s descriptor and the package amount.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
65219-0289-65 You're viewing this Main listing 10 BOTTLE in 1 CARTON / 65 mL in 1 BOTTLE 2023-10-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Gadobutrol 604.72 mg/mL 65219-0287-30 Fresenius 10 bottles — — FDA listed —
gadobutrol 604.72 mg/mL 70436-0217-80 Slate 1 vial — AP FDA listed —
Gadavist 604.72 mg/mL 50419-0325-14 Bayer 5 bottles — AP Discontinued —
gadobutrol 604.72 mg/mL 70436-0214-54 Slate 20 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70436-0213-82 Slate 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70436-0218-84 Slate 3 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70436-0212-54 Slate 20 vials — AP FDA listed —
Gadobutrol 604.72 mg/mLthis 65219-0289-65 Fresenius 10 bottles — — FDA listed —
gadobutrol 604.72 mg/mL 70436-0216-81 Slate 5 vials — AP FDA listed —
Gadobutrol 604.72 mg/mL 65219-0281-02 Fresenius 3 vials — — FDA listed —
gadobutrol 604.72 mg/mL 42337-0007-02 Viwit 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70710-2066-06 Zydus 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 42337-0005-02 Viwit 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70710-2064-06 Zydus 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 70710-2065-06 Zydus 10 vials — AP FDA listed —
gadobutrol 604.72 mg/mL 42337-0006-02 Viwit 10 vials — AP FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
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 & generic status

🏛️
2023
On the market since
Oct 2023
📍
2026
Currently FDA-listed
3 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

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

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

  • UNII PO5286589K
    A synthetic compound used as a preservative and antimicrobial agent in medicines. It helps prevent bacterial and fungal growth, extending the product's shelf life and maintaining stability.
  • UNII QTT17582CB
    A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
  • UNII 023C2WHX2V
    Tromethamine is a chemical buffer that helps maintain the proper acidity level in liquid medicines. It neutralizes acids and stabilizes the solution so the medication remains effective and safe throughout its shelf life.
  • 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.

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

LabelerFresenius Kabi USA, LLC
Application holderJIANGSU HENGRUI PHARMACEUTICALS CO LTD
FDA applicationANDA216081 (ANDA)
Labeler code65219
First marketedOct 2023
Product typeHuman Prescription Drug
Portfolio554 products on file

More NDCs from Fresenius Kabi USA, LLC labeler code 65219

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 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 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 ~2 min read ▾

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS Risk Associated with Intrathecal Use Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadobutrol injection is not approved for intrathecal use [see Warnings and Precautions ( 5.1 )]. Nephrogenic Systemic Fibrosis GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of drugs.

Avoid use of gadobutrol injection in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. • The risk for NSF appears highest among patients with: o Chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ), or o Acute kidney injury. • Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age > 60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing. • For patients at highest risk for NSF, do not exceed the recommended gadobutrol dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration [see Warnings and Precautions ( 5.2 )].

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC FIBROSIS See full prescribing information for complete boxed warning • Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadobutrol injection is not approved for intrathecal use ( 5.1 ) • GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of gadobutrol injection in these patients unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities.

The risk for NSF appears highest among patients with: Screen patients for acute kidney injury and other conditions that may reduce renal function. For patients at risk for chronically reduced renal function (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing ( 5.2 ). o Chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ), or o Acute kidney injury. Screen patients for acute kidney injury and other conditions that may reduce renal function.

For patients at risk for chronically reduced renal function (for example, age >60 years, hypertension or diabetes), estimate the glomerular filtration rate (GFR) through laboratory testing ( 5.2 )

🎯 Indications and Usage ~1 min read ▾

1 INDICATIONS AND USAGE Gadobutrol injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI): • To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients (including term neonates) ( 1.1 ) • To assess the presence and extent of malignant breast disease in adult patients ( 1.2 ) • To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients (including term neonates) ( 1.3 ) • To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).

( 1.4 ).

1.1Magnetic Resonance Imaging (MRI) of the Central Nervous System (CNS) Gadobutrol injection is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.

1.2MRI of the Breast Gadobutrol injection is indicated for use with MRI in adult patients to assess the presence and extent of malignant breast disease.

1.3Magnetic Resonance Angiography (MRA) Gadobutrol injection is indicated for use in magnetic resonance angiography (MRA) in adult and pediatric patients, including term neonates, to evaluate known or suspected supra-aortic or renal artery disease.

1.4Cardiac MRI Gadobutrol injection is indicated for use in cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION • Recommended dose for adults and pediatric patients (including term neonates) is 0.1 mL/kg body weight ( 2.1 ) • Administer as an intravenous bolus injection ( 2.2 ) • Follow injection with a normal saline flush ( 2.2 )

2.1Recommended Dose The recommended dose of gadobutrol injection for adult and pediatric patients (including term neonates) is 0.1 mL/kg body weight (0.1 mmol/kg). Refer to Table 1 to determine the volume to be administered. Table 1: Volume of Gadobutrol Injection by Body Weight *For Cardiac MRI , the dose is divided into 2 separate, equal injections Body Weight (kg) Volume to be Administered (mL) 2.5 0.25 5 0.5 10 1 15 1.5 20 2 25 2.5 30 3 35 3.5 40 4 45 4.5 50 5 60 6 70 7 80 8 90 9 100 10 110 11 120 12 130 13 140 14

2.2Administration Guidelines Gadobutrol injection is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration. Use Table 1 to determine the volume to be administered. Use sterile technique when preparing and administering gadobutrol injection.

MRI of the Central Nervous System • Administer gadobutrol injection as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second. • Follow gadobutrol injection with flush of 0.9% Sodium Chloride Injection, USP to ensure complete administration of the contrast. • Post contrast MRI can commence immediately following contrast administration. MRI of the Breast • Administer gadobutrol injection as an intravenous bolus by power injector, followed by a flush of 0.9% Sodium Chloride Injection, USP to ensure complete administration of the contrast. • Start image acquisition following contrast administration and then repeat sequentially to determine peak intensity and wash-out.

MR Angiography Image acquisition should coincide with peak arterial concentration, which varies among patients. Adults • Administer gadobutrol injection by power injector, at a flow rate of approximately 1.5 mL/second, followed by a 30 mL flush of 0.9% Sodium Chloride Injection, USP at the same rate to ensure complete administration of the contrast. Pediatric patients • Administer gadobutrol injection by power injector or manually, followed by a flush of 0.9% Sodium Chloride Injection, USP to ensure complete administration of the contrast.

Cardiac MRI • Administer gadobutrol injection through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent. • Administer gadobutrol injection as two (2) separate bolus injections: 0.05 mL/kg (0.05 mmol/kg) body weight at peak pharmacologic stress followed by 0.05 mL/kg (0.05 mmol/kg) body weight at rest. • Administer gadobutrol injection via a power injector at a flow rate of approximately 4 mL/second and follow each injection with a flush of 20 mL of 0.9% Sodium Chloride Injection, USP at the same flow rate.

2.3Drug Handling • Visually inspect gadobutrol injection for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged. • Do not mix gadobutrol injection with other medications and do not administer gadobutrol injection in the same intravenous line simultaneously with other medications because of the potential for chemical incompatibility. • Instructions of the device manufacturer must be followed.

2.4Imaging Bulk Package Preparation Instructions Gadobutrol injection Imaging Bulk Package (IBP) is a container of a sterile preparation for parenteral use that contains many single doses of gadobutrol for use with a medical imaging device. Gadobutrol injection Imaging Bulk Package is for intravenous use and not for direct infusion. Gadobutrol injection Imaging Bulk Package is for use only with an automated contrast injection system, contrast management system, or contrast media transfer set ap… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 44 words ▾

3 DOSAGE FORMS AND STRENGTHS Gadobutrol injection is a sterile, clear, and colorless to pale yellow solution for injection containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol/mL). Gadobutrol injection contains 604.72 mg gadobutrol/mL (equivalent to 1 mmol gadobutrol/mL) ( 3 )

⛔ Contraindications 26 words ▾

4 CONTRAINDICATIONS Gadobutrol injection is contraindicated in patients with history of severe hypersensitivity reactions to gadobutrol. History of severe hypersensitivity reaction to gadobutrol ( 4 )

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • Hypersensitivity Reactions: Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have occurred. Monitor patients closely during and after administration of gadobutrol. ( 5.3 ) • Acute Respiratory Distress Syndrome: For patients demonstrating respiratory distress after administration, assess oxygen requirement and monitor for worsening respiratory function.

( 5.4 ) • Gadolinium Retention: Gadolinium is retained for months or years in brain, bone, and other organs. ( 5.5 )

5.1Risk Associated with Intrathecal Use Intrathecal administration of GBCAs can cause serious adverse reactions including death, coma, encephalopathy, and seizures. The safety and effectiveness of Gadobutrol injection have not been established with intrathecal use. Gadobutrol injection is not approved for intrathecal use [see Dosage and Administration ( 2.2 )] .

5.2Nephrogenic Systemic Fibrosis GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of gadobutrol injection among these patients unless the diagnostic information is essential and not available with non-contrast MRI or other modalities. The GBCA-associated NSF risk appears highest for patients with chronic, severe kidney disease (GFR < 30 mL/min/1.73m 2 ) as well as patients with acute kidney injury.

The risk appears lower for patients with chronic, moderate kidney disease (GFR 30 to 59 mL/min/1.73m 2 ) and little, if any, for patients with chronic, mild kidney disease (GFR 60 to 89 mL/min/1.73m 2 ). NSF may result in fatal or debilitating fibrosis affecting the skin, muscle and internal organs. Report any diagnosis of NSF following gadobutrol administration to Fresenius Kabi USA, LLC at 1-800-551-7176 or FDA (1-800-FDA-1088 or www.fda.gov/medwatch).

Screen patients for acute kidney injury and other conditions that may reduce renal function. Features of acute kidney injury consist of rapid (over hours to days) and usually reversible decrease in kidney function, commonly in the setting of surgery, severe infection, injury or drug-induced kidney toxicity. Serum creatinine levels and estimated GFR may not reliably assess renal function in the setting of acute kidney injury.

For patients at risk for chronically reduced renal function (for example, age > 60 years, diabetes mellitus or chronic hypertension), estimate the GFR through laboratory testing. Among the factors that may increase the risk for NSF are repeated or higher than recommended doses of a GBCA and degree of renal impairment at the time of exposure. Record the specific GBCA and the dose administered to a patient.

For patients at highest risk for NSF, do not exceed the recommended gadobutrol dose and allow a sufficient period of time for elimination of the drug prior to re-administration. For patients receiving hemodialysis, consider the prompt initiation of hemodialysis following the administration of a GBCA in order to enhance the contrast agent's elimination [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] . The usefulness of hemodialysis in the prevention of NSF is unknown [see Clinical Pharmacology ( 12.3 )].

5.3Hypersensitivity Reactions Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following gadobutrol administration [see Adverse Reactions ( 6 )] . • Before gadobutrol administration, assess all patients for any history of a reaction to contrast media, bronchial asthma and/or allergic disorders. These patients may have an increased risk for a hypersensitivity reaction to gadobutrol. • Administer gadobutrol only in situations where trained personnel and therapies are promptly available for the treatment of hypersensitivity reactions, including personnel trained in re… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed elsewhere in labeling: • Nephrogenic Systemic Fibrosis (NSF) [see Boxed Warning and Warnings and Precautions ( 5.2 )] . • Hypersensitivity reactions [see Contraindications ( 4 ) and Warnings and Precautions ( 5.3 )] . • Acute Respiratory Distress Syndrome [see Warnings and Precautions ( 5.4 )]. • Gadolinium Retention [see Warnings and Precautions ( 5.5 )]. Most common adverse reactions (incidence ≥ 0.5%) are headache, nausea, and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC at 1-800-551-7176 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 clinical practice. The adverse reactions described in this section reflect gadobutrol exposure in 7713 subjects (including 184 pediatric patients, ages 0 to 17 years) with the majority receiving the recommended dose. Approximately 52% of the subjects were male and the ethnic distribution was 62% Caucasian, 28% Asian, 5% Hispanic, 2.5% Black, and 2.5% patients of other ethnic groups.

The average age was 56 years (range from 1 week to 93 years). Overall, approximately 4% of subjects reported one or more adverse reactions during a follow-up period that ranged from 24 hours to 7 days after gadobutrol administration. Adverse reactions associated with the use of gadobutrol were usually mild to moderate in severity and transient in nature.

Table 2 lists adverse reactions that occurred in ≥ 0.1% subjects who received gadobutrol. Table 2: Adverse Reactions Reaction Rate (%) n=7713 Headache

1.7 Nausea

1.2 Dizziness

0.5 Dysgeusia

0.4 Feeling Hot

0.4 Injection site reactions

0.4 Vomiting

0.4 Rash (includes generalized, macular, papular, pruritic)

0.3 Erythema

0.2 Paresthesia

0.2 Pruritus (includes generalized)

0.2 Dyspnea

0.1 Urticaria

0.1Adverse reactions that occurred with a frequency of < 0.1% in subjects who received gadobutrol include: hypersensitivity/anaphylactic reaction, loss of consciousness, convulsion, parosmia, tachycardia, palpitation, dry mouth, malaise and feeling cold.

6.2Postmarketing Experience The following additional adverse reactions have been identified during postmarketing use of gadobutrol or other GBCAs. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. • Cardiac arrest • Nephrogenic Systemic Fibrosis (NSF) • Hypersensitivity reactions (anaphylactic shock, circulatory collapse, respiratory arrest, bronchospasm, cyanosis, oropharyngeal swelling, laryngeal edema, blood pressure increased, chest pain, angioedema, conjunctivitis, hyperhidrosis, cough, sneezing, burning sensation, and pallor). • Respiratory, Thoracic, and Mediastinal Disorders: Acute respiratory distress syndrome, pulmonary edema • General Disorders and Administration Site Conditions: Adverse reactions with variable onset and duration have been reported after GBCA administration.

These include fatigue, asthenia, pain syndromes, and heterogeneous clusters of symptoms in the neurological, cutaneous, and musculoskeletal systems. • Skin: Gadolinium associated plaques • Gastrointestinal Disorders: Acute pancreatitis with onset within 48 hours after GBCA administration

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Use only if imaging is essential during pregnancy and cannot be delayed. ( 8.1 )

8.1Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive (see Data ) . In animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose.

Retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see Data ) . Because of the potential risks of gadolinium to the fetus, use gadobutrol only if imaging is essential during pregnancy and cannot be delayed. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and is 15% to 20%, respectively. Data Human Data Contrast enhancement is visualized in the placenta and fetal tissues after maternal GBCA administration. Cohort studies and case reports on exposure to GBCAs during pregnancy have not reported a clear association between GBCAs and adverse effects in the exposed neonates.

However, a retrospective cohort study, comparing pregnant women who had a GBCA MRI to pregnant women who did not have an MRI, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving GBCA MRI. Limitations of this study include a lack of comparison with non-contrast MRI and lack of information about the maternal indication for MRI. Overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of GBCAs in pregnancy.

Animal Data Gadolinium Retention GBCAs administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. GBCAs administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. Reproductive Toxicology Embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose.

Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses).

Because pregnant animals received repeated daily doses of gadobutrol, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans.

8.2Lactation Risk Summary There are no data on the presence of gadobutrol in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01% to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited GBCA gastrointestinal absorption in the breast-fed infant. Gadobutrol is present in rat milk (see Data ) .

The developmental and health benefits of breastfeeding should… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary GBCAs cross the placenta and result in fetal exposure and gadolinium retention. The human data on the association between GBCAs and adverse fetal outcomes are limited and inconclusive (see Data ) . In animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose.

Retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see Data ) . Because of the potential risks of gadolinium to the fetus, use gadobutrol only if imaging is essential during pregnancy and cannot be delayed. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and is 15% to 20%, respectively. Data Human Data Contrast enhancement is visualized in the placenta and fetal tissues after maternal GBCA administration. Cohort studies and case reports on exposure to GBCAs during pregnancy have not reported a clear association between GBCAs and adverse effects in the exposed neonates.

However, a retrospective cohort study, comparing pregnant women who had a GBCA MRI to pregnant women who did not have an MRI, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving GBCA MRI. Limitations of this study include a lack of comparison with non-contrast MRI and lack of information about the maternal indication for MRI. Overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of GBCAs in pregnancy.

Animal Data Gadolinium Retention GBCAs administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. GBCAs administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. Reproductive Toxicology Embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose.

Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses).

Because pregnant animals received repeated daily doses of gadobutrol, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans.

🧒 Pediatric Use ~2 min read ▾

8.4Pediatric Use The safety and effectiveness of gadobutrol have been established in pediatric patients, including term neonates, for use with MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system and for use in MRA to evaluate known or suspected supra-aortic or renal artery disease. Use of gadobutrol in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with CNS and non-CNS lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] .

The frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [ s ee Adverse Reactions ( 6.1 )] . No dose adjustment according to age is necessary in pediatric patients [see Dosage and Administration ( 2.1 ), Clinical Pharmacology ( 12.3 ), and Clinical Studies ( 14.1 )] . The safety and effectiveness of gadobutrol have not been established in preterm neonates for any indication or in pediatric patients of any age for use with MRI to assess the presence and extent of malignant breast disease, or for use in CMRI to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (CAD).

NSF Risk No case of NSF associated with gadobutrol or any other GBCA has been identified in pediatric patients ages 6 years and younger. Pharmacokinetic studies suggest that clearance of gadobutrol is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. No increased risk factor for NSF has been identified in juvenile animal studies of gadobutrol.

Normal estimated GFR (eGFR) is around 30 mL/min/1.73m 2 at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. Clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum eGFR: 31 mL/min/1.73m 2 (age 2 to 7 days), 38 mL/min/1.73m 2 (age 8 to 28 days), 62 mL/min/1.73m 2 (age 1 to 6 months), and 83 mL/min/1.73m 2 (age 6 to 12 months). Juvenile Animal Data Single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants.

🧓 Geriatric Use 96 words ▾

8.5Geriatric Use In clinical studies of gadobutrol, 1,377 patients were 65 years of age and over, while 104 patients were 80 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, use of gadobutrol in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy.

No dose adjustment according to age is necessary in this population.

🆘 Overdosage 52 words ▾

10 OVERDOSAGE The maximum dose of gadobutrol tested in healthy volunteers, 1.5 mL/kg body weight (1.5 mmol/kg; 15 times the recommended dose), was tolerated in a manner similar to lower doses. Gadobutrol can be removed by hemodialysis [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] .

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occurs with: • Differences in proton density • Differences of the spin-lattice or longitudinal relaxation times (T 1 ) • Differences in the spin-spin or transverse relaxation time (T 2 ) When placed in a magnetic field, gadobutrol shortens the T 1 and T 2 relaxation times. The extent of decrease of T 1 and T 2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol, is based upon several factors including the concentration of gadobutrol in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times.

At the recommended dose, the T 1 shortening effect is observed with greatest sensitivity in T 1 -weighted magnetic resonance sequences. In T 2 *-weighted sequences the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.

12.2Pharmacodynamics Gadobutrol leads to distinct shortening of the relaxation times even in low concentrations. At pH 7, 37°C and

1.5T, the relaxivity (r 1 ) - determined from the influence on the relaxation times (T 1 ) of protons in plasma - is

5.2L/(mmol·sec) and the relaxivity (r 2 ) - determined from the influence on the relaxation times (T 2 ) - is

6.1L/(mmol·sec). These relaxivities display only slight dependence on the strength of the magnetic field. The T 1 shortening effect of paramagnetic contrast agents is dependent on concentration and r 1 relaxivity (see Table 3 ). This may improve tissue visualization. Table 3: Relaxivity (r 1 ) of Gadolinium Chelates at

1.5T r 1 relaxivity in plasma at 37°C Gadolinium-Chelate r 1 (L·mmol -1 ·s -1 ) Gadobenate

6.3 Gadobutrol

5.2 Gadodiamide

4.3 Gadofosveset 16 Gadopentetate

4.1 Gadoterate

3.6 Gadoteridol

4.1 Gadoversetamide

4.7 Gadoxetate

6.9Compared to 0.5 molar gadolinium-based contrast agents, the higher concentration of gadobutrol results in half the volume of administration and a more compact contrast bolus injection. At the site of imaging, the relative height and width of the time intensity curve for gadobutrol varies as a function of imaging location and multiple patient, injection, and device-specific factors. Gadobutrol is a water-soluble, hydrophilic compound with a partition coefficient between n-butanol and buffer at pH 7.6 of about 0.006.

12.3Pharmacokinetics Distribution After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding.

Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs [see Warnings and Precautions ( 5.5 )] . Metabolism Gadobutrol is not metabolized. Elimination Values for AUC, body weight normalized plasma clearance and half-life are given in Table 4 , below.

Gadobutrol is excreted in an unchanged form via the kidneys. In healthy subjects, renal clearance of gadobutrol is 1.1 to 1.7 mL/(min∙kg) and thus comparable to the renal clearance of inulin, confirming that gadobutrol is eliminated by glomerular filtration. Within two hours after intravenous administration more than 50% and within 12 hours more than 90% of the given dose is eliminated via the urine.

Extra-renal elimination is negligible. Specific Populations Gender Gender has no clinically relevant effect on the pharmacokinetics of gadobutrol. Geriatric A single intravenous dose of 0.1 mmol/kg gadobutrol was administered to 15 elderly and 16 non-elderly subjects.

AUC was slightly higher and clearance slightly lower in elderly sub… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 175 words ▾

12.1Mechanism of Action In MRI, visualization of normal and pathological tissue depends in part on variations in the radiofrequency signal intensity that occurs with: • Differences in proton density • Differences of the spin-lattice or longitudinal relaxation times (T 1 ) • Differences in the spin-spin or transverse relaxation time (T 2 ) When placed in a magnetic field, gadobutrol shortens the T 1 and T 2 relaxation times. The extent of decrease of T 1 and T 2 relaxation times, and therefore the amount of signal enhancement obtained from gadobutrol, is based upon several factors including the concentration of gadobutrol in the tissue, the field strength of the MRI system, and the relative ratio of the longitudinal and transverse relaxation times.

At the recommended dose, the T 1 shortening effect is observed with greatest sensitivity in T 1 -weighted magnetic resonance sequences. In T 2 *-weighted sequences the induction of local magnetic field inhomogeneities by the large magnetic moment of gadolinium and at high concentrations (during bolus injection) leads to a signal decrease.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Gadobutrol injection is a sterile, clear and colorless to pale yellow solution containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol per mL). Gadobutrol injection is supplied in the following Multiple-Dose container sizes: Product Code Unit of Sale Each 287230 NDC 65219-287-30 Packaged in cartons of 10. NDC 65219-287-10 30 mL Imaging Bulk Package with rubber stopper.

287265 NDC 65219-289-65 Packaged in cartons of 10. NDC 65219-289-10 65 mL Imaging Bulk Package with rubber stopper.

16.2Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Should freezing occur, gadobutrol injection should be brought to room temperature before use. If allowed to stand at room temperature, gadobutrol injection should return to a clear and colorless to pale yellow solution.

Visually inspect gadobutrol injection for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.

16.1How Supplied Gadobutrol injection is a sterile, clear and colorless to pale yellow solution containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol per mL). Gadobutrol injection is supplied in the following Multiple-Dose container sizes: Product Code Unit of Sale Each 287230 NDC 65219-287-30 Packaged in cartons of 10. NDC 65219-287-10 30 mL Imaging Bulk Package with rubber stopper.

287265 NDC 65219-289-65 Packaged in cartons of 10. NDC 65219-289-10 65 mL Imaging Bulk Package with rubber stopper.

📦 Storage and Handling 87 words ▾

16.2Storage and Handling Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Should freezing occur, gadobutrol injection should be brought to room temperature before use. If allowed to stand at room temperature, gadobutrol injection should return to a clear and colorless to pale yellow solution.

Visually inspect gadobutrol injection for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored, if particulate matter is present or if the container appears damaged.

📋 Description 158 words ▾

11 DESCRIPTION Gadobutrol injection is a paramagnetic macrocyclic contrast agent administered intravenously for magnetic resonance imaging. The chemical name for gadobutrol is 10–[(1SR,2RS)–2,3–dihydroxy–1–hydroxymethylpropyl]–1,4,7,10– tetraazacyclododecane–1,4,7–triacetic acid, gadolinium complex. Gadobutrol has a molecular formula of C 18 H 31 GdN 4 O 9 and a molecular weight of 604.72.

Gadobutrol injection is a sterile, clear, colorless to pale yellow solution containing 604.72 mg (1.0 mmol) of gadobutrol per mL as the active ingredient with 0.513 mg of calcobutrol sodium, 1.211 mg of trometamol, hydrochloric acid (for pH adjustment) and water for injection. Gadobutrol injection contains no preservatives. The main physicochemical properties of gadobutrol injection (1 mmol/mL solution for injection) are listed below: Density (g/mL at 37°C)

1.3Osmolarity at 37°C (mOsm/L solution) 1117 Osmolality at 37°C (mOsm/kg H 2 O) 1603 Viscosity at 37°C (mPa·s) 4.96 pH 6.6 to 8 The thermodynamic stability constants for gadobutrol (log Ktherm and log Kcond at pH 7.4) are 21.8 and 15.3, respectively. gadob-struc-01.jpg

💬 Information for Patients ~2 min read ▾

17 PATIENT COUNSELING INFORMATION • Advise the patient to read the FDA-approved patient labeling ( Medication Guide ). Nephrogenic Systemic Fibrosis Instruct patients to inform their physician if they: • Have a history of kidney disease and/or liver disease, or • Have recently received a GBCA GBCAs increase the risk of NSF among patients with impaired elimination of drugs. To counsel patients at risk of NSF: • Describe the clinical manifestation of NSF • Describe procedures to screen for the detection of renal impairment Instruct the patients to contact their physician if they develop signs or symptoms of NSF following gadobutrol injection administration, such as burning, itching, swelling, scaling, hardening and tightening of the skin; red or dark patches on the skin; stiffness in joints with trouble moving, bending or straightening the arms, hands, legs or feet; pain in the hip bones or ribs; or muscle weakness.

Common Adverse Reactions Inform patients that they may experience: • Reactions along the venous injection site, such as mild and transient burning or pain or feeling of warmth or coldness at the injection site • Side effects of headache, nausea, abnormal taste and feeling hot Acute Respiratory Distress Syndrome • Advise patients that acute respiratory distress syndrome (ARDS) has occurred with gadobutrol injection. Inform patients on the symptoms of the observed ARDS cases, and instruct patients to inform their healthcare provider if they experience these symptoms [see Warnings and Precautions ( 5.4 )] .

General Precautions Gadolinium Retention • Advise patients that gadolinium is retained for months or years in brain, bone, skin, and other organs in patients with normal renal function. The clinical consequences of retention are unknown. Retention depends on multiple factors and is greater following administration of linear GBCAs than following administration of macrocyclic GBCAs [see Warnings and Precautions ( 5.5 )] .

Instruct patients receiving gadobutrol injection to inform their physician if they: • Are pregnant or breastfeeding • Have a history of allergic reaction to contrast media, bronchial asthma or allergic respiratory disorder Manufactured for: Lake Zurich, IL 60047 www.fresenius-kabi.com/us Product of China Revised: May 2025 451796C 26EUF04 gadob-img-01.jpg

💬 Medication Guide ~3 min read ▾

MEDICATION GUIDE Gadobutrol Injection Gadobutrol (“gad” oh bue' trol) Injection for intravenous use What is the most important information I should know about gadobutrol injection? • GBCAs like Gadobutrol injection may cause serious side effects including death, coma, encephalopathy, and seizures when it is given intrathecally (injection given into the spinal canal). It is not known if Gadobutrol injection is safe and effective with intrathecal use. Gadobutrol injection is not approved for this use. • Gadobutrol injection contains a metal called gadolinium.

Small amounts of gadolinium can stay in your body including the brain, bones, skin and other parts of your body for a long time (several months to years). • It is not known how gadolinium may affect you, but so far, studies have not found harmful effects in patients with normal kidneys. • Rarely, patients have reported pains, tiredness, and skin, muscle or bone ailments for a long time, but these symptoms have not been directly linked to gadolinium. • There are different GBCAs that can be used for your MRI exam. The amount of gadolinium that stays in the body is different for different gadolinium medicines.

Gadolinium stays in the body more after Omniscan or Optimark than after Eovist, Magnevist, or MultiHance. Gadolinium stays in the body the least after Dotarem, Gadobutrol injection, or ProHance. • People who get many doses of gadolinium medicines, women who are pregnant and young children may be at increased risk from gadolinium staying in the body. • Some people with kidney problems who get gadolinium medicines can develop a condition with severe thickening of the skin, muscles and other organs in the body (nephrogenic systemic fibrosis).

Your healthcare provider should screen you to see how well your kidneys are working before you receive gadobutrol injection. What is gadobutrol injection? • Gadobutrol injection is a prescription medicine called a gadolinium-based contrast agent (GBCA). Gadobutrol injection, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner. • An MRI exam with a GBCA, including gadobutrol injection, helps your doctor to see problems better than an MRI exam without a GBCA. • Your doctor has reviewed your medical records and has determined that you would benefit from using a GBCA with your MRI exam.

Do not receive gadobutrol injection if you have had a severe allergic reaction to gadobutrol injection. Before receiving gadobutrol injection, tell your healthcare provider about all your medical conditions, including if you: • have had any MRI procedures in the past where you received a GBCA. Your healthcare provider may ask you for more information including the dates of these MRI procedures. • are pregnant or plan to become pregnant.

It is not known if gadobutrol injection can harm your unborn baby. Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as gadobutrol injection is received during pregnancy. • have kidney problems, diabetes, or high blood pressure • have had an allergic reaction to dyes (contrast agents) including GBCAs What are the possible side effects of gadobutrol injection? • See “What is the most important information I should know about gadobutrol injection?” • Allergic reactions. Gadobutrol injection can cause allergic reactions that can sometimes be serious.

Your healthcare provider will monitor you closely for symptoms of an allergic reaction. • A serious lung problem called acute respiratory distress syndrome (ARDS). Call your healthcare provider right away if you have shortness of breath with or without a fever, trouble breathing, or a fast rate of breathing after receiving gadobutrol injection. The most common side effects of gadobutrol injection include: headache, nausea, and dizziness.

These are not all the possible side effects of gadobutrol injection. Call your doctor for medical advice about side effects. You may report side effects to F… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Distribution After intravenous administration, gadobutrol is rapidly distributed in the extracellular space. After a gadobutrol dose of 0.1 mmol/kg body weight, an average level of 0.59 mmol gadobutrol/L was measured in plasma 2 minutes after the injection and 0.3 mmol gadobutrol/L 60 minutes after the injection. Gadobutrol does not display any particular protein binding.

Following GBCA administration, gadolinium is present for months or years in brain, bone, skin, and other organs [see Warnings and Precautions ( 5.5 )] . Metabolism Gadobutrol is not metabolized. Elimination Values for AUC, body weight normalized plasma clearance and half-life are given in Table 4 , below.

Gadobutrol is excreted in an unchanged form via the kidneys. In healthy subjects, renal clearance of gadobutrol is 1.1 to 1.7 mL/(min∙kg) and thus comparable to the renal clearance of inulin, confirming that gadobutrol is eliminated by glomerular filtration. Within two hours after intravenous administration more than 50% and within 12 hours more than 90% of the given dose is eliminated via the urine.

Extra-renal elimination is negligible. Specific Populations Gender Gender has no clinically relevant effect on the pharmacokinetics of gadobutrol. Geriatric A single intravenous dose of 0.1 mmol/kg gadobutrol was administered to 15 elderly and 16 non-elderly subjects.

AUC was slightly higher and clearance slightly lower in elderly subjects as compared to non-elderly subjects [see Use in Specific Populations ( 8.5 )]. Pediatric The pharmacokinetics of gadobutrol were evaluated in two studies in a total of 130 patients age 2 to less than 18 years and in 43 patients less than 2 years of age (including term neonates). Patients received a single intravenous dose of 0.1 mmol/kg of gadobutrol.

The pharmacokinetic profile of gadobutrol in pediatric patients is similar to that in adults, resulting in similar values for AUC, body weight normalized plasma clearance, as well as elimination half-life. Approximately 99% (median value) of the dose was recovered in urine within 6 hours (this information was derived from the 2 to less than 18 year old age group). Table 4: Pharmacokinetics by Age Group (Median [Range]) 0 to < 2 years N=43 2 to 6 years N=45 7 to 11 years N=39 12 to < 18 years N=46 Adults N=93 AUC (μmolxh/L) 781 [513, 1891] 846 [412, 1331] 1025 [623, 2285] 1237 [946, 2211] 1072 [667, 1992] CL (L/h/kg) 0.128 [0.053, 0.195] 0.119 [0.08, 0.215] 0.099 [0.043, 0.165] 0.081 [0.046, 0.103] 0.094 [0.051, 0.150] t1/2 (h) 2.91 [1.60, 12.4] 1.91 [1.04, 2.70] 1.66 [0.91, 2.71] 1.68 [1.31, 2.48] 1.80 [1.20, 6.55] C20 (μmol/L) 367 [280, 427] 421 [369, 673] 462 [392, 760] 511 [387, 1077] 441 [281, 829] Renal Impairment In patients with impaired renal function, the serum half-life of gadobutrol is prolonged and correlated with the reduction in creatinine clearance.

After intravenous injection of 0.1 mmol gadobutrol/kg body weight, the elimination half-life was 5.8 ± 2.4 hours in mild to moderately impaired patients (80 > CLCR > 30 mL/min) and 17.6 ± 6.2 hours in severely impaired patients not on dialysis (CLCR< 30 mL/min). The mean AUC of gadobutrol in patients with normal renal function was 1.1 ± 0.1 mmol∙h/L, compared to 4.0 ± 1.8 mmol∙h/L in patients with mild to moderate renal impairment and 11.5 ± 4.3 mmol∙h/L in patients with severe renal impairment. Complete recovery in the urine was seen in patients with mild or moderate renal impairment within 72 hours.

In patients with severely impaired renal function about 80% of the administered dose was recovered in the urine within 5 days. For patients receiving hemodialysis, physicians may consider the prompt initiation of hemodialysis following the administration of gadobutrol in order to enhance the contrast agent's elimination. Sixty-eight percent (68%) of gadobutrol is removed from the body after the first dialysis, 94% after the second dialysis, and 98% after the third dialysis session. [see Warnings and P… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~1 min read ▾

12.2Pharmacodynamics Gadobutrol leads to distinct shortening of the relaxation times even in low concentrations. At pH 7, 37°C and

1.5T, the relaxivity (r 1 ) - determined from the influence on the relaxation times (T 1 ) of protons in plasma - is

5.2L/(mmol·sec) and the relaxivity (r 2 ) - determined from the influence on the relaxation times (T 2 ) - is

6.1L/(mmol·sec). These relaxivities display only slight dependence on the strength of the magnetic field. The T 1 shortening effect of paramagnetic contrast agents is dependent on concentration and r 1 relaxivity (see Table 3 ). This may improve tissue visualization. Table 3: Relaxivity (r 1 ) of Gadolinium Chelates at

1.5T r 1 relaxivity in plasma at 37°C Gadolinium-Chelate r 1 (L·mmol -1 ·s -1 ) Gadobenate

6.3 Gadobutrol

5.2 Gadodiamide

4.3 Gadofosveset 16 Gadopentetate

4.1 Gadoterate

3.6 Gadoteridol

4.1 Gadoversetamide

4.7 Gadoxetate

6.9Compared to 0.5 molar gadolinium-based contrast agents, the higher concentration of gadobutrol results in half the volume of administration and a more compact contrast bolus injection. At the site of imaging, the relative height and width of the time intensity curve for gadobutrol varies as a function of imaging location and multiple patient, injection, and device-specific factors. Gadobutrol is a water-soluble, hydrophilic compound with a partition coefficient between n-butanol and buffer at pH 7.6 of about 0.006.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES

14.1MRI of the CNS Patients referred for MRI of the central nervous system with contrast were enrolled in two clinical trials that evaluated the visualization characteristics of lesions. In both studies, patients underwent a baseline, pre-contrast MRI prior to administration of gadobutrol at a dose of 0.1 mmol/kg, followed by a post-contrast MRI. In Study A, patients also underwent an MRI before and after the administration of gadoteridol.

The studies were designed to demonstrate superiority of gadobutrol MRI to non-contrast MRI for lesion visualization. For both studies, pre-contrast and pre-plus-post contrast images (paired images) were independently evaluated by three readers for contrast enhancement and border delineation using a scale of 1 to 4, and for internal morphology using a scale of 1 to 3 ( Table 5 ). Lesion counting was also performed to demonstrate non-inferiority of paired gadobutrol image sets to pre-contrast MRI.

Readers were blinded to clinical information. Table 5: Primary Endpoint Visualization Scoring System Score Visualization Characteristics Contrast Enhancement Border Delineation Internal Morphology 1 None None Poorly visible 2 Weak Moderate Moderately visible 3 Clear Clear but incomplete Sufficiently visible 4 Clear and bright Clear and complete N/A Efficacy was determined in 657 subjects. The average age was 49 years (range 18 to 85 years) and 42% were male.

The ethnic representations were 39% Caucasian, 4% Black, 16% Hispanic, 38% Asian, and 3% of other ethnic groups. Table 6 shows a comparison of visualization results between paired images and pre-contrast images. Gadobutrol provided a statistically significant improvement for each of the three lesion visualization parameters when averaged across three independent readers for each study.

Table 6: Visualization Endpoint Results of Central Nervous System Adult MRI Studies with 0.1 mmol/kg Gadobutrol 1 Difference of means = (paired mean) – (pre-contrast mean) 2 p<0.001 3 Met noninferiority margin of -0.35 4 Did not meet noninferiority margin of -0.35 Endpoint Study A N=336 Study B N=321 Pre-contrast Paired Difference 1 Pre-contrast Paired Difference Contrast Enhancement 0.97 2.26 1.29 2 0.93 2.86 1.94 2 Border Delineation 1.98 2.58 0.60 2 1.92 2.94 1.02 2 Internal Morphology 1.32 1.93 0.60 2 1.57 2.35 0.78 2 Average # Lesions Detected 8.08 8.25 0.17 4 2.65 2.97 0.32 3 Performances of gadobutrol and gadoteridol for visualization parameters were similar.

Regarding the number of lesions detected, Study B met the prespecified noninferiority margin of -0.35 for paired read versus pre-contrast read while in Study A, gadobutrol and gadoteridol did not. For the visualization endpoints contrast enhancement, border delineation, and internal morphology, the percentage of patients scoring higher for paired images compared to pre-contrast images ranged from 93% to 99% for Study A, and 95% to 97% for Study B. For both studies, the mean number of lesions detected on paired images exceeded that of the pre-contrast images; 37% for Study A and 24% for Study B.

There were 29% and 11% of subjects in which the pre-contrast images detected more lesions for Study A and Study B, respectively. The percentage of patients whose average reader mean score changed by ≤ 0, up to 1, up to 2, and ≥ 2 scoring categories presented in Table 5 is shown in Table 7 . The categorical improvement of (≤ 0) represents higher (< 0) or identical (= 0) scores for the pre-contrast read, the categories with scores > 0 represent the magnitude of improvement seen for the paired read.

Table 7: Primary Endpoint Visualization Categorical Improvement for Average Reader Study A N=336 Study B N=321 Endpoint Categorical Improvement (Paired – Pre-Contrast) % Categorical Improvement (Paired – Pre-Contrast) % ≤ 0 > 0 to < 1 1 to < 2 ≥ 2 ≤ 0 > 0 to < 1 1 to < 2 ≥ 2 Contrast Enhancement 1 30 55 13 3 6 34 57 Border Delineation 7 73 18 1 5 38 51 5 Internal Morphology 4 79 17 0 5 61 33 1 For bo… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology 149 words ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity studies of gadobutrol have been conducted. Gadobutrol was not mutagenic in in vitro reverse mutation tests in bacteria, in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using cultured Chinese hamster V79 cells, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an in vivo micronucleus test in mice after intravenous injection of 0.5 mmol/kg. Gadobutrol had no effect on fertility and general reproductive performance of male and female rats when given in doses 12.2 times the human equivalent dose (based on body surface area).

13.2Animal Toxicology and/or Pharmacology Local intolerance reactions, including moderate irritation associated with infiltration of inflammatory cells was observed after paravenous administration to rabbits, suggesting the possibility of occurrence of local irritation if the contrast medium leaks around veins in a clinical setting [see Warnings and Precautions ( 5.7 )].

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 96 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity studies of gadobutrol have been conducted. Gadobutrol was not mutagenic in in vitro reverse mutation tests in bacteria, in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using cultured Chinese hamster V79 cells, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an in vivo micronucleus test in mice after intravenous injection of 0.5 mmol/kg. Gadobutrol had no effect on fertility and general reproductive performance of male and female rats when given in doses 12.2 times the human equivalent dose (based on body surface area).

📄 Recent Major Changes 11 words ▾

Warnings and Precautions, Acute Respiratory Distress Syndrome ( 5.4 ) 3/2025

📄 Package Label / Principal Display Panel ~1 min read ▾

PRINCIPAL DISPLAY PANEL – 30 mmol/30 mL (1 mmol/mL) – Shelf Carton Dose: 0.1 mL/kg NDC 65219- 287 -30 Gadobutrol Injection 30 mmol/30 mL (1 mmol/mL) Imaging Bulk Package - Not for Direct Infusion For Intravenous Use Only Discard 24 hours after initial puncture Dispense the enclosed Medication Guide to each patient. gadob-label-01.jpg

PRINCIPAL DISPLAY PANEL – 30 mmol/30 mL (1 mmol/mL) – Bottle Label Dose: 0.1 mL/kg NDC 65219- 287 -10 Gadobutrol Injection 30 mmol/30 mL (1 mmol/mL) Imaging Bulk Package - Not for Direct Infusion For Intravenous Use Only Multiple-Dose Bottle Discard 24 hours after initial puncture Discard after ___ / ___ / ___ at ___ : ___ gadob-label-02.jpg

PRINCIPAL DISPLAY PANEL – 65 mmol/65 mL (1 mmol/mL) – Shelf Carton Dose: 0.1 mL/kg NDC 65219- 289 -65 Gadobutrol Injection 65 mmol/65 mL (1 mmol/mL) Imaging Bulk Package - Not for Direct Infusion For Intravenous Use Only Discard 24 hours after initial puncture Dispense the enclosed Medication Guide to each patient. gadob-label-03.jpg

PRINCIPAL DISPLAY PANEL – 65 mmol/65 mL (1 mmol/mL) – Bottle Label Dose: 0.1 mL/kg NDC 65219- 289 -10 Gadobutrol Injection 65 mmol/65 mL (1 mmol/mL) Imaging Bulk Package - Not for Direct Infusion For Intravenous Use Only Multiple-Dose Bottle Discard 24 hours after initial puncture Discard after ___ / ___ / ___ at ___ : ___ gadob-label-04.jpg

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 – Q4 2025 · 3 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
13
Units reimbursed last 4 qtrs
109
Gross reimbursed last 4 qtrs
$291.80
Avg / prescription
$22.45
Avg / unit
$2.6845
Latest quarter Q4 2025
0Rx
Fee-for-service vs managed care ⓘ
100% MCO
Fee-for-service · 0 Rx Managed care · 13 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: 109 units · 0.8 per 100k residents PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: no data reported 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
0.80.8
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 Pennsylvania 0.8 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

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 ✓ Available
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 — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope.
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 Fresenius Kabi USA, LLC. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Fresenius Kabi USA, LLC 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 A9585 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.
← 65219-0287-30 · Fresenius 65219-0292-77 · FRESENIUS →
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.