PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL

Gadavist Imaging Bulk Pack 65 mL Label

Dose: 0.1 mL/kg

NDC 50419-325-09
65 mL

Rx only

sterile solution

Gadavist

sterile solution

Gadavist

(gadobutrol) injection
1 mmol/mL

For Intravenous Administration.
Multiple-Dose container.

Discard unused portion 24 hours after initial puncture.

RECENT MAJOR CHANGES SECTION

RECENT MAJOR CHANGES

Boxed Warning 1/2024

Warnings and Precautions,Risk Associated with Intrathecal Use (5.1) 1/2024

DOSAGE & ADMINISTRATION SECTION

Highlight: •

Recommended dose for adults and pediatric patients (including term neonates) is 0.1 mL/kg body weight (2.1) 

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Administer as an intravenous bolus injection (2.2)

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Follow injection with intravenous flush of 0.9% Sodium Chloride Injection, USP (2.2)

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See Full Prescribing Information for dosing, preparation, administration, and handling (2)

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dose

The recommended dose of Gadavist 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.

2.2 Administration Guidelines

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Gadavist 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.

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Use sterile technique when preparing and administering Gadavist.

MRI of the Central Nervous System

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Administer Gadavist as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second. 

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Follow Gadavist injection with flush of 0.9% Sodium Chloride Injection, USP to ensure complete administration of the contrast. 

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Post contrast MRI can commence immediately following contrast administration.

MRI of the Breast

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Administer Gadavist 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. 

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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

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Administer Gadavist 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

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Administer Gadavist 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

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 Administer Gadavist through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent. 

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 Administer Gadavist 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. 

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 Administer Gadavist 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.

2.3 Drug Handling

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Visually inspect Gadavist 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. 

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Do not mix Gadavist with other medications and do not administer Gadavist in the same intravenous line simultaneously with other medications because of the potential for chemical incompatibility.

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Instructions of the device manufacturer must be followed.

2.4 Imaging Bulk Package Preparation Instruction

Gadavist 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. Gadavist Imaging Bulk Package is for intravenous use and not for direct infusion. Gadavist Imaging Bulk Package is for use only with an automated contrast injection system, contrast management system, or contrast media transfer set approved or cleared for use with this contrast agent in this Imaging Bulk Package. Please see drug and device labeling for information on devices indicated for use with this Imaging Bulk Package and techniques to help assure safe use.

The Gadavist Imaging Bulk Package is to be used only in a room designated for radiological procedures that involve intravascular administration of a contrast agent. 

Utilize aseptic technique for penetrating the container closure of the Gadavist Imaging Bulk Package and transferring Gadavist injection. 

The container closure must be penetrated only one time with a suitable sterile component of the automated contrast injection system, contrast management system, or contrast media transfer set (e.g. transfer spike) approved or cleared for use with this contrast agent in this Imaging Bulk Package.

Once the Gadavist Imaging Bulk Package is punctured, do not remove it from the work area during the entire period of use. Storage temperature of Gadavist Imaging Bulk Package after the closure has been entered is 20°C to 25°C (68°F to 77°F).

A maximum use time of 24 hours from initial puncture is permitted to complete fluid transfer. Discard any unused Gadavist injection 24 hours after initial puncture of the Imaging Bulk Package.

After the container closure is punctured, if the integrity of the Imaging Bulk Package and the delivery system cannot be assured through direct continuous supervision, the Imaging Bulk Package and all associated disposables for the automated contrast injection system, contrast management system, or contrast media transfer set (e.g. transfer spike) should be discarded.

DOSAGE FORMS & STRENGTHS SECTION

Highlight: Gadavist injection contains 604.72 mg gadobutrol/mL (equivalent to 1 mmol gadobutrol/mL (3)

3 DOSAGE FORMS AND STRENGTHS

Gadavist 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).

CONTRAINDICATIONS SECTION

Highlight: History of severe hypersensitivity reaction to Gadavist (4)

4 CONTRAINDICATIONS

Gadavist is contraindicated in patients with history of severe hypersensitivity reactions to Gadavist.

Boxed Warning section

WARNING: RISK ASSOCIATED WITH INTRATHECAL USE and NEPHROGENIC SYSTEMIC

FIBROSIS

See full prescribing information for complete boxed warning

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**Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadavist is not approved for intrathecal use (****5.1****)**

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**GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of Gadavist 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:**

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**Chronic, severe kidney disease (GFR < 30 mL/min/1.73m****2****), or**

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**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****)**

INFORMATION FOR PATIENTS SECTION

17 PATIENT COUNSELING INFORMATION

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Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Nephrogenic Systemic Fibrosis

Instruct patients to inform their physician if they:

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Have a history of kidney disease and/or liver disease, or

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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:

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Describe the clinical manifestation of NSF

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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 Gadavist 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:

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Reactions along the venous injection site, such as mild and transient burning or pain or feeling of warmth or coldness at the injection site 

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Side effects of headache, nausea, abnormal taste and feeling hot

General Precautions

Gadolinium Retention

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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 (5.4)].

Instruct patients receiving Gadavist to inform their physician if they:

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Are pregnant or breastfeeding

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Have a history of allergic reaction to contrast media, bronchial asthma or allergic respiratory disorder. 

© 2020, Bayer HealthCare Pharmaceuticals Inc. All rights reserved.

Manufactured for:

Bayer HealthCare Pharmaceuticals Inc.
Whippany, NJ 07981

Manufactured in Germany

SPL MEDGUIDE SECTION

Medication Guide

**GADAVIST (gad-a-vist) (gadobutrol)**
**Injection for intravenous use**

**What is Gadavist?**

Gadavist is a prescription medicine called a gadolinium-based contrast agent (GBCA). Gadavist, like other GBCAs, is injected into your vein and used with a magnetic resonance imaging (MRI) scanner.

An MRI exam with a GBCA, including Gadavist, 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.

**What is the most important information I should know about Gadavist?**

GBCAs like Gadavist 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 Gadavist is safe and effective with intrathecal use. Gadavist is not approved for this use.

Gadavist 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, Gadavist, 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 Gadavist.

**Do not receive Gadavist if you**have had a severe allergic reaction to Gadavist.

**Before receiving Gadavist, 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 Gadavist can harm your unborn baby. Talk to your healthcare provider about the possible risks to an unborn baby if a GBCA such as Gadavist 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 Gadavist?**

**See “What is the most important information I should know about Gadavist?”**

**Allergic reactions. Gadavist can cause allergic reactions that can sometimes be serious. Your healthcare provider will monitor you closely for symptoms of an allergic reaction.**
**The most common side effects of Gadavist include: headache, nausea, and dizziness.**
These are not all the possible side effects of Gadavist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

**General information about the safe and effective use of Gadavist.**
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. You can ask your healthcare provider for information about Gadavist that is written for health professionals.

**What are the ingredients in Gadavist?**
Active ingredient: gadobutrol
Inactive ingredients: calcobutrol sodium, trometamol, hydrochloric acid (for pH adjustment) and water for injection Manufactured for Bayer HealthCare Pharmaceuticals Inc.
Manufactured in Germany © 2011
Bayer HealthCare Pharmaceuticals Inc. All rights reserved.
For more information, go to [www.gadavist.com ](http://www.gadavist.com/)or call 1-888-842-2937.

HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Gadavist is a sterile, clear and colorless to pale yellow solution containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol) per mL. Gadavist is supplied in the following Multiple-Dose container sizes:

30 mL Imaging Bulk Package, rubber stoppered in cartons of 5, Boxes of 10 (NDC 50419-325-18)

65 mL Imaging Bulk Package, rubber stoppered, Boxes of 10 (NDC 50419-325-19)

16.2 Storage and Handling

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [see USP Controlled Room Temperature].

Should freezing occur, Gadavist should be brought to room temperature before use. If allowed to stand at room temperature, Gadavist should return to a clear and colorless to pale yellow solution. Visually inspect Gadavist 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.