GADAVIST- gadobutrol injection

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

GADOBUTROL (UNII: 1BJ477IO2L) (GADOLINIUM CATION (3+) - UNII:AZV954TZ9N)

Available from:

Bayer HealthCare Pharmaceuticals Inc.

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Gadavist 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. Gadavist is indicated for use with MRI in adult patients to assess the presence and extent of malignant breast disease. Gadavist 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. Gadavist 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). Gadavist is contraindicated in patients with history of severe hypersensitivity reactions to Gadavist. 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 Gadavist 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. 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. 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. 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 Gadavist, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. 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 be considered along with the mother’s clinical need for Gadavist and any potential adverse effects on the breastfed infant from Gadavist or from the underlying maternal condition. In lactating rats receiving 0.5 mmol/kg of intravenous [153 Gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk within 3 hours after administration, and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). The safety and effectiveness of Gadavist 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 Gadavist 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 [ see 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 Gadavist 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). No case of NSF associated with Gadavist or any other GBCA has been identified in pediatric patients ages 6 years and younger. Pharmacokinetic studies suggest that clearance of Gadavist 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/1.73m2 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/1.73m2 (age 2 to 7 days), 38 mL/min/1.73m2 (age 8 to 28 days), 62 mL/min/1.73m2 (age 1 to 6 months), and 83 mL/min/1.73m2 (age 6 to 12 months). 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. In clinical studies of Gadavist, 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 Gadavist 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. Prior to administration of Gadavist, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests [see Warnings and Precautions (5.2)] . No dosage adjustment is recommended for patients with renal impairment. Gadavist can be removed from the body by hemodialysis [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)].

Product summary:

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 sizes: 30 mL Pharmacy Bulk Package, rubber stoppered in cartons of 5, Boxes of 10 (NDC 50419-325-14) 65 mL Pharmacy Bulk Package, rubber stoppered, Boxes of 10 (NDC 50419-325-15) 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.

Authorization status:

New Drug Application

Patient Information leaflet

Bayer HealthCare Pharmaceuticals Inc.
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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
dev

Summary of Product characteristics

GADAVIST- GADOBUTROL INJECTION
BAYER HEALTHCARE PHARMACEUTICALS INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
GADAVIST SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR GADAVIST
GADAVIST (GADOBUTROL) INJECTION, FOR INTRAVENOUS USE
PHARMACY BULK PACKAGE
NOT FOR DIRECT INFUSION
INITIAL U.S. APPROVAL: 2011
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE AND NEPHROGENIC SYSTEMIC
FIBROSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
•
•
•
•
RECENT MAJOR CHANGES
Boxed Warning 1/2024
Warnings and Precautions,Risk Associated with Intrathecal Use (5.1)
1/2024
INDICATIONS AND USAGE
Gadavist is a gadolinium-based contrast agent indicated for use with
magnetic resonance imaging (MRI):
•
•
•
•
DOSAGE AND ADMINISTRATION
•
•
•
DOSAGE FORMS AND STRENGTHS
Gadavist injection contains 604.72 mg gadobutrol/mL (equivalent to 1
mmol gadobutrol/mL (3)
CONTRAINDICATIONS
History of severe hypersensitivity reaction to Gadavist (4)
WARNINGS AND PRECAUTIONS
•
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)
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:
CHRONIC, SEVERE KIDNEY DISEASE (GFR < 30 ML/MIN/1.73M ), OR
2
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)
To detect and visualize areas with disrupted blood brain barrier (BBB)