MULTIHANCE- gadobenate dimeglumine injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

gadobenate dimeglumine (UNII: 3Q6PPC19PO) (GADOLINIUM CATION (3+) - UNII:AZV954TZ9N)

Available from:

BRACCO DIAGNOSTICS INC

INN (International Name):

gadobenate dimeglumine - UNII:AZV954TZ9N)

Composition:

gadobenate dimeglumine 529 mg in 1 mL

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

MultiHance is indicated for intravenous use in magnetic resonance imaging (MRI) of the central nervous system (CNS) in adults and pediatric patients (including term neonates), to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. MultiHance is indicated for use in magnetic resonance angiography (MRA) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease. MultiHance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents [see Warnings and Precautions (5.3)] . 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, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to 6 times the recommended human dose. There were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose (see Data) . Because of the potential risks of gadolinium to the fetus, use MultiHance only if imaging is essential and cannot be delayed. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, 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 Gadobenate dimeglumine has been shown to be teratogenic in rabbits when administered intravenously at 2 mmol/kg/day (6 times the recommended human dose based on body surface area) during organogenesis (day 6 to 18) inducing microphthalmia/small eye and/or focal retinal fold in 3 fetuses from 3 separate litters. In addition, MultiHance administered intravenously at 3 mmol/kg/day (10 times the recommended human dose based on body surface area) has been shown to increase intrauterine deaths in rabbits. There was no evidence that MultiHance induced teratogenic effects in rats at doses up to 2 mmol/kg/day (3 times the recommended human dose based on body surface area), however, rat dams exhibited no systemic toxicity at this dose. There were no adverse effects on the birth, survival, growth, development and fertility of the F1 generation at doses up to 2 mmol/kg in a rat peri- and post-natal (Segment III) study. Risk Summary Limited literature reports that breastfeeding after gadobenate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose. There is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. Additionally, there is limited GBCA gastrointestinal absorption. The developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for MultiHance and any potential adverse effects on the breastfed infant from MultiHance or from the underlying maternal condition. MultiHance is approved for intravenous use for MRI of the CNS to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to less than 17 years of age. Pediatric use is based on evidence of effectiveness in adults and in 202 pediatric patients 2 years of age and older, in addition to experience in 105 pediatric patients birth to less than 2 years of age that supported extrapolation from adult data [see Clinical Studies (14)] . Adverse reactions in pediatric patients were similar to those reported in adults [see Adverse Reactions (6.1)] . No dose adjustment according to age is necessary in pediatric patients two years of age and older. For pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 mL/kg [see Dosage and Administration (2.1), Pharmacokinetics (12.3)] . The safety of MultiHance has not been established in preterm neonates. Of the total number of 4967 adult subjects in clinical studies of MultiHance, 33% were 65 or older. No overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. The drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to MultiHance may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function it may be useful to monitor renal function.

Product summary:

16.1  How Supplied MultiHance Multipack (gadobenate dimeglumine) injection is a clear, colorless to slightly yellow solution containing 529 mg gadobenate dimeglumine per mL. MultiHance Multipack is supplied in glass bottles; each multidose bottle is rubber stoppered with an aluminum seal and the contents are sterile. MultiHance is supplied in boxes of: Five 50 mL Pharmacy Bulk Packages           (NDC 0270-5264-16) Five 100 mL Pharmacy Bulk Packages         (NDC 0270-5264-17) 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]. Do not freeze.

Authorization status:

New Drug Application

Patient Information leaflet

BRACCO DIAGNOSTICS INC
----------
This Medication Guide has been approved by the U.S. Food and Drug
Administration
Issued 01/2024
COEB404
MEDICATION GUIDE
MULTIHANCE (məl-tē-han(t)s)
(gadobenate dimeglumine)
Injection for intravenous use
What is MULTIHANCE?
•
MULTIHANCE is a prescription medicine called a gadolinium-based
contrast agent (GBCA).
MULTIHANCE, like other GBCAs, is injected into your vein and used with
a magnetic
resonance imaging (MRI) scanner.
•
An MRI exam with a GBCA, including MULTIHANCE, 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 MULTIHANCE?
•
GBCAs like MULTIHANCE may cause serious side effects including death,
coma,
encephalopathy, and seizures when it is given intrathecally (injection
given into the spinal cord).
It is not known if MULTIHANCE is safe and effective with intrathecal
use. MULTIHANCE is
not approved for this use.
•
MULTIHANCE 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

Summary of Product characteristics

MULTIHANCE- GADOBENATE DIMEGLUMINE INJECTION, SOLUTION
BRACCO DIAGNOSTICS INC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
MULTIHANCE SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR MULTIHANCE.
MULTIHANCE (GADOBENATE DIMEGLUMINE) INJECTION
INITIAL U.S. APPROVAL: 2004
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.
MULTIHANCE 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 MULTIHANCE IN
THESE PATIENTS
UNLESS THE DIAGNOSTIC INFORMATION IS ESSENTIAL AND NOT AVAILABLE WITH
NON-CONTRAST
MRI OR OTHER MODALITIES. THE RISK FOR NSF APPEARS HIGHEST AMONG
PATIENTS WITH:
CHRONIC, SEVERE KIDNEY DISEASE (GFR <30 ML/MIN/1.73M ), OR
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
(E.G. AGE >60
YEARS, HYPERTENSION OR DIABETES), ESTIMATE THE GLOMERULAR FILTRATION
RATE (GFR)
THROUGH LABORATORY TESTING. (5.2)
RECENT MAJOR CHANGES
Boxed Warning
1/2024
Warnings and Precautions, Risk Associated with Intrathecal Use(5.1)
1/2024
INDICATIONS AND USAGE
magnetic resonance imaging (MRI) of the central nervous system (CNS)
in adults and pediatric patients
(including term neonates), to visualize lesions with abnormal
blood-brain barrier or abnormal vascularity
of the brain, spine, and associated tissues (1.1)
magnetic resonance angiography (MRA) to evaluate adults with known or
suspected renal or aorto-ilio-
femoral occlusive vascular disease. (1.2)
DOSAGE AND ADMINISTRATION
PHARMACY BULK PACKAGE – NOT FOR DIRECT INFUSION
The recommended dose of MultiHance is 0.2