Multihance Prescribing Information
contrast agents (GBCAs) can cause serious adverse reactions including
death, coma, encephalopathy, and seizures. MultiHance is not approved
for intrathecal use
with Intrathecal Use
Intrathecal administration of GBCAs can
cause serious adverse reactions including death, coma, encephalopathy,
and seizures. The safety and effectiveness of MultiHance have not
been established with intrathecal use. MultiHance is not approved
for intrathecal use
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-contrasted MRI
or other modalities. NSF may result in fatal or debilitating systemic
fibrosis affecting the skin, muscle and internal organs.
highest among patients with:
- chronic, severe kidney disease (GFR <30 mL/min/1.73m2), or
- acute kidney injury.
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.
risk for NSF, do not exceed the recommended MultiHance dose and allow
a sufficient period of time for elimination of the drug from the body
prior to re-administration
Fibrosis
GBCAs increase
the risk for nephrogenic systemic fibrosis (NSF) among patients with
impaired elimination of the drugs. Avoid use of MultiHance among these
patients unless the diagnostic information is essential and not available
with non-contrast enhanced MRI or other modalities. The GBCA-associated
NSF risk appears highest for patients with chronic, severe kidney
disease (GFR <30 mL/min/1.73m2) as well
as patients with acute kidney injury. The risk appears lower for patients
with chronic, moderate kidney disease (GFR 30-59 mL/min/1.73m2) and little, if any, for patients with chronic, mild
kidney disease (GFR 60-89 mL/min/1.73m2). NSF may result in fatal or debilitating fibrosis affecting the
skin, muscle and internal organs. Report any diagnosis of NSF following
MultiHance administration to Bracco Diagnostics (1-800-257-5181) or
FDA (1-800-FDA-1088 or
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 (e.g., 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 the 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 MultiHance dose and allow a sufficient period of time
for elimination of the drug prior to re-administration. For patients
receiving hemodialysis, physicians may consider the prompt initiation
of hemodialysis following the administration of a GBCA in order to
enhance the contrast agent’s elimination. The usefulness of hemodialysis
in the prevention of NSF is unknown [
- 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
Imaging (MRI) of the Central Nervous System (CNS)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. - magnetic resonance angiography (MRA) to evaluate adults
with known or suspected renal or aorto-ilio-femoral occlusive vascular
disease.1.2 Magnetic Resonance
Angiography (MRA) of Renal and Aorto-ilio-femoral VesselsMultiHance is indicated for use in magnetic
resonance angiography (MRA) to evaluate adults with known or suspected
renal or aorto-ilio-femoral occlusive vascular disease.
- The recommended dose of MultiHance is 0.2 mL/kg (0.1 mmol/kg)
administered as a rapid bolus intravenous injection. - For MRI of the CNS in pediatric patients below 2 years of
age the recommended dosage range is 0.1 to 0.2 mL/kg. - To ensure complete injection of the contrast medium, follow
the injection with a saline flush of at least 5 mL in MRI of the CNS
and at least 20 mL in MRA. ()2 DOSAGE AND ADMINISTRATION- The recommended dose of MultiHance is 0.2 mL/kg (0.1 mmol/kg)
administered as a rapid bolus intravenous injection. - For MRI of the CNS in pediatric patients below 2 years of
age the recommended dosage range is 0.1 to 0.2 mL/kg. - To ensure complete injection of the contrast medium, follow
the injection with a saline flush of at least 5 mL in MRI of the CNS
and at least 20 mL in MRA.
2.1 Dosing and Imaging Instructions2.1.1 MRI of the CNSIn adults and in pediatric patients over
2 years of age, the recommended dose of MultiHance for MRI of the
CNS is 0.2 mL/kg (0.1 mmol/kg) administered as a rapid bolus intravenous
injection. In pediatric patients below 2 years of age, the recommended
dosage range is 0.1 to 0.2 mL/kg administered as a rapid bolus intravenous
injection. To ensure complete injection of the contrast medium, follow
the injection with a saline flush of at least 5 mL. Imaging of the
CNS can be performed starting immediately after the bolus injection
of MultiHance.2.1.2 MRA of Renal and
Aorto-ilio-femoral VesselsFor MRA examination, the recommended dose is 0.2 mL/kg (0.1 mmol/kg)
administered as a rapid bolus intravenous injection followed by at
least 20 mL saline flush either manually or using an automatic injector
system. Start imaging immediately after the administration of MultiHance,
with scan delay calculated by test bolus or automatic bolus detection
technique. If an automatic contrast detection pulse sequence is not
used for bolus timing, then a test bolus injection of 1-2 mL of MultiHance
should be used to calculate the appropriate scan delay.2.2 Dosing Table*For pediatric patients
less than 2 years of age, one-half of the per kg dose may be used.TABLE 1: WEIGHT-BASED DOSING VOLUMES FOR:
CNS IMAGING
(ADULTS AND PEDIATRICS ≥2 YEARS OF AGE*)
AND
MRA IMAGING (ADULTS ONLY)0.1mM/kg dose Kilograms (Kg) Pounds (lb) Volume, Milliliters
(mL)2.5 5.5 0.5 5 11 1.0 10 22 2.0 15 33 3.0 20 44 4.0 25 55 5.0 30 66 6.0 35 77 7.0 40 88 8.0 45 99 9.0 50 110 10.0 55 121 11.0 60 132 12.0 65 143 13.0 70 154 14.0 75 165 15.0 80 176 16.0 85 187 17.0 90 198 18.0 95 209 19.0 100 220 20.0 105 231 21.0 110 242 22.0 115 253 23.0 120 264 24.0 125 275 25.0 130 286 26.0 135 297 27.0 140 308 28.0 145 319 29.0 150 330 30.0 2.3 AdministrationInspect the MultiHance vial visually for
particulate matter and discoloration prior to administration. Do not
use the solution if it is discolored or particulate matter is present.
Draw MultiHance into a syringe and inject using sterile technique.Do not mix intravenous medications or
parenteral nutrition solutions with MultiHance. Do not administer
other medications in the same intravenous line with MultiHance.MultiHance vials are intended for single
use only. Administer immediately after opening and discard any unused
product. - The recommended dose of MultiHance is 0.2 mL/kg (0.1 mmol/kg)
MultiHance is a sterile, nonpyrogenic, clear,
colorless to slightly yellow aqueous solution for intravenous use
only, containing 529 mg gadobenate dimeglumine per mL.
Pregnancy: Use only if imaging
is essential during pregnancy and cannot be delayed. (
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 (
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
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.
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.
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.
MultiHance is contraindicated in patients with known allergic or
hypersensitivity reactions to gadolinium-based contrast agents [
Anaphylactic and anaphylactoid reactions have been reported,
involving cardiovascular, respiratory, and/or cutaneous manifestations.
Some patients experienced circulatory collapse and died. In most
cases, initial symptoms occurred within minutes of MultiHance administration
and resolved with prompt emergency treatment.
Prior to MultiHance administration, ensure the availability
of personnel trained and medications to treat hypersensitivity reactions.
If such a reaction occurs stop MultiHance and immediately begin appropriate
therapy. Additionally, consider the risk for hypersensitivity reactions,
especially in patients with a history of hypersensitivity reactions
or a history of asthma or other allergic disorders. Observe patients
for signs and symptoms of a hypersensitivity reaction during and for
up to 2 hours after MultiHance administration.