Prohance Prescribing Information
contrast agents (GBCAs) can cause serious adverse reactions including
death, coma, encephalopathy, and seizures. ProHance is not approved
for intrathecal use
Intrathecal administration of GBCAs can
cause serious adverse reactions including death, coma, encephalopathy,
and seizures. The safety and effectiveness of ProHance have not been
established with intrathecal use. ProHance is not approved for intrathecal
use
systemic fibrosis (NSF) among patients with impaired elimination of
the drugs. Avoid use of ProHance 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 less than 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 greater than 60 years, hypertension or diabetes), estimate
the glomerular filtration rate (GFR) through laboratory testing.
at highest risk for NSF, do not exceed the recommended ProHance dose
and allow a sufficient period of time for elimination of the drug
from the body prior to re-administration
Precautions (
Fibrosis
GCBAs increase the
risk for nephrogenic systemic fibrosis (NSF) among patients with impaired
elimination of the drugs. Avoid use of ProHance 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
less than 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
ProHance 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 (for example,
age greater than 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
ProHance 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.
ProHance
is a gadolinium-based contrast agent indicated for magnetic resonance
imaging (MRI) to visualize:
- lesions with disrupted blood brain barrier and/or abnormal
vascularity in the brain (intracranial lesions), spine and associated
tissues in adults and pediatric patients, including term neonates ()1.1 MRI of the Central
Nervous System (CNS)ProHance is indicated
for magnetic resonance imaging (MRI) in adults and pediatric patients
including term neonates to visualize lesions with disrupted blood
brain barrier and/or abnormal vascularity in the brain (intracranial
lesions), spine and associated tissues. - lesions in the head and neck in adults ()
1.2 MRI of Extracranial/Extraspinal
Head and NeckProHance is indicated for MRI in adults to visualize lesions in the
head and neck.
- Recommended dose in adult and pediatric patients is 0.2
mL/kg (0.1 mmol/kg) body weight administered as rapid intravenous
infusion or bolus ()2.1 Recommended DoseThe recommended dose for adult
and pediatric patients, including term neonates, is 0.2 mL/kg (0.1
mmol/kg) administered as a rapid intravenous infusion (10 mL/min to
60 mL/min) or bolus (greater than 60 mL/min). Table 1 provides weight-adjusted
recommended dose volumes.Table 1: Recommended
Volume of ProHance Injection by Body WeightBody Weight (kg)Volume to be Administered
(mL)2.5 0.5 5 1 10 2 20 4 30 6 40 8 50 10 60 12 70 14 80 16 90 18 100 20 110 22 120 24 130 26 140 28 150 30 MRI:
of the CNS in Adults- A supplementary dose of 0.4 mL/kg (0.2 mmol/kg) may be given
up to 30 minutes after the first dose in adult patients with normal
renal function suspected of having poorly visualized CNS lesions,
in the presence of negative or equivocal scans - The safety and efficacy of supplementary dosing have not
been established in pediatric patients
- A supplementary dose of 0.4 mL/kg (0.2 mmol/kg) may be given
- Follow injection with a saline flush of at least 5 mL normal
saline ()2.1 Recommended DoseThe recommended dose for adult
and pediatric patients, including term neonates, is 0.2 mL/kg (0.1
mmol/kg) administered as a rapid intravenous infusion (10 mL/min to
60 mL/min) or bolus (greater than 60 mL/min). Table 1 provides weight-adjusted
recommended dose volumes.Table 1: Recommended
Volume of ProHance Injection by Body WeightBody Weight (kg)Volume to be Administered
(mL)2.5 0.5 5 1 10 2 20 4 30 6 40 8 50 10 60 12 70 14 80 16 90 18 100 20 110 22 120 24 130 26 140 28 150 30 MRI:
of the CNS in Adults- A supplementary dose of 0.4 mL/kg (0.2 mmol/kg) may be given
up to 30 minutes after the first dose in adult patients with normal
renal function suspected of having poorly visualized CNS lesions,
in the presence of negative or equivocal scans - The safety and efficacy of supplementary dosing have not
been established in pediatric patients
- A supplementary dose of 0.4 mL/kg (0.2 mmol/kg) may be given
ProHance
is supplied as a sterile, non-pyrogenic, and colorless to slightly
yellow solution available in single-dose vials or prefilled syringes.
Each mL contains 279.3 mg (0.5 mmol/mL) of gadoteridol for injection.
Pregnancy: Use only if imaging
is essential during pregnancy and cannot be delayed. (
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). Because of the potential risks of gadolinium
to the fetus, use ProHance only if imaging is essential during pregnancy
and cannot be delayed.
In animal reproduction
studies in rats, gadoteridol doubled the incidence of post-implantation
loss at up to 16 times the recommended human dose (RHD). There were
no adverse developmental effects observed in rabbits with intravenous
administration of gadoteridol during organogenesis at doses up to
19 times the recommended human dose of 0.1 mmol/kg
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 agent 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.
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
Gadoteridol was administered in intravenous doses of 0, 0.375, 1.5,
6.0, and 10 mmol/kg/day [0.6, 2.4, 9.7, and 16 times the recommended
human dose (RHD) based on body surface area (BSA)] to female rats
from gestational day (GD)6 until GD17. Gadoteridol at 10 mmol/kg/day
for 12 days during gestation doubled the incidence of post-implantation
loss. When rats were administered 6.0 or 10.0 mmol/kg/day for 12 days,
an increase in spontaneous locomotor activity was observed in the
offspring. Pregnant rabbits were administered gadoteridol in intravenous
doses of 0, 0.4, 1.5, and 6 mmol/kg/day (1.3, 4.8, and 19.4 times
the RHD based on BSA) from GD6 to GD18. Gadoteridol increased the
incidence of spontaneous abortion and early delivery in rabbits administered
6 mmol/kg/day for 13 days during gestation.
ProHance is contraindicated
in patients with known allergic or hypersensitivity reactions to ProHance
Reactions
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 ProHance administration
and resolved with prompt emergency treatment.
Prior to ProHance administration, ensure
the availability of trained personnel and medications to treat hypersensitivity
reactions. Consider the risk for hypersensitivity reactions, especially
in patients with a history of hypersensitivity reactions or a history
of asthma or other allergic disorders. If such a reaction occurs,
stop ProHance and immediately begin appropriate therapy. Observe patients
for signs and symptoms of a hypersensitivity reaction during and for
up to 2 hours after ProHance administration.