CLARISCAN- gadoterate meglumine injection, solution

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

GADOTERATE MEGLUMINE (UNII: L0ND3981AG) (GADOLINIUM CATION (3+) - UNII:AZV954TZ9N)

Available from:

GE Healthcare

Administration route:

INTRAVENOUS

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Clariscan is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity. History of clinically important hypersensitivity reactions to Clariscan [see Warnings and Precautions (5.2)]. Risk Summary GBCAs cross the human 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, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadoterate meglumine during organogenesis at doses up to 16 and 10 times, respectively, the recommended human dose (see Data) . Because of the potential risks of gadolinium to the fetus, use Clariscan 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(s) are 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 2-4% and 15-20%, 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 material 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 Gadoterate meglumine was administered in intravenous doses of 0, 2, 4 and 10 mmol/kg/day [3, 7 and 16 times the recommended human dose (RHD) based on body surface area (BSA)] to female rats for 14 days before mating, throughout the mating period and until gestation day (GD) 17. Pregnant rabbits were administered gadoterate meglumine in intravenous doses of 0, 1, 3 and 7 mmol/kg/day (3, 10 and 23 times the RHD based on BSA) from GD6 to GD19. No effects on embryo-fetal development were observed at doses up to 10 mmol/kg/day in rats and 3 mmol/kg/day in rabbits. Maternal toxicity was observed in rats at 10 mmol/kg/day and in rabbits at 7 mmol/kg/day. This maternal toxicity was characterized in rats by a slightly lower litter size and gravid uterus weight compared to the control group, and in rabbits by a reduction in body weight and food consumption. Risk Summary There are no data on the presence of gadoterate 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 excreted in breast milk. Additionally, there is limited GBCA gastrointestinal absorption in the breastfed infant. Gadoterate is present in goat milk (see Data ). The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Clariscan and any potential adverse effects on the breastfed infant from Clariscan or from the underlying maternal condition. Data Nonclinical data demonstrate that gadoterate is detected in goat milk in amounts < 0.1% of the dose intravenously administered. Furthermore, in rats, absorption of gadoterate via the gastrointestinal tract is poor (1.2% of the administered dose was absorbed and eliminated in urine). The safety and efficacy of gadoterate meglumine at a single dose of 0.1 mmol/kg have been established in pediatric patients from birth (term neonates ≥ 37 weeks gestational age) to 17 years of age based on clinical data in 133 pediatric patients 2 years of age and older, and clinical data in 52 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 dosage adjustment according to age is necessary in pediatric patients [See Dosage and Administration (2.1), Pharmacokinetics (12.3)] . The safety of gadoterate meglumine has not been established in preterm neonates. No cases of NSF associated with gadoterate meglumine or any other GBCA have been identified in pediatric patients age 6 years and younger [see Warnings and Precautions (5.1)] . Normal estimated GFR (eGFR) is approximately 30 mL/minute/1.73 m2 at birth and increases to adult values by 2 years of age. Juvenile Animal Data 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 gadoterate meglumine, 900 patients were 65 years of age and over, and 304 patients were 75 years of age and over. No overall differences in safety or efficacy were observed between these subjects and younger subjects. In general, use of Clariscan in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. No age-related dosage adjustment is necessary. No Clariscan dosage adjustment is recommended for patients with renal impairment. Gadoterate meglumine can be removed from the body by hemodialysis [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3)].

Product summary:

Clariscan Injection is a clear, colorless to yellow solution containing 0.5 mmol/mL of gadoterate meglumine. It is supplied in vials and pre-filled syringes. Each single-dose vial is closed with a rubber stopper and sealed with an aluminum cap and the contents are sterile. Vials are packaged in a box of 10, in the following configurations: Each syringe is sealed with rubber closures and the contents are sterile. Syringes, including plunger rod, are individually packaged in a box of 10, in the following configurations: Storage Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP, Controlled Room Temperature]. Pre-filled syringes must not be frozen. Frozen syringes should be discarded. Should solidification occur in the vial because of exposure to the cold, bring Clariscan to room temperature before use. If allowed to stand at room temperature for a minimum of 90 minutes, Clariscan should return to a clear, colorless to yellow solution. Before use, examine the product to assure that all solids are dissolved and that the container and closure have not been damaged. Discard the vial if solids persist.

Authorization status:

Abbreviated New Drug Application

Patient Information leaflet

GE Healthcare
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MEDICATION GUIDE
CLARISCAN™ (kla-ri'-skan)
(gadoterate meglumine)
injection for intravenous use
What is Clariscan?
•
Clariscan is a prescription medicine called a gadolinium-based
contrast agent (GBCA). Clariscan,
like other GBCAs, is injected into your vein and used with a magnetic
resonance imaging (MRI)
scanner.
•
An MRI exam with a GBCA, including Clariscan, 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 Clariscan?
•
Clariscan 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 Clariscan, 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 Clariscan.
Do not receive Clariscan if you have had a seve

Summary of Product characteristics

CLARISCAN- GADOTERATE MEGLUMINE INJECTION, SOLUTION
GE HEALTHCARE
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
CLARISCAN SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR CLARISCAN.
CLARISCAN™ (GADOTERATE MEGLUMINE) INJECTION FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2013
WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING_
GADOLINIUM-BASED CONTRAST AGENTS (GBCAS) INCREASE THE RISK FOR NSF
AMONG PATIENTS
WITH IMPAIRED ELIMINATION OF THE DRUGS. AVOID USE OF GBCAS 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/1.73 M ), 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
(FOR EXAMPLE,
AGE > 60 YEARS, HYPERTENSION OR DIABETES), ESTIMATE THE GLOMERULAR
FILTRATION RATE
(GFR) THROUGH LABORATORY TESTING (5.1).
INDICATIONS AND USAGE
Clariscan is a gadolinium-based contrast agent indicated for
intravenous use with magnetic resonance
imaging (MRI) in brain (intracranial), spine and associated tissues in
adult and pediatric patients (including
term neonates) to detect and visualize areas with disruption of the
blood brain barrier (BBB) and/or
abnormal vascularity. (1)
DOSAGE AND ADMINISTRATION
Adult and pediatric patients: The recommended dose of Clariscan is 0.2
mL/kg (0.1 mmol/kg) body weight
administered as an intravenous bolus injection at a flow rate of
approximately 2 mL/second for adults and
1-2 mL/second for pediatric patients (including term neonates). The
dose is delivered by manual or power
injection. (2)
DOSAGE FORMS AND STRENGTHS
Clariscan Injection 0.5 mmol/mL contains 376.9 mg/mL of gadoterate
meglumine and is available in vials
and pre-filled syringes. (3)
CONTRAINDICATI