DOTAREM- gadoterate meglumine injection

Quốc gia: Hoa Kỳ

Ngôn ngữ: Tiếng Anh

Nguồn: NLM (National Library of Medicine)

Thành phần hoạt chất:

gadoterate meglumine (UNII: L0ND3981AG) (GADOLINIUM CATION (3+) - UNII:AZV954TZ9N)

Sẵn có từ:

Guerbet LLC

INN (Tên quốc tế):

gadoterate meglumine - UNII:AZV954TZ9N)

Thành phần:

GADOLINIUM CATION (3+) 376.9 mg in 1 mL

Tuyến hành chính:

Intravenous

Loại thuốc theo toa:

PRESCRIPTION DRUG

Chỉ dẫn điều trị:

DOTAREM 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 DOTAREM [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 of 16 and 10 times, respectively, the recommended human dose (see Data ). Because of the potential risks of gadolinium to the fetus, use DOTAREM 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 on 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 present in breast milk. Additionally, there is limited GBCA gastrointestinal absorption in the breast-fed 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 DOTAREM and any potential adverse effects on the breastfed infant from DOTAREM or from the underlying maternal condition. Data Nonclinical data demonstrate that gadoterate is detected in goat milk in amounts of < 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 DOTAREM 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 dose adjustment according to age is necessary in pediatric patients [see Dosage and Administration (2.1), Pharmacokinetics (12.3)] . The safety of DOTAREM has not been established in preterm neonates. No cases of NSF associated with DOTAREM or any other GBCA have been identified in pediatric patients age 6 years and younger [see Warnings and Precautions (5.2)] . Normal estimated GFR (eGFR) is approximately 30 mL/minute/1.73m2 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 DOTAREM, 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 DOTAREM 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 DOTAREM dosage adjustment is recommended for patients with renal impairment. Gadoterate can be removed from the body by hemodialysis [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)] .

Tóm tắt sản phẩm:

DOTAREM Injection is a clear, colorless to yellow solution containing 0.5 mmol/mL of gadoterate meglumine. Each Pharmacy Bulk Package vial is closed with a rubber stopper and sealed with an aluminum cap and the contents are sterile. DOTAREM Pharmacy Bulk Package is packaged in a shrink wrapped package of 6, in the following configurations: 100 mL in glass vial (NDC 67684-2000-4) DOTAREM Pharmacy Bulk Package is also packaged in a box of 6, in the following configurations: 100 mL in glass vial (NDC 67684-2001-4) 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 (CRT)]. Should solidification occur in the vial because of exposure to the cold, bring DOTAREM to room temperature before use. If allowed to stand at room temperature for a minimum of 90 minutes, DOTAREM 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.

Tình trạng ủy quyền:

New Drug Application

Tờ rơi thông tin

Guerbet LLC
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MEDICATION GUIDE
DOTAREM® (doh TAH rem)
(gadoterate meglumine)
Injection for intravenous use
What is DOTAREM?
•
DOTAREM is a prescription medicine called a gadolinium-based
contrast agent (GBCA). DOTAREM, like other GBCAs, is injected
into your vein and used with a magnetic resonance imaging (MRI)
scanner.
•
An MRI exam with a GBCA, including DOTAREM, 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 DOTAREM?
•
GBCAs like DOTAREM 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
DOTAREM is safe and effective with intrathecal use. DOTAREM is
not approved for this use.
•
DOTAREM 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
develop a condition with seve

Đặc tính sản phẩm

DOTAREM- GADOTERATE MEGLUMINE INJECTION
GUERBET LLC
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
DOTAREM SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR DOTAREM.
DOTAREM (GADOTERATE MEGLUMINE) INJECTION FOR INTRAVENOUS USE
PHARMACY BULK PACKAGE
NOT FOR DIRECT INFUSION
INITIAL U.S. APPROVAL: 2013
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.
DOTAREM 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 DOTAREM 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 (5.2)
RECENT MAJOR CHANGES
Boxed Warning 1/2024
Warnings and Precautions, Risk Associated with Intrathecal Use (5.1)
1/2024
INDICATIONS AND USAGE
DOTAREM 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 DOTAREM is 0.2
mL/kg (0.1 mmol/kg) body weight
administered as an