EOVIST- gadoxetate disodium injection, solution

Land: USA

Språk: engelsk

Kilde: NLM (National Library of Medicine)

Aktiv ingrediens:

GADOXETATE DISODIUM (UNII: HOY74VZE0M) (GADOLINIUM CATION (3+) - UNII:AZV954TZ9N)

Tilgjengelig fra:

Bayer HealthCare Pharmaceuticals Inc.

INN (International Name):

GADOXETATE DISODIUM - UNII:AZV954TZ9N)

Sammensetning:

GADOXETATE DISODIUM 181.43 mg in 1 mL

Administreringsrute:

INTRAVENOUS

Resept typen:

PRESCRIPTION DRUG

Indikasjoner:

EOVIST is indicated for intravenous use in magnetic resonance imaging (MRI) of the liver to detect and characterize lesions in patients with known or suspected focal liver disease. EOVIST is contraindicated in patients with history of severe hypersensitivity reactions to EOVIST [see Warnings and Precautions ( 5.3 )] . GBCAs have been shown to 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, no teratogenicity was observed with repeated daily intravenous administration of gadoxetate disodium to rats during organogenesis at doses up to 32 times the recommended single human dose; however, an increase in preimplantation loss was noted at doses 3.2 times the single human dose. Post implantation loss was observed with repeated daily intravenous administration of gadoxetate disodium to rabbits on gestation days 6 through 18 at doses 26 times the recommended single human dose (see Data) . Because of the potential risks of gadolinium to the fetus, use EOVIST only if imaging is essential during pregnancy and cannot be delayed. The background risk in the U.S. general population of major birth defects is 2 to 4% and of miscarriage is 15 to 20% of clinically recognized pregnancies. 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 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, 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. Animal reproductive and developmental toxicity studies were done in rats and rabbits. Gadoxetate disodium was not teratogenic when given intravenously during organogenesis to pregnant rats at doses up to 32 times the recommended single human dose (mmol/m2 basis). However, an increase in preimplantation loss was noted at 3.2 times the human dose (mmol/m2 basis). Compared to untreated controls, rates of postimplantation loss and absorption increased and litter size decreased when pregnant rabbits received gadoxetate disodium at doses 26 times the recommended human single dose (mmol/m2 basis). This occurred without evidence of maternal toxicity. Because pregnant animals received repeated daily doses of gadoxetate disodium, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. Risk Summary There is no information regarding the presence of gadoxetate disodium in human milk, the effects of the drug in a breastfed infant, or the effects of the drug on milk production. However, published lactation data on other GBCAs report that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited GBCA gastrointestinal absorption in the breastfed infant. In rat lactation studies with [153 Gd] gadoxetate disodium, less than 0.5% of the total administered radioactivity was transferred to the nursing pup. Clinical Considerations A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk for up to 10 hours after EOVIST administration in order to minimize exposure to a breastfed infant. Data Animal Data In lactating rats given 0.1 mmol/kg [153 Gd] gadoxetate disodium, less than 0.5% of the total administered radioactivity was transferred to the neonates via maternal milk, mostly within 2 hours. Adequate and well-controlled studies of EOVIST in pediatric patients have not been conducted. An observational study with EOVIST was performed in 52 patients (aged > 2 months and < 18 years) referred for evaluation of suspected or known focal liver lesions. EOVIST improved border delineation and increased contrast of the primary lesion in the majority of patients when compared to non-contrast images. No safety issues were identified. No dose adjustment according to age is necessary in pediatric patients. The safety and effectiveness of EOVIST have not been established in premature infants. NSF Risk No case of NSF associated with EOVIST or any other GBCA has been identified in pediatric patients ages 6 years and younger. 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 EOVIST, 674 (34%) patients were 65 years of age and over, while 20 (1%) were 80 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, use of EOVIST in an elderly patient should be cautious, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy. In a clinical pharmacology study, slight to moderate differences in pharmacokinetic parameters of gadoxetate disodium (increased AUC and terminal half-life, decreased total clearance) were found in a group of geriatric volunteers in comparison to non-geriatric volunteers. No clinically relevant differences in liver contrast enhancement were found. In a clinical pharmacology study in a group of patients with moderate renal impairment, a moderate increase in AUC and terminal half-life was observed in comparison to healthy volunteers with normal renal function. Hepatic contrast did not differ among the groups. End-stage renal failure may impair EOVIST imaging performance [see Warnings and Precautions (5.6)]. In a study of patients with end-stage renal failure, the terminal half-life was prolonged about 12-fold and the AUC was increased about 6-fold. Hepatic contrast was markedly reduced in these patients, which was attributed to significantly elevated serum ferritin levels [see Warnings and Precautions ( 5.2 )] . Approximately 30% of the injected dose was removed by dialysis in a single 3-hour dialysis session, which started one hour after an EOVIST dose. EOVIST was almost completely eliminated via dialysis and biliary excretion within the observation period of 6 days, predominantly within the first 3 days. In a clinical pharmacology study in groups of patients with mild or moderate hepatic impairment, a slight to moderate increase in plasma AUC, half-life and urinary excretion, as well as decrease in hepatobiliary excretion was observed in comparison to healthy subjects with normal liver function. Hepatic contrast signal did not differ among the groups. Severe hepatic impairment may impair EOVIST imaging performance [see Warnings and Precautions (5.6)] . In patients with severe hepatic impairment, especially in patients with abnormally high (> 3 mg/dL) serum bilirubin levels, the AUC was increased up to 60% and the elimination half-life was increased up to 49%. The hepatobiliary excretion substantially decreased to about 5% of the administered dose and reduced hepatic contrast signal was observed. A dose adjustment is not necessary for patients with hepatic impairment. In clinical studies, 489 patients had a diagnosis of liver cirrhosis (Child-Pugh category A, n = 270; category B, n = 98; category C, n = 24; unknown category, n = 97). No difference in diagnostic performance and safety was observed among these patients.

Produkt oppsummering:

EOVIST is supplied in single-dose, rubber stoppered containers (vials) containing 181.43 mg/mL of gadoxetate disodium (equivalent to 0.25 mmol/mL gadoxetate disodium), in the following sizes: 10 mL single-dose containers (vials) filled with 10 mL, boxes of 5 (NDC 50419-320-05) 15 mL single-dose containers (vials) filled with 15 mL, boxes of 5 (NDC 50419-320-15) Store at temperatures between 20° to 25° C (68° to 77° F); excursions permitted to 15° to 30° C (59 to 86) [see USP Controlled Room Temperature] . EOVIST is a ready-to-use solution for single use only. Visually inspect EOVIST for particulate matter and discoloration prior to administration. Do not use the solution if it is discolored or if particulate matter is present. The rubber stopper should not be pierced more than once. Use EOVIST immediately after opening. Unused portions should be discarded.

Autorisasjon status:

New Drug Application

Informasjon til brukeren

Bayer HealthCare Pharmaceuticals Inc.
----------
Medication Guide
EOVIST
(e-o-vist)
(gadoxetate disodium)
Injection for intravenous use
What is Eovist?
•
Eovist is a prescription medicine called a gadolinium-based contrast
agent (GBCA). Eovist, like
other GBCAs, is injected into your vein and used with a magnetic
resonance imaging (MRI)
scanner.
•
An MRI exam with a GBCA, including Eovist, helps your doctor to see
problems better than an
MRI exam without a GBCA. Eovist is needed to better see the problems
in your liver.
•
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 Eovist?
•
GBCAs like EOVIST 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
EOVIST is safe and effective with intrathecal use. EOVIST is not
approved for this use.
•
Eovist 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.
•
At equivalent doses, 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 ca

Preparatomtale

EOVIST- GADOXETATE DISODIUM INJECTION, SOLUTION
BAYER HEALTHCARE PHARMACEUTICALS INC.
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
EOVIST® SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR EOVIST.
EOVIST (GADOXETATE DISODIUM) INJECTION, FOR INTRAVENOUS USE
INITIAL U.S. APPROVAL: 2008
WARNING: RISK ASSOCIATED WITH INTRATHECAL USE AND NEPHROGENIC SYSTEMIC
FIBROSIS
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
•
•
RECENT MAJOR CHANGES
Boxed Warning 1/2024
Warnings and Precautions, Risk Associated with Intrathecal Use
(5.1)1/2024
INDICATIONS AND USAGE
EOVIST is a gadolinium-based contrast agent indicated for use in
magnetic resonance imaging (MRI) of the
liver to detect and characterize lesions in patients with known or
suspected focal liver disease (1)
DOSAGE AND ADMINISTRATION
•
•
•
DOSAGE FORMS AND STRENGTHS
Injection: 181.43 mg/mL in single-dose containers (vials) (3)
CONTRAINDICATIONS
History of severe hypersensitivity reaction to EOVIST (4)
WARNINGS AND PRECAUTIONS
•
•
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥ 0.5%) are nausea,
headache, feeling hot, dizziness, and
back pain (6)
To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare
Pharmaceuticals Inc. at 1-888-84-
INTRATHECAL ADMINISTRATION OF GADOLINIUM-BASED CONTRAST AGENTS (GBCAS)
CAN CAUSE
SERIOUS ADVERSE REACTIONS INCLUDING DEATH, COMA, ENCEPHALOPATHY, AND
SEIZURES.
EOVIST 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 EOVIST 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:
o
o
CHRONIC, SEVERE KIDNEY DISEASE (GFR < 30 ML/MIN/1.73M ), OR
2
ACUTE KIDNEY INJURY.
SCREEN PATIENTS FOR ACUTE KIDNEY INJURY AND OTHER CONDITIONS THAT MAY
REDUCE RENAL
FUNCTION.
FOR PAT