Gadavist Prescribing Information
Intrathecal administration of gadolinium-based contrast agents (GBCAs) can cause serious adverse reactions including death, coma, encephalopathy, and seizures. Gadavist is not approved for intrathecal use
GBCAs increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of Gadavist 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 fibrosis affecting the skin, muscle and internal organs.
The risk for NSF appears highest among patients with:
• Chronic, severe kidney disease (GFR < 30 mL/min/1.73m2), 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.
For patients at highest risk for NSF, do not exceed the recommended Gadavist dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration
Warnings and Precautions, Acute Respiratory Distress Syndrome (5.4) 3/2025
Gadavist is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI):
• To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates ()1.1 Magnetic Resonance Imaging (MRI) of the Central Nervous System (CNS)Gadavist is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.
• To assess the presence and extent of malignant breast disease in adult patients ()1.2 MRI of the BreastGadavist is indicated for use with MRI in adult patients to assess the presence and extent of malignant breast disease.
• To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates ()1.3 Magnetic Resonance Angiography (MRA)Gadavist is indicated for use in magnetic resonance angiography (MRA) in adult and pediatric patients, including term neonates, to evaluate known or suspected supra-aortic or renal artery disease.• To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD). ().1.4 Cardiac MRIGadavist is indicated for use in cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).
• Recommended dose for adults and pediatric patients (including term neonates) is 0.1 mL/kg body weight ()2.1 Recommended DoseThe recommended dose of Gadavist for adult and pediatric patients (including term neonates) is 0.1 mL/kg body weight (0.1 mmol/kg). Refer to Table 1 to determine the volume to be administered.
Table 1: Volume of Gadavist Injection by Body Weight* Body Weight (kg)Volume to be Administered (mL)2.5
0.25
5
0.5
10
1
15
1.5
20
2
25
2.5
30
3
35
3.5
40
4
45
4.5
50
5
60
6
70
7
80
8
90
9
100
10
110
11
120
12
130
13
140
14
*for
Cardiac MRI, the dose is divided into 2 separate, equal injections• Administer as an intravenous bolus injection ()2.2 Administration Guidelines• Gadavist is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration. Use Table 1 to determine the volume to be administered.• Use sterile technique when preparing and administering Gadavist.
MRI of the Central Nervous System• Administer Gadavist as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second.• Follow Gadavist injection with a normal saline flush to ensure complete administration of the contrast.• Post contrast MRI can commence immediately following contrast administration.
MRI of the Breast• Administer Gadavist as an intravenous bolus by power injector, followed by a normal saline flush to ensure complete administration of the contrast.• Start image acquisition following contrast administration and then repeat sequentially to determine peak intensity and wash-out.
MR AngiographyImage acquisition should coincide with peak arterial concentration, which varies among patients.Adults• Administer Gadavist by power injector, at a flow rate of approximately 1.5 mL/second, followed by a 30 mL normal saline flush at the same rate to ensure complete administration of the contrast.
Pediatric patients• Administer Gadavist by power injector or manually, followed by a normal saline flush to ensure complete administration of the contrast.
Cardiac MRI• Administer Gadavist through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent.• Administer Gadavist as two (2) separate bolus injections: 0.05 mL/kg (0.05 mmol/kg) body weight at peak pharmacologic stress followed by 0.05 mL/kg (0.05 mmol/kg) body weight at rest.• Administer Gadavist via a power injector at a flow rate of approximately 4 mL/second and follow each injection with a normal saline flush of 20 mL at the same flow rate.
• Follow injection with a normal saline flush ()2.2 Administration Guidelines• Gadavist is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium based contrast agents, resulting in a lower volume of administration. Use Table 1 to determine the volume to be administered.• Use sterile technique when preparing and administering Gadavist.
MRI of the Central Nervous System• Administer Gadavist as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second.• Follow Gadavist injection with a normal saline flush to ensure complete administration of the contrast.• Post contrast MRI can commence immediately following contrast administration.
MRI of the Breast• Administer Gadavist as an intravenous bolus by power injector, followed by a normal saline flush to ensure complete administration of the contrast.• Start image acquisition following contrast administration and then repeat sequentially to determine peak intensity and wash-out.
MR AngiographyImage acquisition should coincide with peak arterial concentration, which varies among patients.Adults• Administer Gadavist by power injector, at a flow rate of approximately 1.5 mL/second, followed by a 30 mL normal saline flush at the same rate to ensure complete administration of the contrast.
Pediatric patients• Administer Gadavist by power injector or manually, followed by a normal saline flush to ensure complete administration of the contrast.
Cardiac MRI• Administer Gadavist through a separate intravenous line in the contralateral arm if concomitantly providing a continuous infusion of a pharmacologic stress agent.• Administer Gadavist as two (2) separate bolus injections: 0.05 mL/kg (0.05 mmol/kg) body weight at peak pharmacologic stress followed by 0.05 mL/kg (0.05 mmol/kg) body weight at rest.• Administer Gadavist via a power injector at a flow rate of approximately 4 mL/second and follow each injection with a normal saline flush of 20 mL at the same flow rate.
Gadavist is a sterile, clear, and colorless to pale yellow solution for injection containing 604.72 mg gadobutrol per mL (equivalent to 1 mmol gadobutrol/mL) supplied in single-dose vials and pre-filled disposable syringes.
8.1 PregnancyGBCAs 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
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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.
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 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 DataGadolinium RetentionGBCAs 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 ToxicologyEmbryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. Embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). In rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses).
Because pregnant animals received repeated daily doses of Gadavist, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans