Gadavist

MRI Agents

 
NOTE: Hypersensitivity reactions may occur. Prior to administration, assess all patients for previous reactions to contrast media. Trained personnel and therapies used to treat hypersensitivity reactions (epinephrine, antihistamines, and corticosteroids) should be readily available. Observe patient for signs and symptoms of hypersensitivity reactions during and after administration.

Visually inspect for particulate matter and discoloration prior to administration. Solution is clear, colorless to pale yellow. Do not use if discolored or if particulate matter is present.
Do not mix with other medications. Do not administer other medications in the same intravenous line.

Use aseptic technique when preparing and administering gadobutrol.
Ensure catheter and venous patency before the injection. Extravasation may result in tissue irritation.[59653]
 
Single-dose vials
Draw gadobutrol into the syringe immediately before use.
Do not pierce the rubber stopper more than once.
Storage: The product contains no antimicrobial preservatives. Discard any unused vial contents.[59653]
 
Prefilled syringes
Remove tip cap immediately before use.
Storage: The product contains no antimicrobial preservatives. Discard any unused syringe contents.[59653]
 
Bulk package
The bulk package contains many single doses of gadobutrol. It is for intravenous use and not for direct infusion.
Use the bulk package only with an automated contrast injection system, contrast management system, or contrast media transfer set approved or cleared for use with gadobutrol.
The bulk package is to be used only in a room designated for radiological procedures that involve intravascular administration of a contrast agent.
Penetrate the container closure only once with a suitable sterile component of the automated contrast injection system, contrast management system, or contrast transfer set (e.g., transfer spike).
Once punctured, do not remove the bulk package from the work area during the entire period of use. If the integrity of the bulk package and the delivery system cannot be assured through direct continuous supervision, discard the bulk package and all associated disposables for the automated contrast injection system, contrast management system, or contrast media transfer set.
Storage: After the container closure has been entered, store the bulk package between 20 to 25 degrees C (68 to 77 degrees F). A maximum use time of 24 hours from the initial puncture is permitted to complete fluid transfer. Discard any unused product 24 hours after the initial puncture.[65772]
 
Cardiac MRI
Administer total dose via 2 separate, equal IV injections by power injector at a flow rate of approximately 4 mL/second. Give the first injection during peak pharmacologic stress and second injection at rest.
Follow each injection with a 20 mL 0.9% Sodium Chloride Injection flush, at a flow rate of approximately 4 mL/second.
If concomitantly administering a continuous infusion of a pharmacologic stress agent, administer gadobutrol through a separate IV line in the contralateral arm.[59653]
 
MRI of the Breast
Administer as an intravenous bolus by power injector.
Follow with a 0.9% Sodium Chloride Injection flush to ensure complete administration of the contrast.
Start image acquisition after contrast administration and then repeat sequentially to determine peak intensity and wash-out.[59653]
 
MRI of the Central Nervous System
Administer as an intravenous injection, manually or by power injector, at a flow rate of approximately 2 mL/second.
Follow with a 0.9% Sodium Chloride Injection flush to ensure complete administration of the contrast.
Post-contrast MRI can begin immediately after contrast administration.[59653]
 
MRA
Image acquisition should coincide with peak arterial concentration, which varies among patients.
Adults: Administer by power injector, at a flow rate of approximately 1.5 mL/second. Follow with a 30 mL 0.9% Sodium Chloride Injection flush at the same rate to ensure complete administration of the contrast.
Pediatrics: Administer by power injector or manually. Follow with a 0.9% Sodium Chloride Injection flush to ensure complete administration of the contrast.[59653]

anaphylactoid reactions / Rapid / 0-0.1
nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) / Delayed / Incidence not known
renal failure (unspecified) / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
angioedema / Rapid / Incidence not known
cardiac arrest / Early / Incidence not known
respiratory arrest / Rapid / Incidence not known
bronchospasm / Rapid / Incidence not known
cyanosis / Early / Incidence not known
laryngeal edema / Rapid / Incidence not known
pulmonary edema / Early / Incidence not known

erythema / Early / 0.2-0.2
dyspnea / Early / 0.1-0.1
sinus tachycardia / Rapid / 0-0.1
palpitations / Early / 0-0.1
conjunctivitis / Delayed / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypertension / Early / Incidence not known

headache / Early / 1.7-1.7
nausea / Early / 1.2-1.2
dizziness / Early / 0.5-0.5
injection site reaction / Rapid / 0.4-0.4
dysgeusia / Early / 0.4-0.4
vomiting / Early / 0.4-0.4
maculopapular rash / Early / 0.3-0.3
rash / Early / 0.3-0.3
pruritus / Rapid / 0.2-0.2
paresthesias / Delayed / 0.2-0.2
urticaria / Rapid / 0.1-0.1
malaise / Early / 0-0.1
parosmia / Delayed / 0-0.1
xerostomia / Early / 0-0.1
cough / Delayed / Incidence not known
sneezing / Early / Incidence not known
pallor / Early / Incidence not known
hyperhidrosis / Delayed / Incidence not known

Serious adverse reactions, including nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy) (NSF/NFD), have been reported in patients with renal impairment after receiving gadolinium-based contrast agents (GBCAs), such as gadobutrol. NSF may result in fatal or debilitating systemic fibrosis affecting the internal organs, muscle, and skin. Patients at highest risk for NSF are those with chronic, severe renal disease or renal failure (glomerular filtration rate [GFR] less than 30 mL/min/1.73 m2) and patients with acute renal injury. Avoid use of GBCAs in patients with impaired drug elimination unless the diagnostic information is essential and not available with non-contrasted MRI or other modalities. Use of higher than recommended doses or repeated administration may increase the risk for NSF; therefore, administer the lowest dose necessary for adequate imaging and, if needed, only repeat the dose after a sufficient period of time has passed for elimination of the agent from the body. Gadobutrol is removed by hemodialysis. For patients receiving hemodialysis, it may be prudent to dialyze patients after receiving the contrast agents, although a relationship between dialysis and prevention of NSF has not been determined. Of note, hemodialysis is the preferred method of dialysis as continuous ambulatory peritoneal dialysis does not appear to be as effective in eliminating GBCAs. All patients should be screened for evidence of renal dysfunction by obtaining a medical history or laboratory results prior to the administration of GBCAs. Acute renal injury occurs commonly after surgery, severe infection, injury, or drug-induced renal toxicity. In patients with acute renal injury, serum creatinine concentrations and estimated GFR may not reliably assess renal function; therefore, obtaining a medical history in these patients is of utmost importance. For patients at risk of chronic renal disease (e.g., patients with hypertension, diabetes mellitus, or geriatric patients [older than 60 years of age]), estimate the GFR through laboratory testing. Counsel patients on the signs and symptoms of NSF/NFD. Report possible cases of NSF to the FDA through the FDA MedWatch program at 800-FDA-1088 and to the manufacturer at 888-842-2937. In contrast, guidelines suggest kidney function screening is optional for American College of Radiology (ACR) group II GBCAs, which includes gadobutrol, given risk of NSF is very low comparatively; the risk of NSF is very low for a standard dose (0.1 mmol/kg) of group II GBCA, even in patients with eGFR less than 30 mL/minute/1.73 m2. Do not withhold or delay group II GBCA in patients with kidney disease if harm would result from not proceeding with an indicated contrast-enhanced MRI. If multiple urgent group II GBCA doses are indicated, do not delay subsequent dose(s) for NSF concerns. If not urgent, delaying the subsequent dose(s) for more than 24 hours or performing intercurrent dialysis can promote GBCA clearance. In general, do not initiate or alter dialysis based on group II GBCA administration. These recommendations are not altered by patients receiving concomitant nephrotoxic medications, chemotherapy, or contrast-enhanced CT.

Gadavist

Rx

Parenteral, paramagnetic, gadolinium-based contrast agent
Used for MRI to assess myocardial perfusion in patients with known or suspected coronary artery disease, assess presence and extent of malignant breast disease, and detect and visualize areas with disrupted blood-brain barrier and/or abnormal vascularity within the CNS and for MRA to evaluate known or suspected supra-aortic or renal artery disease
May be associated with nephrogenic systemic fibrosis

0.1 mL/kg (0.1 mmol/kg) IV once. Imaging may begin immediately after administration. The manufacturer provides weight-based dose volumes as follows: 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.

0.1 mL/kg (0.1 mmol/kg) IV once. Imaging may begin immediately after administration. The manufacturer provides weight-based dose volumes as follows: 2.5 kg: 0.25 mL; 5 kg: 0.5 mL; 10 kg: 1 mL; 15 kg: 1.5 mL; 20 kg: 2 mL; 25 kg: 2.5 mL; 30 kg: 3 mL; 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.

0.1 mL/kg (0.1 mmol/kg) IV once. Imaging may begin after administration and then repeat sequentially to determine peak intensity and wash-out. The manufacturer provides weight-based dose volumes as follows: 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.

0.05 mL/kg (0.05 mmol/kg) IV at peak pharmacologic stress, followed by 0.05 mL/kg (0.05 mmol/kg) IV at rest. The manufacturer provides weight-based dose volumes as follows (divided into 2 separate, equal injections): 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.[59653]

0.1 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection by power injector at a rate of approximately 1.5 mL/second. Imaging should coincide with peak arterial concentration, which varies among patients. The manufacturer provides weight-based dose volumes as follow: 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.

0.1 mL/kg (0.1 mmol/kg) administered as a single IV bolus injection by power injector or manually. Imaging should coincide with peak arterial concentration, which varies among patients. The manufacturer provides weight-based dose volumes as follow: 2.5 kg: 0.25 mL; 5 kg: 0.5 mL; 10 kg: 1 mL; 15 kg: 1.5 mL; 20 kg: 2 mL; 25 kg: 2.5 mL; 30 kg: 3 mL; 35 kg: 3.5 mL; 40 kg: 4 mL; 45 kg: 4.5 mL; 50 kg: 5 mL; 60 kg: 6 mL; 70 kg: 7 mL; 80 kg: 8 mL; 90 kg: 9 mL; 100 kg: 10 mL; 110 kg: 11 mL; 120 kg: 12 mL; 130 kg: 13 mL; 140 kg: 14 mL.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

No dosage adjustments are recommended. Do not exceed the recommended dose and allow sufficient time for elimination prior to any repeat administration. Avoid use in patients with chronic, severe renal disease (GFR < 30 mL/min/1.73m2) and in patients with acute kidney injury unless the diagnostic information is essential and not available with non-contrast imaging or other modalities; these patients are at highest risk for nephrogenic systemic fibrosis.
Intermittent hemodialysis
Gadobutrol is removed from the body by hemodialysis. For patients receiving hemodialysis, consider initiating a hemodialysis session after drug administration in order to enhance clearance of the contrast agent.

Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.
Tenofovir Alafenamide: (Moderate) Monitor for changes in renal function if tenofovir alafenamide is administered in combination with nephrotoxic agents, such as radiopaque contrast agents. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with a drug that reduces renal function or competes for active tubular secretion may increase concentrations of tenofovir and other renally eliminated drugs; thus, increasing the risk of developing renal-related adverse reactions.

Gadavist/Gadobutrol Intravenous Inj Sol: 1mMole, 1mL

0.1 mL/kg (0.1 mmol/kg) IV single dose.

0.1 mL/kg (0.1 mmol/kg) IV single dose.

0.1 mL/kg (0.1 mmol/kg) IV single dose.

0.1 mL/kg (0.1 mmol/kg) IV single dose.

0.1 mL/kg (0.1 mmol/kg) IV single dose.

0.1 mL/kg (0.1 mmol/kg) IV single dose.

Gadobutrol, a paramagnetic agent, is used to enhance lesion detection and characterization during magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). In magnetic resonance, the visualization of normal and pathological tissue depends on changes in the radiofrequency signal intensity that occur with: differences in proton density; differences of the spin-lattice or longitudinal relaxation time (T1); and differences in the spin-spin or transverse relaxation time (T2). Gadobutrol causes increased signal intensity by developing a magnetic moment when placed in a magnetic field. This magnetic moment causes the T1 and T2 relaxation times to shorten in target tissues. The extent by which gadobutrol decreases the T1 and T2 relaxation times, and subsequently enhances the signal, depends on the concentration of the drug within the tissue, field strength within the magnetic resonance system, and the relative ratio of T1 and T2. When administered at the manufacturer recommended dose, effects on T1 relaxation time are observed with the greatest sensitivity in T1-weighted magnetic resonance sequences.

Gadobutrol is administered intravenously. Following administration, the drug does not bind to any particular plasma protein; it rapidly distributes into the extracellular space. Gadobutrol does not undergo metabolism. It is excreted in the urine, via glomerular filtration, as an unchanged drug. The elimination half-life is approximately 2 hours, with > 90% of the administered dose eliminated within 12 hours.
 
Affected cytochrome P450 isoenzymes: none

Use gadobutrol during pregnancy only if imaging is essential and cannot be delayed. Gadolinium-based contrast agents (GBCAs) cross the placenta and result in fetal exposure and gadolinium retention. Pregnant women may be at greater risk for gadolinium retention. Data on the association between GBCAs and adverse fetal outcomes in human pregnancy are limited and inconclusive. In animal studies, gadobutrol was not found to be teratogenic; however, at doses of 8- to 12-times the recommended human dose, gadobutrol was lethal to the embryo when administered to pregnant rats, rabbits, and monkeys. The American College of Radiology (ACR) manual on contrast media acknowledges that a standard gadolinium-based contrast agent (GBCA) crosses the primate placenta; however, the risk to the human fetus is unknown. Therefore, the ACR advises against GBCA routine use in pregnant women; GBCA should only be administered during pregnancy if absolutely necessary and only after informed consent is obtained. The Guidelines for Computed Tomography and Magnetic Resonance Imaging in Pregnancy and Lactation state that because of the potential for fetal toxicity, the drug should only be used during pregnancy if deemed absolutely essential.

There are no data on the presence of gadobutrol in human milk, the effects on the breast-fed infant, or the effects on milk production. Limited data demonstrates that breast-feeding after administration of another gadolinium-based contrast agent (GBCA) to the mother would result in the infant receiving an oral dose of 0.01% to 0.04% of the maternal dose. Gastrointestinal absorption of a GBCA is limited. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for gadobutrol and any potential adverse effects on the breast-fed infant from gadobutrol or the underlying maternal condition. Previous American Academy of Pediatrics (AAP) recommendations considered GBCAs compatible with breast-feeding. Additionally, the Guidelines for Computed Tomography and Magnetic Resonance Imaging Use During Pregnancy and Lactation and the American College of Radiology (ACR) manual on contrast media state that lactating women receiving GBCAs can continue to breast-feed without interruption. The reasoning for this recommendation is based on estimates of limited systemic exposure in the breast-fed infant and reviews that conclude maternally administered drug pose no risk to the nursing infant.