Version May 2024
Gadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of gadolinium-based contrast agents in these patients unless the diagnostic information is essential and not available with noncontrasted magnetic resonance imaging (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 (glomerular filtration rate [GFR] <30 mL/minute/1.73 m2) 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 (eg, >60 years, hypertension, diabetes), estimate the GFR through laboratory testing.
For patients at highest risk for NSF, do not exceed the recommended gadobutrol dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration.
Diagnostic imaging: CNS imaging and supra-aortic or renal artery angiography: Term neonates: IV: 0.1 mmol/kg (0.1 mL/kg); may begin imaging immediately after administration.
Diagnostic imaging: CNS imaging and supra-aortic or renal artery angiography: Infants, Children, and Adolescents: IV: 0.1 mmol/kg (0.1 mL/kg); may begin imaging immediately after administration.
Infants, Children, and Adolescents:
Mild to moderate kidney impairment: Dose adjustment is not recommended; however, use with caution. Risk for nephrogenic systemic fibrosis (NSF) development increases as renal function decreases.
Hemodialysis: There are no pediatric-specific recommendations; based on experience in adult patients, in patients already receiving hemodialysis, consider prompt hemodialysis following exposure. Data has shown hemodialysis enhances gadolinium elimination with average gadolinium excretory rates of 78%, 96%, and 99% in the first, second, and third hemodialysis sessions, respectively (Ref).
Peritoneal dialysis: There are no pediatric-specific recommendations, based on adult experience, peritoneal dialysis is likely less efficient at clearing gadolinium (Ref).
There are no dosage adjustments provided in the manufacturer's labeling; however, based on exclusive renal excretion of gadobutrol, dose adjustment in hepatic impairment is likely unnecessary.
(For additional information see "Gadobutrol: Drug information")
Diagnostic imaging: IV:
US labeling:
Breast malignancy imaging, CNS imaging, and supra-aortic or renal artery angiography: 0.1 mmol/kg (0.1 mL/kg); may begin imaging immediately after administration
Cardiac imaging: 0.05 mmol/kg (0.05 mL/kg) at peak pharmacological stress, followed by 0.05 mmol/kg (0.05 mL/kg) at rest
Canadian labeling:
Breast malignancy imaging: Usual dose: 0.1 mmol/kg (0.1 mL/kg); maximum: 0.3 mmol/kg (0.3 mL/kg)
CNS imaging:
General imaging: 0.1 mmol/kg (0.1 mL/kg); if needed, a second dose of 0.1 to 0.2 mmol/kg (0.1 to 0.2 mL/kg) may be repeated once within 30 minutes of the first dose
Exclusion of metastatic or recurrent tumors: 0.3 mmol/kg (0.3 mL/kg)
Perfusion studies: 0.1 to 0.3 mmol/kg (0.1 to 0.3 mL/kg)
CE-MRA:
Imaging of a single field of view (FOV):
Patient weight <75 kg: 7.5 mL
Patient weight ≥75 kg: 10 mL
Imaging >1 FOV:
Patient weight <75 kg: 15 mL
Patient weight ≥75 kg: 20 mL
Renal imaging: Usual dose: 0.1 mmol/kg (0.1 mL/kg); maximum: 0.3 mmol/kg (0.3 mL/kg)
Dose adjustment is not recommended; however, use with caution. Risk for NSF development increases as renal function decreases.
Hemodialysis: If administered to patients already receiving hemodialysis, consider prompt hemodialysis following exposure. Data has shown hemodialysis enhances gadolinium elimination with average gadolinium excretory rates of 78%, 96%, and 99% in the first, second, and third hemodialysis sessions, respectively (Ref).
Peritoneal dialysis: Likely to be less efficient at clearing gadolinium (Ref).
There are no dosage adjustments provided in the manufacturer’s labeling; however, based on exclusive renal excretion of gadobutrol, dose adjustment in hepatic impairment is likely unnecessary.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults and pediatrics.
1% to 10%:
Gastrointestinal: Nausea (1%)
Nervous system: Headache (2%)
<1%:
Cardiovascular: Palpitations, tachycardia
Dermatologic: Erythema of skin, maculopapular rash, pruritus, skin rash, urticaria
Gastrointestinal: Dysgeusia, vomiting, xerostomia
Hypersensitivity: Hypersensitivity reaction (including anaphylaxis, anaphylactic shock, angioedema)
Local: Injection-site reaction
Nervous system: Altered sense of smell, dizziness, feeling hot, loss of consciousness, malaise, paresthesia, seizure, sensation of cold
Respiratory: Dyspnea
Postmarketing:
Dermatologic: Acute generalized exanthematous pustulosis (Bordel Gómez 2018)
Renal: Nephrogenic systemic fibrosis (Wollanka 2009)
Respiratory: Acute respiratory distress syndrome (Park 2015)
Severe hypersensitivity reactions to gadobutrol or any component of the formulation.
Concerns related to adverse effects:
• Extravasation: May be a vesicant (higher osmolar contrast agents and/or higher volumes are associated with a higher risk). Ensure proper needle or catheter placement prior to and during administration. Monitor infusion site. Avoid extravasation; local tissue irritation may occur.
• Gadolinium retention: Gadolinium is retained for months or years in brain, bone, skin, and other organs (kidney, liver, spleen); the highest concentration and longest duration have been found in the bone. Linear GBCAs (gadodiamide and gadoversetamide > gadoxetate disodium, gadopentetate dimeglumine, and gadobenate dimeglumine) result in more retention than macrocyclic GBCAs (gadoterate meglumine, gadobutrol, and gadoteridol). Pathologic and clinical consequences of gadolinium retention in skin and other organs have been established in patients with impaired renal function; there also have been rare reports of pathologic skin changes in patients with normal renal function. Consequences of gadolinium retention in the brain or in patients with normal renal function have not been established. Patients with normal renal function that may be at higher risk for gadolinium retention include: patients requiring multiple lifetime doses, pregnant and pediatric patients, and patients with inflammatory conditions; take GBCA retention characteristics into consideration for these patients. Minimize repetitive GBCA imaging studies.
• Hypersensitivity: Anaphylactic and other hypersensitivity reactions (some fatal) have occurred (with mild to severe cardiovascular, respiratory or dermatologic involvement). Reactions typically occur within 30 minutes of administration; however, delayed reactions may also occur (up to several days following administration). Appropriate equipment (eg, ventilator) and emergency medications (eg, epinephrine) should be available during use. Use with caution in patients with a history of allergic reactions and/or bronchial asthma may be at an increased risk for developing hypersensitivity reactions.
• Nephrogenic systemic fibrosis (NSF): [US Boxed Warning]: Gadolinium-based contrast agent (GBCA) exposure increases the risk for NSF in patients with renal impairment; avoid use unless GBCA-enhanced imaging is essential for diagnostic purposes. The risk is highest in patients with acute kidney injury or chronic, severe renal disease (GFR <30 mL/minute/1.73 m2). The risk for NSF appears lower in patients with moderate, chronic renal disease (GFR 30 to 59 mL/minute/1.73 m2), and little, if any, in patients with mild, chronic renal disease (GFR 60 to 89 mL/minute/1.73 m2). In patients receiving hemodialysis, consider prompt initiation of hemodialysis following administration. If NSF occurs, report to manufacturer or the Food and Drug Administration (FDA).
All patients should be screened for renal dysfunction prior to administration; estimate GFR in patients at risk for chronic renal disease (diabetes, chronic hypertension, age >60 years). In patients at risk of NSF, do not exceed the recommended dosage and allow sufficient time (ie, several half-lives) for elimination prior to readministration (avoidance of readministration preferred). In patients receiving hemodialysis, consider prompt initiation of hemodialysis following administration.
Disease-related concerns:
• Renal impairment: Use with caution in patients with renal impairment. Dose-dependent worsening of renal function or acute renal failure has occurred in patients with renal insufficiency following use of gadolinium agents, generally within 48 hours following administration. In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred. Evaluate renal function in patients with renal impairment prior to use; consider follow-up monitoring.
• Seizure disorder: Use with caution in patients with a history of seizure disorder; may lower seizure threshold. Injectable antiseizure agents should be readily available.
Other warnings/precautions:
• Scan interpretation: Certain lesions may not appear with contrast-enhanced scan that do appear with noncontrast imaging; use caution when interpreting. Overestimation of extent of malignant disease in MRI of the breast has occurred in up to 50% of patients. A negative MRA study alone should not be used to rule out significant stenosis; performance of MRA for detecting arterial segments with significant stenosis (>50% renal, >70% supra-aortic) has not been shown to exceed 55%.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
Gadavist: 1 mmol/mL (2 mL, 7.5 mL, 10 mL, 15 mL, 30 mL, 65 mL)
Generic: 1 mmol/mL (2 mL, 7.5 mL, 10 mL, 15 mL, 30 mL, 65 mL)
Solution Prefilled Syringe, Intravenous [preservative free]:
Gadavist: 7.5 mmol/7.5 mL (7.5 mL); 10 mmol/10 mL (10 mL); 15 mmol/15 mL (15 mL)
May be product dependent
Solution (Gadavist Intravenous)
1 mmol/mL (per mL): $9.96
Solution (Gadobutrol Intravenous)
1 mmol/mL (per mL): $6.97
Solution Prefilled Syringe (Gadavist Intravenous)
7.5MMOL/7.5ML (per mL): $10.76
10 mmol/10 mL (per mL): $10.68
15 mmol/15 mL (per mL): $10.52
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Gadovist: 1 mmol/mL (15 mL)
Contrast agents are generally classified as high-osmolar (≥1400 mOsm/kg), low-osmolar (780 to 800 mOsm/kg), or iso-osmolar (~300 mOsm/kg) relative to plasma osmolarity (~285 mOsmol/kg).
IV: Do not administer other medications in the same IV line simultaneously.
Central nervous system imaging: Administer as an IV injection, manually or by power injector, at a rate of ~2 mL/second, followed by a NS flush. Post contrast MRI can commence immediately following contrast administration.
Supra-aortic or renal artery angiography: Administer manually or by power injector, followed by a NS flush. Image acquisition should coincide with peak arterial concentration, which varies among patients.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; initiate hyaluronidase antidote (see Management of Drug Extravasations for more details); elevate extremity.
IV: Do not administer other medications in the same IV line simultaneously.
Breast malignancy imaging: Administer as an IV bolus by power injector, followed by NS flush. Post contrast MRI can commence immediately following contrast administration.
Cardiac imaging: Administer as 2 separate IV bolus injections by power injector, at a rate of ~4 mL/second; follow each injection by a 20 mL NS flush at the same rate. If concomitantly administering a continuous infusion of pharmacologic stress agent, administer gadobutrol through a separate IV line in the contralateral arm.
CNS imaging: Administer as an IV injection, manually or by power injector, at a rate of ~2 mL/second, followed by a NS flush. Post contrast MRI can commence immediately following contrast administration.
Supra-aortic or renal artery angiography: Administer by power injector, at a rate of ~1.5 mL/second, followed by a 30 mL NS flush at the same rate. Image acquisition should coincide with peak arterial concentration, which varies among patients.
Canadian labeling: For perfusion studies, automatic injector is recommended at an infusion rate of 3 to 5 mL/second
May be a vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect; remove needle/cannula; elevate extremity. Aspiration of extravasated contrast media is not recommended (Ref). Information conflicts regarding the use of hyaluronidase; the American College of Radiology (ACR) Manual on Contrast Media does not recommend hyaluronidase in the management of contrast media extravasation (Ref); other sources suggest its utility in extravasation management for inoperable cases with compartment syndrome (Ref).
If using hyaluronidase: Intradermal or SUBQ: Dose varies based on the size of infiltration; inject a total of 5 to 250 units (~100 mL contrast reabsorbed per 15 units of hyaluronidase) around the site of extravasation (Ref).
Store at 25°C (77°F); excursions are permitted between 15°C and 30°C (59°F and 86°F). If freezing occurs; bring to room temperature before use; do not use unless solution is clear, colorless to pale yellow. Discard any unused drug. Pharmacy bulk package must be discarded within 24 hours after opening in a sterile environment.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication;
Gadavist: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/201277s020lbl.pdf#page=42
MRI to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the CNS (FDA approved in all ages); MRI to evaluate known or suspected supra-aortic or renal artery disease (FDA approved in all ages); contrast medium for use with MRI to assess the presence and extent of malignant breast disease (FDA approved in adults); cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement with known or suspected coronary artery disease (FDA approved in adults).
Gadavist may be confused with Magnevist
Gadovist [Canada and multiple international markets] may be confused with Vasovist brand name for gadofosveset [Hungary, Turkey]
None known.
There are no known significant interactions.
Gadolinium-based contrast agents may cross the placenta (ACOG 723 2017; ACR 2021).
Pregnant patients may be at increased risk for gadolinium retention. Use of gadolinium-based contrast agents in pregnancy is controversial and should be limited. A gadolinium-based contrast agent with MRI may be considered for use in pregnancy if it will significantly improve diagnostic performance and is expected to improve fetal or maternal outcome (ACOG 723 2017). In addition, use should only be considered if information needed from the MRI study cannot be acquired without using a contrast agent and cannot be deferred until after delivery. Agents with a low risk for development of nephrogenic systemic fibrosis should be used at the lowest effective dose (ACR 2021).
Renal function; signs of hypersensitivity (during and for several hours after procedure); short- and long-term monitoring of signs and symptoms of nephrogenic systemic fibrosis/nephrogenic fibrosing dermopathy (eg, burning, itching, swelling, hardening and/or tightening of skin, joint stiffness, deep hip or rib bone pain, muscle weakness, limited range of motion, and/or yellowed/raised spots on whites of eye); monitor for signs/symptoms of extravasation.
Gadobutrol is a gadolinium-containing, nonionic paramagnetic agent. Exposure to an external magnetic field induces a large local magnetic field in exposed tissues. This local magnetism disrupts water protons in the vicinity, resulting in a change in proton density and spin characteristics, which can be detected by the imaging device.
Distribution: Rapid into extracellular space
Metabolism: Not metabolized
Half-life elimination: Normal renal function: ~1.5 to 2 hours; severe renal dysfunction (CrCl <30 mL/minute): 17.6 hours (mean)
Excretion: Urine (>90% as unchanged drug); feces (negligible)
Altered kidney function: The elimination half-life was 5.8 hours in mild-to-moderately impaired patients (CrCl 30 to 80 mL/minute) and 17.6 hours in severely impaired patients not on dialysis (CrCl <30 mL/minute). The mean AUC in patients with healthy renal function was 1.1 mmol•h/L compared with 4 mmol•h/L in patients with mild-to-moderate renal impairment, and 11.5 mmol•h/L in patients with severe renal impairment.
Older adult: AUC was slightly higher and clearance slightly lower in elderly patients.
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