Version May 2024
Gadolinium-based contrast agents (GBCAs) increase the risk for nephrogenic systemic fibrosis (NSF) among patients with impaired elimination of the drugs. Avoid use of GBCAs in these patients unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI) or other modalities. NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle, and internal organs. The risk of 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 of NSF, do not exceed the recommended dose and allow a sufficient period of time for elimination of the drug from the body prior to any readministration.
CNS imaging: IV: 0.1 mmol/kg (0.2 mL/kg).
Renal and aorto-ilio-femoral vasculature imaging: IV: 0.1 mmol/kg (0.2 mL/kg); calculate scan delay with test bolus (1 to 2 mL) or with automatic detection technique.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; 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 (eg, within 3 hours) (Kuo 2007). 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 (Kuo 2007; Okada 2001).
Peritoneal dialysis: Likely to be less efficient at clearing gadolinium (Joffe 1998; Kuo 2007). If unable to perform hemodialysis after the procedure, more frequent peritoneal dialysis cycles are suggested (Murashima 2008).
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
(For additional information see "Gadobenate dimeglumine: Pediatric drug information")
Note: Dosing presented in mL/kg and mmol/kg; use caution.
CNS magnetic resonance imaging:
Infants and Children <2 years of age: IV: 0.1 to 0.2 mL/kg (0.05 to 0.1 mmol/kg); may begin imaging immediately after administration.
Children ≥2 years and Adolescents: IV: 0.2 mL/kg (0.1 mmol/kg); may begin imaging immediately after administration.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; acute kidney injury requiring dialysis has been reported with contrast agent use in patients with chronic renal dysfunction; risk may be increased with higher doses of contrast agent; use with caution. Risk for nephrogenic systemic fibrosis (NSF) development increases as renal function decreases.
Dialysis: There are no pediatric-specific recommendations; based on experience in adult patients, the following has been observed:
Hemodialysis: If administered to patients already receiving hemodialysis, consider prompt hemodialysis following exposure (eg, within 3 hours) (Kuo 2007). 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 (Kuo 2007; Okada 2001).
Peritoneal dialysis: Likely to be less efficient at clearing gadolinium (Joffe 1998; Kuo 2007). If unable to perform hemodialysis after the procedure, more frequent peritoneal dialysis cycles are suggested (Murashima 2008).
There are no dosage adjustments provided in the manufacturer's labeling. In adults with hepatic impairment (Child Pugh class B or C), pharmacokinetics were not significantly altered.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Feeling hot (1%), headache (1%)
Gastrointestinal: Nausea (1%), vomiting (≤1%)
Local: Injection site reaction (1%)
<1%, postmarketing, and/or case reports: Abdominal pain, altered sense of smell, anaphylactic shock, anaphylaxis, asthenia, basophilia, chest pain, chills, diarrhea, dizziness, dysgeusia, dyspnea, ECG abnormality (including PR, QRS, QT, and ST-T segment changes), eye pruritus, facial edema, fatigue, fever, first degree atrioventricular block, hyperhidrosis, hypersensitivity reaction, laboratory test abnormality (including blood chemistry, hematology, hepatic enzymes, urinalysis), laryngospasm, loss of consciousness, malaise, myalgia, nasal congestion, necrotizing pancreatitis (acute), ocular hyperemia, oral paresthesia, pain, paresthesia, pruritus, pulmonary edema, seizure, shock, skin changes (plaques), skin rash, sneezing, swelling of lips, tongue edema, tremor, urticaria, visual disturbance, wheezing, xerostomia
Hypersensitivity to gadobenate dimeglumine, any gadolinium-based contrast agent, or any component of the formulation
Concerns related to adverse effects:
• Arrhythmias: Cardiac arrhythmias have been observed; use with caution in patients with predisposing proarrhythmic conditions or concurrent proarrhythmic drug therapy. Although average changes in QTc compared to placebo were minimal (<5 msec) and no patients experienced malignant arrhythmias, numerically more patients experienced QTc prolongation between 30-60 msecs and ≥61 msecs compared to placebo in one clinical trial.
• Extravasation: Vesicant; ensure proper needle or catheter placement prior to and during administration. Monitor infusion site. Avoid extravasation. May cause injection site reactions (local burning/pain, swelling, blistering, and necrosis).
• 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 anaphylactoid reactions (some fatal) have occurred (with cardiovascular, respiratory or dermatologic involvement); symptoms typically occurred within minutes of administration. Monitor patients closely during and for up to 2 hours after infusion. If hypersensitivity occurs, begin immediate management. Appropriate equipment (eg, ventilator) and emergency medications (eg, epinephrine) should be available during use. Delayed reactions may also occur (within several hours of administration). Patients with a history of allergic reactions and/or bronchial asthma may be at an increased risk for developing hypersensitivity reactions; use caution in these patients.
• Nephrogenic systemic fibrosis: [US Boxed Warning]: Gadolinium-based contrast agents (GBCAs) exposure increases the risk for nephrogenic systemic fibrosis (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 (glomerular filtration rate [GFR] <30 mL/minute/1.73 m2). NSF may result in debilitating or fatal systemic fibrosis; affects the skin, muscle, and internal organs. Prior to administration, screen all patients for acute kidney injury or other conditions which may reduce renal function; estimate GFR in patients at risk for chronic declines in renal function (eg, age >60, chronic hypertension, diabetes). Do not exceed the recommended dose and allow a sufficient interval between readministration in patients at risk for NSF. 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).
Disease-related concerns:
• Metabolic disorders: May prolong systemic exposure with some drugs (eg, cisplatin, anthracyclines) due to competition for certain multispecific organic anion transporters (MOAT) especially in patients with decreased MOAT activity (eg, Dubin Johnson syndrome).
• 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 other gadolinium agents, generally within 48 hours following administration. Evaluate renal function in patients with renal impairment prior to use; consider follow-up monitoring.
Other warnings/precautions:
• Scan interpretation: Certain lesions may not appear with contrast-enhanced scan that do appear with noncontrast imaging; use caution when interpreting.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous [preservative free]:
MultiHance: 529 mg/mL (5 mL, 10 mL, 15 mL, 20 mL, 50 mL, 100 mL)
No
Solution (MultiHance Intravenous)
529 mg/mL (per mL): $6.81
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
MultiHance: 529 mg/mL (5 mL, 10 mL, 15 mL, 20 mL, 50 mL)
IV: Administer as rapid IV bolus injection. To ensure complete injection of medium, flush line with NS after administration using at least 5 mL (for CNS imaging) or at least 20 mL (for renal or aorto-ilio-femoral vasculature imaging). Do not administer other medications in the same IV line. May begin imaging immediately after administration.
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 (ACR 2023). 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 (ACR 2023); other sources suggest its utility in extravasation management for inoperable cases with compartment syndrome (Stefanos 2023).
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 (Stefanos 2023).
IV: Administer as rapid IV bolus injection. To ensure complete injection of contrast medium, flush line with NS after administration, using at least 5 mL (for CNS imaging) or at least 20 mL (for renal or aorto-ilio-femoral vasculature angiography). Do not administer other medications in the same IV line.
Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect; remove needle/cannula; elevate extremity. Aspiration of extravasated contrast media is not recommended (ACR 2018). 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 (ACR 2018); other sources suggest its utility in extravasation management (Bellin 2002; Reynolds 2014) (see Management of Drug Extravasations for more details).
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication;
MultiHance: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/021357s014,021358s013lbl.pdf#page=34
CNS imaging: Magnetic resonance imaging (MRI) agent to visualize CNS lesions in adults and pediatric patients with abnormal blood brain barrier or abnormal vascularity in the brain, spine, and associated tissues
Renal and aorto-ilio-femoral vasculature imaging: Magnetic resonance angiography (MRA) agent to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Chloroquine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Chloroquine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Clofazimine: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Clofazimine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Dabrafenib: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Fluorouracil Products: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Fluorouracil Products. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Haloperidol: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Ondansetron: QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Ondansetron. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pentamidine (Systemic): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of Pentamidine (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Consider alternatives to this combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Antipsychotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Class IC Antiarrhythmics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of Gadobenate Dimeglumine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): QT-prolonging Miscellaneous Agents (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Quinolone Antibiotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Gadolinium-based contrast agents may cross the placenta (ACOG 723 2017; ACR 2018).
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 2018).
Gadolinium-based contrast agents may be present in breast milk (ACOG 723 2017; ACR 2018).
Because of the low expected excretion into breast milk and the low absorption from an infant's GI tract, breastfeeding may be continued without interruption after use (ACOG 723 2017; ACR 2018). Theoretically, the taste of milk could be altered if it contains contrast media. Women who prefer to temporarily withhold breastfeeding may express and discard milk from both breasts during a period of 12 to 24 hours after the administration of contrast media. They can pump and store milk prior to the procedure then bottle feed using the stored milk during this time (ACR 2018). According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Signs of hypersensitivity (during and for several hours after procedure); renal function (prior to administration); short- and long-term monitoring of signs and symptoms of NSF (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 infusion site.
Gadobenate dimeglumine is a gadolinium-containing 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: Distributes mainly to extracellular space
Vd (central compartment):
Children 2 to 5 years: 0.2 ± 0.05 L/kg (Pirovano 2015)
Adults: 0.074 ± 0.017 to 0.158 ± 0.038 L/kg (Spinazzi 1999)
Vd (steady state): Children 2 to 5 years: 0.32 ± 0.04 L/kg (Pirovano 2015)
Vd (by area): Adults: 0.17 ± 0.016 to 0.262 ± 0.34 L/kg (Spinazzi 1999)
Metabolism: Gadobenate and dimeglumine dissociate after injection; pharmacokinetics are based on gadobenate; there is no additional biotransformation of gadobenate
Half-life elimination:
Distribution half-life:
Children 2 to 5 years: 0.13 ± 0.08 hours (Pirovano 2015)
Adults: 0.084 ± 0.012 to 0.605 ± 0.072 hours (Spinazzi 1999)
Elimination half-life:
Normal renal function:
Children 2 to 5 years: 1.22 ± 0.24 hours (Pirovano 2015)
Adults: 1.2 ± 0.09 to 1.96 ± 0.16 hours (Spinazzi 1999)
CrCl 30 to <60 mL/minute: 6.1 ± 3 hours
CrCl 10 to <30 mL/minute: 9.5 ± 3.1 hours
End-stage renal disease (ESRD) (without dialysis): 42.4 ± 24.4 hours
Excretion: Urine (78% to 96%); feces (0.6% to 4%)
Altered kidney function: In patients with end-stage renal disease requiring hemodialysis, approximately 72% of the dose was recovered by hemodialysis over a 4-hour period.
Older adult: Clearance appeared to decrease slightly with increasing age.
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