The Highest Relaxivity

ACR Group II Agent1-3*†

Value

 

Adding value beyond costs

CNS

 

Visualizing details

MRA

 

Diagnostic performance

Relaxivity

 

Relaxivity and signal strength

Safety

 

Safety and stability

Still the One…

Delivering Added Value in MR

The Value of Higher Relaxivity

Large-scale, well-controlled, prospective clinical studies have found minimal differences between GBCAs with similar relaxivity values.5,6

  • Improvement only in intensity of lesion enhancement but none of the other visualization endpoints when comparing Gadavist and Dotarem7
  • Significant improvements in contrast enhancement and lesion visualization were seen when comparing MultiHance with Gadavist8

MultiHance® demonstrated superiority in both qualitative and quantitative enhancement of brain lesions compared with Dotarem® at 0.1 mmol/kg dose9

Still the One…

Improving Visualization and Contrast Enhancement in CNS and MRA8-11

MultiHance demonstrated significantly improved visualization and contrast enhancement of CNS lesions when compared with Dotarem® at 0.1 mmol/kg9

View BENEFIT Study

A multicenter, double-blind, randomized, intraindividual cross-over study of 177 patients

Proven superior in both qualitative and quantitative assessments

These are representative images from reference studies; individual results may vary. 53-year-old man with left parietal glioblastoma underwent MR imaging. An aggressive-appearing mass with inhomogeneous enhancement showed greater lesion enhancement on images obtained with MultiHance.

At a standard dose…
MultiHance delivered significantly superior morphologic information and contrast enhancement of brain MR imaging compared with Dotarem.

MultiHance was preferred by readers across all endpoints (P<0.002)

  • Global diagnostic preference
  • Lesion border delineation
  • Definition of disease extent
  • Visualization of lesion internal morphology
  • Lesion contrast enhancement

No serious adverse events were reported in either group, and there were no significant differences in the incidence of adverse events (P=1.0000)

MultiHance demonstrated significantly improved visualization and contrast enhancement of CNS lesions when compared with Gadavist® at 0.1 mmol/kg8

View MERIT Study

A multicenter, double-blind, randomized, intraindividual cross-over study of 123 patients

Proven superior in both qualitative and quantitative assessments

These are representative images from reference studies; individual results may vary. 58-year-old woman with metastasis from melanoma underwent MR imaging for definite staging of metastatic disease. T1 GRE images reveal a metastasis in the right superior frontal gyrus. However, the lesion appears larger and shows more conspicuous enhancement with MultiHance compared with Gadavist.

MultiHance delivered significantly superior morphologic information and contrast enhancement of brain MR imaging compared with Gadavist.

MultiHance was preferred by readers across all endpoints (P<0.001)

  • Global diagnostic preference
  • Lesion border delineation
  • Definition of disease extent
  • Visualization of lesion internal morphology
  • Lesion contrast enhancement

MultiHance delivers high diagnostic performance in magnetic resonance angiography (MRA)10-15

View MRA Studies

Excellent vessel visualization, enhancement and stenosis detection10


These are representative images from reference studies; individual results may vary. MIP reformation (A) and volume rendered image (B) of a 3D CE MRA dataset using MultiHance show occlusion of the abdominal aorta (Leriche syndrome) just below the renal arteries (arrow in A). Note the extensive collaterals that developed due to the slow progression of the disease.


These are representative images from reference studies; individual results may vary. 52-year-old man with Leriche syndrome. Contrast-enhanced MRA with 0.1 mmol/kg MultiHance displays the occlusion of the distal abdominal aorta just above its bifurcation. The finding is confirmed by Digital Subtraction Angiography (DSA) also demonstrating the occlusion of the distal abdominal aorta.

MultiHance received excellent scores across multiple study endpoints.10

MultiHance delivered very high quality vessel visualization, great contrast enhancement, very low rate of technical failures and high-level diagnostic performance considering the full blinding to patient information of all readers10

 

The MultiHance difference: Very high vessel signal intensity in healthy volunteers16

  • MultiHance has very high signal intensity peak due to its higher relaxivity16
    • Great signal/brightness
    • High SNR may result in fast scan times and/or high resolution imaging14
  • A wide peak means that the contrast persists14,16
  • High plateau levels provide high-resolution steady-state imaging option14,16

Still the One…

The Highest Relaxivity ACR Group II Agent1-3*†

MultiHance delivers the highest relaxivity across all field strengths compared with other GBCAs2,3,17‡

Superior relaxivity for greater signal intensity

Still the One With…

Safety and Stability You Can Count On

MultiHance has been used in more than 42 million patients18

Safe for Use in patients with chronic kidney disease17

MultiHance is classified by the American College of Radiology ACR as a Group II Agent that is safe for use in:1,17

• Adults
• Pediatric patients
• Neonates with flexible dosing for patients under 2
• Patients with renal insufficiency

Safe, flexible weight-based dosing indication for CNS imaging in patients below 2 years of age17

MultiHance has no medically confirmed unconfounded reports of NSF in the literature 19-23

“Residual gadolinium has been found within the brain tissue of patients who received multiple doses of GBCAs over their lifetimes… Fortunately, there have been no reports to date to suggest these deposits are associated with histologic changes that would suggest neurotoxicity.”1

—ACR: 2021 position statement on GBCAs

MultiHance has a rapid elimination profile6,17,24,25

Mean elimination half-life in patients with severe renal impairment

Eliminated more rapidly than both Dotarem and Gadavist

MultiHance is a thermodynamically stable linear agent26,27

 

High thermodynamic stability, high conditional stability and no excess chelate26,27

MultiHance is well tolerated:17

  • The majority of observed adverse events or reactions were transient, self-limiting, and mild in intensity
  • The most commonly reported adverse events were headache (1.2%) and nausea (1.3%)

Discover a macrocyclic agent that may be appropriate for your patients

 

Explore reimbursement, savings options, and individualized resources to meet your needs

Learn more about integrating MR suites with SmartInject solutions

 

NSF=nephrogenic systemic fibrosis.
*ACR classifies Group II Agents as those with few, if any, medically confirmed unconfounded cases of NSF.
Based on relaxivity at concentrations within physiological range (3.5-5.5 g/dL)1
Based on relaxivity values for MultiHance® (gadobenate dimeglumine) injection 529 mg/mL and compared with ProHance® (Gadoteridol) Injection, 279.3 mg/mL, Gadavist® (gadobutrol), Magnevist® (gadopentetate dimeglumine) and Dotarem® (gadoterate meglumine) in plasma at 37°C at 1.5T.

References:

1. ACR committee on drugs and contrast media. ACR manual on contrast media: 2021.
2. Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H-J. Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Invest Radiol. 2005 Nov;40(11):715–724.
3. Shen Y, Goerner FL, Snyder C, et al. T1 Relaxivities of gadolinium-based magnetic resonance contrast agents in human whole blood at 1.5, 3, and 7T. Invest Radiol. 2015 May; 50(5):330-338.
4. Giesel FL, Tengg-Kobligk von H, Wilkinson ID, et al. Influence of human serum albumin on longitudinal and transverse relaxation rates (r1 and r2) of magnetic resonance contrast agents. Invest Radiol. 2006 Mar;41(3):222–228.
5. Kanal E, Maravilla K, Rowley HA. Gadolinium contrast agents for CNS imaging: current concepts and clinical evidence. AJNR Am J Neuroradiol. 2014 Dec; 35(12): 221522-26.
6. Gadavist® (gadobutrol) injection full Prescribing Information and Patient Medication Guide. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; July 2019.
7. Anzalone N, Scarabino T, Venturi C, et al. Cerebral neoplastic enhancing lesions: multicenter, randomized, crossover intraindividual comparison between gadobutrol (1.0M) and gadoterate meglumine (0.5M) at 0.1 mmol Gd/kg body weight in a clinical setting. Eur J Radiol. 2013 Jan;82:139–145.
8. Seidl Z, Vymazal J, Mechl M, et al. Does higher gadolinium concentration play a role in the morphologic assessment of brain tumors? Results of a multicenter intraindividual crossover comparison of gadobutrol versus gadobenate dimeglumine (the MERIT Study). AJNR Am J Neuroradiol. 2012 Jun-Jul;33(6):1050–1058.
9. Vaneckova M, Herman M, Smith MP, et al. The benefits of high relaxivity for brain tumor imaging: results of a multicenter intraindividual crossover comparison of gadobenate dimeglumine with gadoterate meglumine (The BENEFIT Study). AJNR Am J Neuroradiol. 2015 Sep;36(9):1589–1598.
10. Gerretsen SC, le Maire TF, Miller S, et al. Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for MR angiography of peripheral arteries. Radiology. 2010 Jun; 255(3):988-1000.
11. Schneider G, Prince MR, Meaney JFM, Ho VB, Potchen EJ. Magnetic Resonance Angiography: Techniques, Indications and Practical Applications. New York, NY: Springer; 2005.
12. Thurnher S, Miller S, Schneider G, et al. Diagnostic performance of gadobenate dimeglumine enhanced MR angiography of the iliofemoral and calf arteries: a large-scale multicenter trial. AJR AM J Roentgenol. 2007 Nov;189(5):1223-1237.
13. Wang CC, Liang HL, Hsiao CC, Chen MC, Wu TH, Wu CJ, Huang JS, Lin YH, Pan HB. Single-dose time-resolved contrast enhanced hybrid MR angiography in diagnosis of peripheral arterial disease: compared with digital subtraction angiography. J Magn Reson Imaging. 2010 Oct; 32(4): 935-942.
14. Anzidei M, Napoli A, Zaccagna F, Cavallo Marincola B, Zini C, Kirchin MA, Catalano C, Passariello R. First-pass and high-resolution steady-state magnetic resonance angiography of the peripheral arteries with gadobenate dimeglumine: an assessment of feasibility and diagnostic performance. Invest Radiol. 2011 May; 46(5): 307-316.
15. Schneider G, Pasowicz M, Vymazal J, Seidl Z, Aschauer M, Konopka M, Bilecen D, Iezzi R, Ballarati C. Gadobenate dimeglumine and gadofosveset trisodium for MR angiography of the renal arteries: Multicenter intraindividual crossover comparison. AJR Am J Roentgenol. 2010 Aug; 195(2): 476-485.
16. Knopp MV, et al. Assessment of gadobenate dimeglumine for magnetic resonance angiography phase I studies. Invest Radiol. 2002 Dec;37:706-715.
17. MultiHance (gadobenate dimeglumine) injection, 529 mg/mL full Prescribing Information. Princeton, NJ: Bracco Diagnostics Inc. 2018.
18. Data on file. Bracco Diagnostics Inc. September 2020.
19. Nandwana SB, Moreno CC, Osipow MT, Sekhar A, Cox KL. Gadobenate dimeglumine administration and Nephrogenic Systemic Fibrosis: Is there a real risk in patients with impaired renal function? Radiology. 2015 Sep;276(3):741-747.
20. Martin DR, Krishnamoorthy SK, Kalb B, Salman KN, Sharma P, Carew JD, Martin PA, Chapman AB, Ray GL, Larsen CP, Pearson TC. Decreased incidence of NSF in patients on dialysis after changing gadolinium contrast-enhanced MRI protocols. J Magn Reson Imaging. 2010 Feb;31(2):440-446.
21. Bruce R, Wentland AL, Haemel AK, Garrett RW, Sadowski DR, Djamali A, Sadowski EA. Incidence of Nephrogenic Systemic Fibrosis using gadobenate dimeglumine in 1423 patients with renal insufficiency compared with gadodiamide. Invest Radiol. 2016 Nov;51(11):701-705.
22. Abujudeh HH, Rolls H, Kaewlai R, Agarwal S, Gebreananya ZA, Saini S, Schaefer PW, Kay J. Retrospective assessment of prevalence of nephrogenic systemic fibrosis (NSF) after implementation of a new guideline for the use of gadobenate dimeglumine as a sole contrast agent for magnetic resonance examination in renally impaired patients. J Magn Reson Imaging. 2009 Dec;30(6):1335-1340.
23. Woolen SA, Shankar PR, Gagnier JJ, MacEachern MP, Singer L, Davenport MS. Risk of Nephrogenic Systemic Fibrosis in Patients With Stage 4 or 5 Chronic Kidney Disease Receiving a Group II Gadolinium-Based Contrast Agent: A Systematic Review and Meta-analysis. JAMA Intern Med. 2020 Feb; 180(2): 223-230.
24. ProHance® (Gadoteridol) injection full Prescribing Information and Patient Medication Guide. Monroe Twp., NJ:Bracco Diagnostics Inc.; December 2020.
25. Dotarem® (gadoterate meglumine) Injection full Prescribing Information and Patient Medication Guide. Princeton, NJ: Guerbet LLC.; April 2020.
26. Idée J-M, Port M, Robic C, Medina C, Sabatou M, Corot C. Role of thermodynamic and kinetic parameters in gadolinium chelate stability. J Magn Reson Imaging. 2009 Dec;30(6):1249–1258.
27. Garg A. MR Contrast Media. In: Gupta A, Chowdhury V, Khandelwal, eds. Diagnostic Radiology: Recent Advances and Applied Physics in Radiology. 2nd ed. New Delhi, India: Jaypee Brothers Medical Publishers; 2012:259-270.
MultiHance® (gadobenate dimeglumine) injection, 529 mg/mL
and
ProHance® (Gadoteridol) Injection, 279.3 mg/mL

Indications and Usage for MultiHance® (gadobenate dimeglumine) injection, 529 mg/mL:

  • Magnetic resonance imaging (MRI) of the central nervous system (CNS) in adults and pediatric patients (including term neonates) to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues
  • Magnetic resonance angiography (MRA) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease

Indications and Usage for ProHance® (Gadoteridol) Injection, 279.3 mg/mL:

CENTRAL NERVOUS SYSTEM
ProHance is indicated for use in MRI in adults and pediatric patients including term neonates to visualize lesions with disrupted blood brain barrier and/or abnormal vascularity in the brain (intracranial lesions), spine, and associated tissues.

EXTRACRANIAL/EXTRASPINAL TISSUES
ProHance is indicated for use in MRI in adults to visualize lesions in the head and neck.

IMPORTANT SAFETY INFORMATION for MultiHance and ProHance:

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS

Gadolinium-based contrast agents (GBCAs) increase the risk for 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 non-contrasted MRI or other modalities. NSF may result in fatal or debilitating systemic 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 (e.g. 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 MultiHance/ProHance dose and allow a sufficient period of time for elimination of the drug from the body prior to re-administration.

 

MultiHance (gadobenate dimeglumine) injection, 529 mg/mL

 

CONTRAINDICATIONS

MultiHance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents.

 

WARNINGS AND PRECAUTIONS

Nephrogenic Systemic Fibrosis: NSF has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeated dosing appears to increase risk.

Hypersensitivity Reactions: Anaphylactic and anaphylactoid reactions have been reported, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died. In most cases, initial symptoms occurred within minutes of MultiHance administration and resolved with prompt emergency treatment. Consider the risk for hypersensitivity reactions, especially in patients with a history of hypersensitivity reactions or a history of asthma or other allergic disorders.

Gadolinium Retention:  Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by brain, skin, kidney, liver, and spleen. At equivalent doses, retention varies among the linear agents. Retention is lowest and similar among the macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established, but they have been established in the skin and other organs in patients with impaired renal function. Minimize repetitive GBCA imaging studies, particularly closely spaced studies when possible.

Acute Renal Failure: In patients with renal insufficiency, acute renal failure requiring dialysis or worsening renal function have occurred with the use of GBCAs. The risk of renal failure may increase with increasing dose of the contrast agent. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests.

Extravasation and Injection Site Reactions: Extravasation of MultiHance may lead to injection site reactions, characterized by local pain or burning sensation, swelling, blistering, and necrosis. Exercise caution to avoid local extravasation during intravenous administration of MultiHance.

Cardiac Arrhythmias: Cardiac arrhythmias have been observed in patients receiving MultiHance in clinical trials. Assess patients for underlying conditions or medications that predispose to arrhythmias. The effects on QTc by MultiHance dose, other drugs, and medical conditions were not systematically studied.

Interference with Visualization of Certain Lesions: Certain lesions seen on non-contrast images may not be seen on contrast images. Exercise caution when interpreting contrast MR images in the absence of companion non-contrast MR images.

 

ADVERSE REACTIONS

The most commonly reported adverse reactions are nausea (1.3%) and headache (1.2%).

 

USE IN SPECIFIC POPULATIONS

Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. Use only if imaging is essential during pregnancy and cannot be delayed.

Lactation: There is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. However, limited literature reports that breastfeeding after MultiHance administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose.

Pediatric Use: MultiHance is approved for intravenous use for MRI of the CNS to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to less than 17 years of age. Adverse reactions in pediatric patients were similar to those reported in adults. No dose adjustment according to age is necessary in pediatric patients two years of age and older. For pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 mL/kg. The safety of MultiHance has not been established in preterm neonates.

 

ProHance (Gadoteridol) Injection, 279.3 mg/mL

 

CONTRAINDICATIONS

Contraindicated in patients with known allergic or hypersensitivity reactions to ProHance.

 

WARNINGS AND PRECAUTIONS

Nephrogenic Systemic Fibrosis: NSF has occurred in patients with impaired elimination of GBCAs. Higher than recommended dosing or repeated dosing appears to increase risk.

Hypersensitivity Reactions: Anaphylactic and anaphylactoid reactions have been reported, involving cardiovascular, respiratory, and/or cutaneous manifestations. Some patients experienced circulatory collapse and died. In most cases, initial symptoms occurred within minutes of administration and resolved with prompt emergency treatment. Prior to ProHance administration, ensure the availability of trained personnel and medications to treat hypersensitivity reactions. Consider these risks, especially in patients with a history of hypersensitivity reactions or a history of asthma or other allergic disorders.

Gadolinium Retention: Gadolinium is retained for months or years in several organs. The highest concentrations have been identified in the bone, followed by brain, skin, kidney, liver, and spleen. Linear GBCAs cause more retention than macrocyclic GBCAs. Consequences of gadolinium retention in the brain have not been established, but they have been established in the skin and other organs in patients with impaired renal function.

Acute Kidney Injury: In patients with chronically reduced renal function, acute kidney injury requiring dialysis has occurred with the use of GBCAs. The risk of acute kidney injury may increase with increasing dose of the contrast agent; administer the lowest dose necessary for adequate imaging.

 

ADVERSE REACTIONS

The most commonly reported adverse reactions are nausea and taste perversion with an incidence ≥ 0.9%.

 

USE IN SPECIFIC POPULATIONS

Pregnancy: GBCAs cross the human placenta and result in fetal exposure and gadolinium retention. Use only if imaging is essential during pregnancy and cannot be delayed.

Lactation: There are no data on the presence in human milk, the effects on the breastfed infant, or the effects on milk production. However, published lactation data on other GBCAs indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk.

Pediatric Use: The safety and effectiveness of ProHance have been established for use with MRI to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to 17 years of age. Adverse reactions in pediatric patients were similar to those reported in adults. No case of NSF associated with ProHance or any other GBCA has been identified in pediatric patients ages 6 years and younger.

 

Please see full Prescribing Information and Patient Medication Guide for MultiHance at here.

 

Please see full Prescribing Information and Patient Medication Guide for ProHance here.

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.

 

MultiHance is manufactured for Bracco Diagnostics Inc. by BIPSO GmbH – 78224 Singen (Germany) and by Patheon Italia S.p.A, Ferentino, Italy.

ProHance is manufactured for Bracco Diagnostics Inc. by BIPSO GmbH – 78224 Singen (Germany).

MultiHance is a registered trademark of Bracco International B.V.

ProHance is a registered trademark of Bracco Diagnostics Inc.

All other trademarks and registered trademarks are the property of their respective owners.

 

Bracco Diagnostics Inc.
259 Prospect Plains Road, Building H
Monroe Township, NJ 08831 USA
Phone: 609-514-2200
Toll Free: 1-877-272-2269 (U.S. only)
Fax: 609-514-2446

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