dcsimg

Gadovist® (gadobutrol) injection 1 mmol/mL

Gadovist Banner

Gadovist® (gadobutrol) injection

The Gadovist® macrocylcic chelate binds the Gd3+ ion in a cage, which imparts added strength compared with a linear structure.¹

* Relaxivity of Gadovist® is 5.2 L•mmol–1• s–1 at 1.5 Tesla (r1 in plasma at 37°C)2

High Relaxivity*, Macrocyclic Bond

Strong Signal Enhancement

Factors involved in signal enhancement

Signal enhancement is based on multiple factors, including relaxivity, magnetic field strength, and concentration in tissue.¹


What is relaxivity?

Relaxivity is a measure of the ability of magnetic compounds—like MR-contrast agents—to increase the relaxation rates of surrounding water protons. A high-relaxivity contrast agent may improve signal enhancement in contrast-enhanced images.

RELAXIVITIES OF GBCAs1
Product Name Relaxivity (r1) at 1.5 Tesla*
Gadovist (gadobutrol) injection 5.2
Primovist (gadoxetate disodium) injection 6.9
Magnevist (gadopentetate dimeglumine) injection 4.1
gadobenate dimeglumine injection 6.3
gadodiamide injection 4.3
gadoteridol injection 4.1
Dotarem® (Gadoterate meglumine) Injection 3.6

*Relaxivity of Gadovist® is 5.2 L•mmol–1• s–1 at 1.5 Tesla (r1 in plasma at 37°C)2


Macrocyclic Structure

Gadolinium-chelate complexes

The most widely used MRI-contrast agents are gadolinium-based, due to the high paramagnetism of the gadolinium ion, and are manufactured with a ligand bound to the central gadolinium (Gd3+) ion. The ligand forms a stable chelated complex around the gadolinium ion and reduces the chance of toxicity that could result from exposure to free gadolinium in the body.3


Structural classes of GBCA

There are 2 structural classes of GBCA chelates—macrocyclic and linear.4 Macrocyclic ligands bind gadolinium ions in a cage structure, while linear ligands bind gadolinium ions with a chain structure.5 Gadovist® is a macrocyclic agent approved for use in magnetic resonance imaging in Canada. Molecular structures of representative agents from each class are shown below.



Structures of GBCA approved for CNS imaging:

LINEAR MACROCYCLIC
Magnevist (gadopentetate dimeglu mine) injection Gadovist (gadobutrol) injection
gadobenate dimeglumine injection gadoteridol injection
gadodiamide injection
gadoversetamide injection

References:

  1. Gadovist® (gadobutrol injection) Product Monograph. Bayer Inc.
  2. Roher M, Bauer H, Mintorovitch J, et al. Comparison of magnetic properties of MRI contrast media solutions at different field strengths.Invest Radiol. 2005;40: 715724.
  3. Frenzel T, Lengsfeld P, Schirmer H, et al. Stability of gadolinium-based magnetic resonance imaging contrast agents in human serum at 37 degrees C. Invest Radiol. 2008;43(12):817-828.
  4. Morcos SK. Extracellular gadolinium contrast agents: Differences in stability. European Journal of Radiology. 2008;66:175-179.

  5. Back to top
    Close Menu
Efficacy in MRA Clinical Trials

Clinical experience with Gadovist® in CE-MRA was obtained in two controlled phase III clinical studies, in which comparison was made with the gold standard, intra-arterial digital subtraction angiography (DSA). A total of 383 patients were enrolled, of which 362 were evaluable for efficacy analyses.


In both studies, the clinical evaluation as well as all 3 blinded readers reached the predefined level of statistical significance for the lower limit of the 95% confidence interval for the rate of agreement of the clinically relevant diagnosis groups between CE-MRA and DSA for prospectively defined vessel segments.


Results of the Primary Efficacy Analysis in Two Clinical Studies: Body Arteries
N Agreement%
[Lower Limit 95% Cl. Upper Limit 95% Cl]*
Clinical Reader 176 96.6 [92.7, 98.7]
Blinded Reader 1 173 90.2 [84.7, 94.2]
Blinded Reader 2 171 86.6 [80.5, 91.3]
Blinded Reader 3 174 87.9 [82.1, 92.4]
Results of the Primary Efficacy Analysis in Two Clinical Studies: Peripheral Arteries
N Agreement%
[Lower Limit 95% Cl. Upper Limit 95% Cl]*
Clinical Reader 186 94.1 [89.7, 97.0]
Blinded Reader 1 178 86.0 [80.0, 90.7]
Blinded Reader 2 179 866 [80.7, 912]
Blinded Reader 3 181 87.9 [82.2. 92.2]

*Cl= confidence interval


Back to top
Close Menu
Efficacy in CNS Clinical Trials

Clinical experience with Gadovist® in brain and spine imaging including brain perfusion was obtained in a total of 6 studies. In all, 852 patients were enrolled in these studies from which 822 patients were evaluable for efficacy.


Diagnostic Accuracy1; Four studies evaluated the diagnostic accuracy of Gadovist® as primary and/or secondary parameters. A dose-related improvement for all of these parameters could be shown after administration of Gadovist® compared to the unenhanced scans in all studies performed on conventional T1-weighted imaging.

  • Additional information regarding lesion size and lesion demarcation was achieved in 46% to 97% of patients.
  • Additional detected lesions can be expected almost exclusively in patients with brain/spine metastases and multiple sclerosis. - In 47% of the patients evaluated in one study, additional lesions were detected after administration of 0.1 mmol/kg Gadovist® .

Diagnostic Confidence1: Diagnostic confidence was assessed in some studies and showed that after an initial dose of 0.1 mmol/kg Gadovist®, there was an increase in confidence by 85% to 90% relative to unenhanced scans.


Therapeutic Efficacy11: A change in management or therapy was reported after administration of 0.1 mmol/kg Gadovist® in 15.7% and 18.2% of patients in two studies, respectively. For primary brain tumors, a change in patient management or therapy was reported in 13.7 % of patients. In metastatic patients, a change was reported in 12.5% at a dose of 0.1 mmol/kg Gadovist®. The 0.3 mmol/kg Gadovist® dose led to a further change in management in 2.3% of patients with brain metastases and in 8.3% of patients with spinal tumors.


Improved assessment of normal and abnormal CNS anatomy

Serious Warnings and Precautions

NEPHROGENIC SYSTEMIC FIBROSIS

Gadolinium-based contrast agents (GBCAs) increase the risk for Nephrogenic Systemic Fibrosis (NSF) in patients with:

  • acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2), or
  • acute renal failure / acute kidney injury

In these patients, avoid use of GBCAs unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle, and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a GBCA, do not exceed the recommended dose (see DOSAGE AND ADMINISTRATION – Recommended Dose and Dosage Adjustment in the Product Monograph) and allow a sufficient period of time for elimination of the agent from the body prior to any readministration. (See WARNINGS AND PRECAUTIONS – General, Renal and Skin, and ADVERSE REACTIONS – Postmarket Adverse Drug

Reactions in the Product Monograph)1

The most common adverse events reported following administration of Gadovist® for Central Nervous System (CNS) Indications were: headache (0.9%), vasodilatation (0.6%), nausea (0.5%), injection site pain (0.4%), dizziness (0.3%), rash (0.3%), and dyspnea (0.3%). These reactions were mild to moderate in severity. The most common adverse events reported following administration of Gadovist® for MRA indications were thermal sensations (2.5%) and headache (1.1%). Pediatric Population - In children less than 2 years of age, safety is available in 44 subjects. Only one subject (2.3%) experienced a drug-related adverse event (vomiting of mild intensity). In children 2 to 17 years of age, most common adverse events were dysgeusia (1.4%) and feeling hot (1.4%).

References:
1.
Gadovist® (gadobutrol injection) Product Monograph. Bayer Inc.

Back to top
Close Menu
Pediatric – 0 years onwards

One contrast agent for every age1

Gadovist® 1.0 is approved for use in adults and children off all ages including term newborns for contrast enhancement during cranial and spinal MRI investigations, CE-MRA, contrast enhanced MRI of the breast to assess the presence and extent of malignant breast diseases, MRI of the kidney, and for perfusion studies for the diagnosis of stroke, detection of focal cerebral ischemia and tumor perfusion.


Putting safety first


The safety profile and tolerability of Gadovist® 1.0 (0.1 mmol/kg body weight) throughout all age groups has been confirmed in different studies and revealed to be applicable in a broad range of pediatric and adult pathologies.3

  •  proven safety profile and tolerability in children and adults.1-6
  •  Renally excreted in all patient populations – high clearance rates in children and adults. 3,5,7
  •  Macrocyclic compound – class with high stability. 8

Case studies: Imaging with Gadovist® 1.0 in children throughout all ages.

The following case studies show how Gadovist® 1.0 enhanced MRI can be used to aid diagnosis in pediatric patients with different disease states.


References:

  1. Bayer HealthCare Gadovist® 1.0 Product Monograph
  2. Hahn G et al.RSNA abstract No: SSM20-04,2014.
  3. Hahn G et al.Invest Radiol 2009;44(12):776–783.
  4. Staks T et al.Invest Radiol 1994;29:709–715.
  5. Balzer JO et al.Eur Rdiol 2003;13:2067–2074.
  6. Forsting M, Palkowitsch PEur J Radiol 2010;74(3):186–192.
  7. Tombach B et al.Radiol 2001;218:651–657.
  8. Frenzel T et al.Invest Radiol 2008;43:817–828.

Back to top
Close Menu
Safety in Clinical Trials

Adult Safety

In 38 clinical trials of 6,330 patients worldwide, Gadovist® established the following safety profile1, 2 Adverse reactions associated with the use of Gadovist® are usually mild to moderate in severity and transient in nature. The adverse reactions that occured in ≥0.1% of subjects who received Gadovist® were1, 2:

ADVERSE REACTIONS
Reaction Rate(%), n=6,330
Headache 1.5
Nausea 1.2
Dizziness 0.5
Dysgeusia 0.4
Feeling hot 0.4
Injection site reactions 0.4
Vomiting 0.4
Rash
(includes generalized, macular, popular prurrtic)
0.3
Pruritus (includes generalized) 0.2
Erythema 0.2
Hypersensitivity/Analphylactoid 0.1
Dyspnea 0.1
Paresthesia 0.1

Pediatrics Safety:

The pharmacokinetics and safety of GADOVIST 1.0 were evaluated in two single dose Phase I/III studies. Safety is available in 184 subjects <18 years of age. In children 2-17 years of age out of 138 subjects, a total of 8 patients (5.8%) experienced 10 adverse events considered as drug-related; those observed most often were dysgeusia in 2 subjects (1.4%) and feeling hot in 2 subjects (1.4%), and these were mild in severity. In children less than 2 years of age, safety is available in 44 subjects. Only one subject (2.3%) experienced a drug-related adverse event (vomiting of mild intensity). Adverse events were reported in 18 subjects (40.9%), the maximum intensity was mild intensity in 13 subjects (29.5%), moderate intensity in 2 subjects (4.5%), and severe intensity serious adverse events in 3 subjects (6.8%; subdural empyema, respiratory failure, and infected cyst).

Number of Pediatric Subjects with Drug-Related Treatment-Emergent Adverse Events by System Organ Class and Preferred Term1


a. Coding per MedDRA version 11.0 (study 310788) and version 16.1 (study 91741)

References:

  1. Gadovist® Product Monograph
  2. Gadavist® Prescribing Information

Back to top
Close Menu
Dosing

Double the Concentration, Half the Volume

Concentration

Gadovist® is formulated at a higher concentration (1 mmol/mL) compared to certain other gadolinium-based contrast agents, resulting in a lower volume of administration and a more compact bolus compared to 0.5 molar agents.


Dosing Information* - Easy standard dosing1

Recommended Dose: Recommended dosage with Gadovist® 1.0 depends on the indication.1

Generally, a single injection of 0.1 mL/kg body weight (0.1 mmol/kg body weight) is sufficient to answer the clinical questions.1

Administration: Administer intravenously as a bolus, manually or by power injector. For dynamic studies, the use of a power injector is recommended.

Maximum Single Dose per Injection: 0.3 mL/kg body weight may be administered at maximum.1

Special Populations

  • Pediatric Population (0-17 years of age): 
    0.1 mL/kg for all indications.1

  • Geriatric Population:
    No dose adjustments are necessary.1

  • Hepatically or Renally Impaired (use with caution in renal impairment): 
    No dose adjustments are necessary.1



Dosing Calculator

lbs Kgs
         * For complete dosing information, refer to the Gadovist® 1.0 Product Monograph, Bayer Inc.
  1. within 30 minutes of the 1st injection
  2. For perfusion studies, the use of a nonmagnetic, automatic injector is recommended at an infusion rate of 3-5 mL/sec

References:

  1. Gadovist® Product Monograph. Bayer Inc.
Back to top
Close Menu
Packing

Gadovist® is a clear, colorless-to-pale yellow solution containing 1 mmol gadobutrol per milliliter (equivalent to 604.72 mg gadobutrol per mL).


Gadovist® is supplied in the following sizes:

SINGLE-DOSE VIALS (mL) Vial Size
(mL)
PRODUCT CODE
7.5 80782447
15 3200250
30 80684836
Back to top
Close Menu

Case 1 (male, 2 months):

Desmoplastic infantile ganglioglioma1

Dr. Ravi Bhargava and Dr. Michelle Noga, Canada

History

A 2-month-old male patient with left frontal lobe tumor (Desmoplastic infantile
ganglioglioma (DIG).

MR imaging

Pre-contrast, transverse T2-weighted 1, T1-weighted 2 and post-gadobutrol T1-weighted MR images show a lobulated left cerebral hemisphere mass. Post-contrast gadobutrol
(GadovistR 1.0) image 3 shows a homogeneous enhancement of the tumor with notable enhancing extension of the tumor to the dura laterally, a distinguishing feature of DIG.

Final diagnosis

Desmoplastic infantile ganglioglioma.

Case 2 (female, 2 months):

Right parotid hemangioendothelioma1

Dr. Ravi Bhargava and Dr. Michelle Noga, Canada

History

A 2-month-old female with a proliferating right parotid hemangioma.

MR imaging

The coronal STIR T2-weighted image 1 shows a round, hyperintense mass to the right side of the neck. The transverse T2-weighted sequence 2 shows the mass is located in the right parotid gland. Transverse T2-weighted sequence 3 and MR angiogram image 4 show a high velocity vessel producing a linear flow void within the medial aspect of the mass. Pre-contrast, T1-weighted 5 and post-contrast gadobutrol (GadovistR 1.0, 6) images show marked homogeneous enhancement of the tumor.

Final diagnosis

Right parotid hemangioendothelioma.

Case 3 (male, 5 months):

Optic pathway glioma1

Dr. Ravi Bhargava and Dr. Michelle Noga, Canada

History

A 5-month-old male with an optic pathway glioma.

MR imaging

Pre-contrast, sagittal T1-weighted image 1 and T1-weighted post-contrast gadobutrol sequence (GadovistR 1.0, 2) show an enhancing suprasellar mass that has enlarged and infiltrated the optic chiasm. Posterior extension of the mass has a mass effect on the brainstem. Post-contrast gadobutrol (GadovistR 1.0), T1-weighted transverse 2 and coronal 4 images show extension of the glioma into the left optic nerve with intense homogeneous enhancement.

Final diagnosis

Optic pathway glioma with posterior extension.

Case 4 (female, 7 months):

Portal vein thrombosis with partial recanalization1

Dr. Ravi Bhargava and Dr. Michelle Noga, Canada

History

A 7-month-old female who previously underwent surgery for hepatoportoenterostomy and enteroenterostomy for biliary atresia returns with ascites and no flow in the main, left, and right portal veins on ultrasound. Patient was treated with heparin for 5 days.

MR imaging

A maximal intensity projection image from the arterial phase of axial VIBE images post-contrast gadobutrol (GadovistR 1.0, 1) shows an accessory right hepatic artery originating from the celiac axis (dashed arrow). Contrast was also demonstrated in the patent main, right, and left portal veins, indicating partial recanalization (3-4). Nodular signal loss in the walls of these veins represents residual thrombus

Final diagnosis

Portal vein thrombosis with partial recanalization.

1  Bhargava R, Noga M Magn Reson Insights 2013;6:1–12.

INDICATIONS and CLINICAL USE

GADOVIST 1.0 (gadobutrol) is a medicinal product for diagnostic use only.
GADOVIST 1.0 (gadobutrol) is indicated in adults and children of all ages including term newborns for:

  • Contrast enhancement during cranial and spinal MRI investigations and for contrast-enhanced magnetic resonance angiography (CE-MRA).
  • Contrast enhanced MRI of the breast to assess the presence and extent of malignant breast disease, and MRI of the kidney.
  • GADOVIST 1.0 is particularly suited for cases where the exclusion or demonstration of additional pathology may influence the choice of therapy or patient management, for detection of very small lesions and for visualization of tumors that do not readily take up contrast media.
  • GADOVIST 1.0 is also suited for perfusion studies for the diagnosis of stroke, detection of focal cerebral ischemia and tumor perfusion.

IMPORTANT SAFETY INFORMATION

Most Serious Warning and Precautions

NEPHROGENIC SYSTEMIC FIBROSIS

Gadolinium-based contrast agents (GBCAs) increase the risk for Nephrogenic Systemic Fibrosis (NSF) in patients with:

  • acute or chronic severe renal insufficiency (glomerular filtration rate <30 mL/min/1.73m2), or
  • acute renal failure / acute kidney injury

In these patients, avoid use of GBCAs unless the diagnostic information is essential and not available with noncontrast-enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle, and internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a GBCA, do not exceed the recommended dose (see DOSAGE AND ADMINISTRATION – Recommended Dose and Dosage Adjustment in the Product Monograph) and allow a sufficient period of time for elimination of the agent from the body prior to any readministration. (See WARNINGS AND PRECAUTIONS – General, Renal and Skin, and ADVERSE REACTIONS – Postmarket Adverse Drug Reactions in the Product Monograph)1

CONTRAINDICATIONS: Gadovist® should not be administered to patients who have experienced a life-threatening reaction to Gadovist® previously.

ADVERSE REACTIONS REPORTED FROM CLINICAL TRIALS: The most common adverse events reported following administration of Gadovist® for Central Nervous System (CNS) Indications were: headache (0.9%), vasodilatation (0.6%), nausea (0.5%), injection site pain (0.4%), dizziness (0.3%), rash (0.3%), and dyspnea (0.3%). These reactions were mild to moderate in severity. The most common adverse events reported following administration of Gadovist® for MRA indications were thermal sensations (2.5%) and headache (1.1%). Pediatric Population - Most common adverse events were dysgeusia (1.4%) and feeling hot (1.4%).

OTHER CLINICAL TRIALS: Subsequent to market introduction, additional data from clinical trials with GADOVIST 1.0 has become available. The overall safety profile of GADOVIST 1.0 is based on data from more than 6,300 patients in clinical trials. The most frequently observed adverse drug reactions (≥ 0.5 %) in patients receiving GADOVIST 1.0 are headache, nausea, and dizziness. Serious adverse drug reactions in patients receiving GADOVIST 1.0 are cardiac arrest and severe anaphylactoid reactions.

Please see Product Monograph