Seeing is Believing...Look Beneath the Surface

For more medical information, call Bracco Professional Services: 1-800-257-5181 Option 2

For more information about ProHance, visit www.prohance.com

For more information about Bracco Products, visit www.bracco.com or call Bracco Customer Service 1-877-BRACCO-9 (1-877-272-2269)

References

1. Idee JM, Port C, Raynal I, et al. Clinical and geological consequences of transmetallation induced by contrast agents for magnetic resonance imaging: a review. Fundamental and Clinical Pharmacology. 2006; 20:563-576.

2. Prince M., et al. “Gadodiamide Administration Causes Spurious Hypocalcemia” Radiol. 2003; 227, 3: 639-646. 3. Tweedle MF, Wedeking P, Kumar K. Biodistribution of Radiolabeled, Formulated Gadopentetate, Gadoteridol, Gadoterate, and Gadodiamide in Mice and

Rats. Invest Radiol. 1995; 30; 372-380.4. Gibby WA, Gibby KA, Gibby WA. Comparison of Gd DTPA-BMA (Omniscan) versus Gd HP-D03A (ProHance) Retention in Human Bone Tissue by

Inductively Coupled Plasma Atomic Emission Spectroscopy. Invest Radiol. 2004; 39: 138-142.5. Kirchin M, Runge V, Contrast Agents for Magnetic Resonance Imaging Safety Update. Top Magn Reson Imaging. 2003;14:56. ProHance® (gadoteridol) injection 279.3 mg/mL full Prescribing Information. Princeton, NJ: Bracco Diagnostics Inc.; May 2007. 7. Omniscan™ (gadodiamide) injection, full Prescribing Information. Princeton, NJ: GE HealthCare Inc.; June 2007. 8. OptiMARK® (gadoversetamide injection) full Prescribing Information. St. Louis, MO: Mallinckrodt Inc.; May 2007 9. Magnevist® (brand of gadopentetate dimeglumine) injection full Prescribing Information. Wayne, NJ: Bayer Healthcare Pharmaceuticals Inc.; June 2007 10. MultiHance® (gadobenate dimeglumine) injection 529 mg/mL full Prescribing Information. Princeton, NJ: Bracco Diagnostics Inc.; May 2007. 11. Emerson J. et al. “Spurious Hypocalcemia after Omniscan- or OptiMARK-Enhanced Magnetic Resonance Imaging.” Arch Pathol Lab Med. 2004; Vol 128:

1151-1156.

ProHance is a registered trademark of Bracco Diagnostics Inc.MultiHance is a registered trademark of Bracco Diagnostics Inc. Magnevist is registered trademark of Bayer HealthCare Phamaceuticals Inc. Omniscan is a trademark of GE Healthcare Inc.OptiMARK is a registered trademark of Covidien.

© BDI 2008

08-020108

Of the gadolinium-based contrast agents available for use in the U.S.:

~ ProHance is the first and only macrocyclic and nonionic agent.

~ ProHance has the highest thermodynamic stability constant, conditional stability and lowest osmolality of the nonionic agents1 (Refer to chart on page 4).

~ ProHance is the only nonionic MRI agent that does not interfere with colorimetric serum calcium determinations.2

Seeing is Believing...Look Beneath the Surface

WARNING: NEPHROGENIC SYSTEMIC FIBROSISGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with:· acute or chronic severe renal insufficiency (glomerular filtration rate <30mL/min/1.73m2), or· acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time of elimination of the agent from the body prior to any readministration.

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Please consult full Prescribing Information including the boxed WARNING in the pocket of this brochure.

4 5

Observe the stability of ProHance

ProHance, with its macrocyclic molecular structure, has the highest thermodynamic stability constant and conditional stability of the nonionic gadolinium-based MR contrast agents available in the U.S.1,3,4,5

ProHance®

(gadoteridol)6

Omniscan™ (gadodiamide)7

OptiMARK® (gadoversetamide)8

Magnevist® (gadopentetate dimeglumine)9

MultiHance®

(gadobenate dimeglumine)10

Molecular Structure Macrocyclic Linear Linear Linear Linear

Ionicity Nonionic Nonionic Nonionic Ionic Ionic

Osmolality (mOsm/kg, 37ºC) 630 789 1110 1960 1970Viscosity (cP, 37ºC) 1.3 1.4 2.0 2.9 5.3

Maximum Adult Dose (mmol/kg) 0.3 0.3 0.1 0.1 0.1

Thermodynamic Stability Constant (pH=1.0)

23.8 16.9 16.6 22.1 22.6

Conditional Stability (pH=7.4)

17.1 14.9 15.0 17.9 18.4

Dissociation half-life (@25°C in 0.1 N HCI)

3 h 35 sec Not Available 10 min Not Available

Amount of excess chelate

0.23 12 28.4 0.4 0

The Only Nonionic Contrast Agent That Does Not Interfere with Serum Calcium Determinations by Colorimetric Methods2,11

~ In one clinical study with ProHance and Omniscan, false hypocalcemia was noted in 15.7% of 1049 examinations performed with Omniscan.2

~ In the same study, 25 examinations (2.4%), the decreases in serum calcium readings resulted in measurements of “critical” hypocalcemia, resulting in inappropriate and potentially dangerous calcium therapy in 18 patients.2

0

2

4

6

8

9

7

5

3

1

2 4 531

(Gd)mM

Ser

um C

alci

um m

g/d

L

OptiMark®

Omniscan®

ProHance®Saline

Gadopentatedimegiumine

Gadoteridol (ProHance®)

Gadovesetamide(OptiMARK®)

Gadodiamide(Omniscan®)

Magnevist®

Chart taken from Prince M., et al. “Gadodiamide Administration Causes Spurious Hypocalcemia” Radiology 2003; 227, 3: 639-646

*Magnevist is an ionic agent

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Please consult full Prescribing Information including the boxed WARNING in the pocket of this brochure.

WARNING: NEPHROGENIC SYSTEMIC FIBROSISGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with:· acute or chronic severe renal insufficiency (glomerular filtration rate <30mL/min/1.73m2), or· acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time of elimination of the agent from the body prior to any readministration.

6 7

Observe the qualities of ProHance

Standard Dose

A B C

A) T1-weighted precontrast image shows a rounded mass in the jugular foramen region.

B) T2-weighted image shows the same mass.

C) T1-weighted image after 0.1 mmol/kg ProHance® administration shows bright heterogeneous enhancement of the tumor, characteristic of Schwannoma.

Courtesy of Zoarsky GH, Center for the Health Sciences, UCLA

ProHance is indicated for use in MRI in adults:

~ to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues.6

~ to visualize lesions in the head and neck.6

See how ProHance helps you do more

ProHance is the only macrocyclic gadolinium-based contrast agent approved for pediatric use in the U.S.6

ProHance is indicated for use in MRI in children over 2 years of age to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues.6

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Please consult full Prescribing Information including the boxed WARNING in the pocket of this brochure.

WARNING: NEPHROGENIC SYSTEMIC FIBROSISGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with:· acute or chronic severe renal insufficiency (glomerular filtration rate <30mL/min/1.73m2), or· acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time of elimination of the agent from the body prior to any readministration.

8 9

ProHance packaging options

ProHance is available in 5, 10, 15, 20mL single-dose vials, and 50mL Multipack®* (Pharmacy Bulk Packages). Additionally, ProHance is available in prefilled syringes in 10mL and 17mL fill sizes.

ProHance® Ordering Information

1 800-631-5244

Five 5mL vials 0270-1111-04

Five 10mL vials 0270-1111-01

Five 15mL vials 0270-1111-02

Five 20mL vials 0270-1111-03

Five 10mL prefilled syringes 0270-1111-16

Five 17mL prefilled syringes 0270-1111-45

50mL Multipack* 0270-1111-70

* Not for Direct Infusion* Not for Direct Infusion

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Please consult full Prescribing Information including the boxed WARNING in the pocket of this brochure.

WARNING: NEPHROGENIC SYSTEMIC FIBROSISGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with:· acute or chronic severe renal insufficiency (glomerular filtration rate <30mL/min/1.73m2), or· acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time of elimination of the agent from the body prior to any readministration.

10

~ High chelate stability reduces interference with calcium testing.2,11

~ Indicated for use in CNS MRI for adults and pediatric patients as young as 2 years old.6

~ Flexible packaging options

~ The clinical experience of ProHance exceeds 10 million doses safely administered worldwide.

Why ProHance?

As with all paramagnetic agents, caution should be exercised in patients with deoxygenated sickle erythrocytes and renal insufficiency with or without hepatic impairment. The possibility of a reaction, including serious, life threatening, or fatal, anaphylactic or cardiovascular reactions, or other idiosyncratic reactions, should always be considered, especially in those patients with a history of a known clinical hypersensitivity or a history of asthma or other allergic respiratory disorders.

Please consult full Prescribing Information including the boxed WARNING in the pocket of this brochure.

WARNING: NEPHROGENIC SYSTEMIC FIBROSISGadolinium-based contrast agents increase the risk for nephrogenic systemic fibrosis (NSF) in patients with:· acute or chronic severe renal insufficiency (glomerular filtration rate <30mL/min/1.73m2), or· acute renal insufficiency of any severity due to the hepato-renal syndrome or in the perioperative liver transplantation period. In these patients, avoid the use of gadolinium-based contrast agents unless the diagnostic information is essential and not available with non-contrast enhanced magnetic resonance imaging (MRI). NSF may result in fatal or debilitating systemic fibrosis affecting the skin, muscle or internal organs. Screen all patients for renal dysfunction by obtaining a history and/or laboratory tests. When administering a gadolinium-based contrast agent, do not exceed the recommended dose and allow a sufficient period of time of elimination of the agent from the body prior to any readministration.