PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL – 15 mmol/15 mL – Vial Label

Dose: 0.1 mL/kg 15 mL

NDC 65219-281-05** Rx only**
Gadobutrol Injection
15 mmol/15 mL
****(1 mmol/mL)

For Intravenous Administration
Single-Dose Vial
Discard Unused Portion.
Sterile Solution

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INDICATIONS & USAGE SECTION

Highlight: Gadobutrol injection is a gadolinium-based contrast agent indicated for use with magnetic resonance imaging (MRI):

• To detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system in adult and pediatric patients, including term neonates (1.1)
• To assess the presence and extent of malignant breast disease in adult patients (1.2)
• To evaluate known or suspected supra-aortic or renal artery disease in adult and pediatric patients, including term neonates (1.3)
• To assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery
  disease (CAD). (1.4).

1 INDICATIONS AND USAGE

1.1 Magnetic Resonance Imaging (MRI) of the Central Nervous System (CNS)

Gadobutrol injection is indicated for use with magnetic resonance imaging (MRI) in adult and pediatric patients, including term neonates to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.

1.2 MRI of the Breast

Gadobutrol injection is indicated for use with MRI in adult patients to assess the presence and extent of malignant breast disease.

1.3 Magnetic Resonance Angiography (MRA)

Gadobutrol injection is indicated for use in magnetic resonance angiography (MRA) in adult and pediatric patients, including term neonates, to evaluate known or suspected supra-aortic or renal artery disease.

1.4 Cardiac MRI

Gadobutrol injection is indicated for use in cardiac MRI (CMRI) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (CAD).

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NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

No carcinogenicity studies of gadobutrol have been conducted.

Gadobutrol was not mutagenic in in vitro reverse mutation tests in bacteria, in the HGPRT (hypoxanthine-guanine phosphoribosyl transferase) test using cultured Chinese hamster V79 cells, or in chromosome aberration tests in human peripheral blood lymphocytes, and was negative in an in vivo micronucleus test in mice after intravenous injection of 0.5 mmol/kg.

Gadobutrol had no effect on fertility and general reproductive performance of male and female rats when given in doses 12.2 times the human equivalent dose (based on body surface area).

13.2 Animal Toxicology and/or Pharmacology

Local intolerance reactions, including moderate irritation associated with infiltration of inflammatory cells was observed after paravenous administration to rabbits, suggesting the possibility of occurrence of local irritation if the contrast medium leaks around veins in a clinical setting [see Warnings and Precautions (5.5)].

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