First US Injection of MR Contrast Agent Gadoterate Meglumine Performed

In July 2013, US radiologists performed the first injection of gadoterate meglumine (Dotarem), the only macrocyclic and ionic gadolinium-based contrast agent (GBCA) approved by the US Food and Drug Administration (FDA). The procedure was performed in a school-age child.

Dotarem is indicated for intravenous use (IV) with magnetic resonance imaging (MRI) in spine, brain (intracranial), and associated tissues in adult and pediatric patients (two years of age and older) to identify and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity.

“The availability of a macrocyclic and ionic gadolinium-based contrast agent that is FDA-approved for use in children ages 2–18 is very desirable,” said Dr. Daniel Podberesky, chief of thoracoabdominal imaging in the department of radiology, Cincinnati Children’s Hospital Medical Center (OH, USA),where the procedure was done.

Dotarem, developed by Guerbet (Villepinte, France), was approved by the FDA in March 2013, and was released for the US market in early July. Cincinnati Children’s was the first hospital to order the product in the United States. In 2012, Cincinnati Children’s performed 18,000 total MRI scans, with more than 6,600 performed as contrast-enhanced MRI scans.

“We are extremely pleased that Cincinnati Children’s Hospital Medical Center is the first hospital to use Dotarem to enhance an MRI procedure,” said Massimo Carrara, general manager, Guerbet US. “This reinforces the need for this product.”

Dotarem, which has been widely marketed outside the United States since 1989 and more than 37 million doses administered, is the only macrocyclic and ionic GBCA. The recommended dose is 0.2 mL/kg (0.1 mmoL/kg) body weight (BW). Dotarem Injection 0.5 mmol/mL contains 376.9 mg/mL of gadoterate meglumine, and is available in vials and prfilled syringes.

MRI has become the gold standard of central nervous system (CNS) imaging since its introduction over 20 years ago. It is estimated that there were more than 10 million contrast-enhanced MRI scans performed in the United States in 2011, with about 60% of these examinations performed to image the CNS.

The Dotarem new drug application (NDA) included two phase III clinical studies. These studies evaluated the diagnostic efficacy and safety of Dotarem for intravenous use with magnetic resonance imaging (MRI) in brain (intracranial), spine, and associated tissues in adult and pediatric patients (two years of age and older) to detect and visualize areas with disruption of the blood brain barrier (BBB) and/or abnormal vascularity. Both phase III studies assessed the better quality of the enhanced images over the unenhanced images for CNS lesion visualization in all three co-primary endpoints. All defined primary and key secondary efficacy analyses were met and support the effectiveness of Dotarem at a standard dose of 0.1 mmol/kg BW. In addition to these two studies, 21 supportive clinical studies evaluated the efficacy and safety of Dotarem-enhanced MRI.

Commercialized widely in over 70 countries in Europe, Asia, Africa, Middle East, and South America, more than 37 million doses of Dotarem have been administered. The approved indications for Dotarem may vary between countries. Dotarem is the leading contrast agent in Europe with 47% market share in 2012.

A pioneer in the field of contrast agents with more than 80 years of experience, Guerbet is the only pharmaceutical group fully dedicated to medical imaging worldwide. As such, it has a complete offering of contrast products for X-ray and MRI and for interventional radiology, along with a range of injectors and related medical equipment to provide improved diagnosis and treatment of patients.

To promote the discovery of new products and assure future growth, Guerbet allocates substantial resources to research and development every year (approximately 10% of sales). Guerbet also markets other contrast agents in the United States.

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 noncontrasted MRI or other modalities. NSF may result in fatal or debilitating fibrosis affecting the skin, muscle, and internal organs.

Related Links:
Cincinnati Children’s Hospital Medical Center
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