FDA approves Bayer's Gadavist® (gadobutrol) injection as the first magnetic resonance contrast agent for pediatric patients less than 2 years of age

LEVERKUSEN, Germany, Jan. 5, 2015 /PRNewswire/ -- Bayer HealthCare announced today that the U.S. Food and Drug Administration (FDA) has approved Gadavist^® (gadobutrol) injection for use with magnetic resonance imaging (MRI) in pediatric patients less than 2 years of age, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system.¹ Gadavist was previously approved for this use in patient populations over the age of 2. The FDA's priority review was based on a study showing that the pharmacokinetic (PK) and safety profiles in pediatric patients less than 2 years of age were similar to that of older children and adults at standard dose (0.1 mmol/kg).¹

"Until this study, there were limited data regarding the use of gadolinium-based contrast agents in pediatric patients younger than 2 years of age, and there has been a significant need to better understand how they work in our youngest patients," said Dr. Ravi Bhargava, study investigator and pediatric radiologist, University of Alberta, Edmonton, Canada. "Ultimately, it's important for us to have safe and effective tools to help us accurately detect abnormalities and visualize areas of the central nervous system in children of all ages."

"Gadavist is the first FDA-approved gadolinium-based contrast agent for pediatric patients under 2 years of age, including term neonates, and the approval provides guidance to physicians on how to use Gadavist in these young patients," said Christiane Pering, Chief Medical Officer (CMO) and Head of Innovation within Bayer HealthCare's  Medical Care division.  "With this label expansion, Gadavist is appropriate to use for MRI of the central nervous system at a standard dose of 0.1mmol/kg for patients of all ages – term neonates to adults."

About Pharmacokinetics
Pharmacokinetics (PK) is the study of the movement of a drug in the body, including the process of distribution and elimination, and it is dependent on patient-related factors, as well as the drug's chemical properties.

About the Study
The study enrolled 47 pediatric patients with ages spanning from term neonates to 23 months with normal renal function from nine centers across the U.S., Canada and Europe. Forty-four pediatric patients were evaluated for safety and efficacy and 43 were eligible for a PK profile evaluation, including nine term neonates less than 2 months of age.¹  Safety was a secondary endpoint and the study also included a qualitative assessment of efficacy.¹

The data showed that the Gadavist PK profile in pediatric patients under 2 was similar to the PK profile in older pediatric patients and adults. Investigators also observed a similar safety profile for Gadavist in this pediatric population.¹

The study found that the Gadavist adverse event (AE) profile was consistent with what has been seen in older populations. In one patient, vomiting was reported as a mild adverse drug reaction (ADR) to Gadavist. The most common non-serious AEs unrelated to Gadavist were cough, nasopharyngitis, rhinitis, pyrexia and vomiting. Serious AEs were unrelated to Gadavist and were reported in three out of 44 patients.¹

About Gadavist
Gadavist (gadobutrol) injection was first approved in the U.S. in March 2011 for intravenous use in diagnostic MRI in adults and children (2 years of age and older) to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. Gadavist was further approved in June 2014 in the U.S. for MRI of the breast to assess the presence and extent of malignant breast disease.

Gadavist, also known as Gadovist^® and Gadovist^® 1.0 in other regions, is the U.S. brand name of the aqueous 1.0M solution of gadobutrol, a gadolinium (Gd)-based extracellular contrast agent for MRI with a macrocyclic structure. The safety profile of Gadavist has been established in clinical trials involving 6,330 patients. Please see Important Safety Information, including Boxed Warning below.

IMPORTANT SAFETY INFORMATION¹

WARNING: NEPHROGENIC SYSTEMIC FIBROSIS (NSF)

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 fibrosis affecting the skin, muscle and internal organs.

• The risk of NSF appears highest among patients with:
  • Chronic, severe kidney disease (GFR<30mL/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 (for example, 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 Gadavist dose and allow a sufficient period of time for elimination of the drug from the body prior to any re-administration. 

Contraindication and Important Information about Hypersensitivity Reactions:
Gadavist is contraindicated in patients with history of severe hypersensitivity reactions to Gadavist. Anaphylactic and other hypersensitivity reactions with cardiovascular, respiratory, or cutaneous manifestations, ranging from mild to severe, including death, have uncommonly occurred following Gadavist administration. Patients with any history of a reaction to contrast media, bronchial asthma, and/or allergic disorders may have an increased risk for a hypersensitivity reaction to Gadavist.

Acute Kidney Injury: In patients with chronic renal impairment, acute kidney injury sometimes requiring dialysis has been observed with the use of some GBCAs. Do not exceed the recommended dose; the risk of acute kidney injury may increase with higher than recommended doses.

Extravasation and Injection Site Reactions: Ensure catheter and venous patency before the injection of Gadavist. Extravasation into tissues during Gadavist administration may result in moderate irritation. Avoid intramuscular administration of Gadavist.

Overestimation of Extent of Malignant Disease in MRI of the Breast: Gadavist MRI of the breast overestimated the histologically confirmed extent of malignancy in the diseased breast in up to 50% of the patients.

Adverse reactions: The most frequent adverse reactions (>0.5%) associated with Gadavist in clinical studies were headache (1.5%), nausea (1.2%), and dizziness (0.5%).

Please see full prescribing information at
http://labeling.bayerhealthcare.com/html/products/pi/gadavist_PI.pdf

About Bayer HealthCare
The Bayer Group is a global enterprise with core competencies in the fields of health care, agriculture and high-tech materials. Bayer HealthCare, a subgroup of Bayer AG with annual sales of EUR 18.9 billion (2013), is one of the world's leading, innovative companies in the healthcare and medical products industry and is based in Leverkusen, Germany. The company combines the global activities of the Animal Health, Consumer Care, Medical Care and Pharmaceuticals divisions. Bayer HealthCare's aim is to discover, develop, manufacture and market products that will improve human and animal health worldwide. Bayer HealthCare has a global workforce of 56,000 employees (Dec. 31, 2013) and is represented in more than 100 countries. More information at www.healthcare.bayer.com.
 

Forward-Looking Statements
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer Group or subgroup management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer's public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments

References
1. Gadavist^® (gadobutrol) Prescribing Information. Whippany, New Jersey, USA: Bayer Healthcare Pharmaceuticals, Inc.

PP-325-US-0062    December 2014

SOURCE Bayer HealthCare

Related Links

http://www.healthcare.bayer.com