FDA Urged to Nix Black Box Label for Ultrasound Contrast Agents

September 1, 2020

Grassroots group points to substantial clinical evidence of safety in call for agency to remove the warning.

Citing significant clinical evidence of safety, a multi-institutional, grassroots group has asked the U.S. Food and Drug Administration (FDA) to remove the black box warning from ultrasound contrast agents (UCAs), calling the label “outdated.”

These radiation-free agents are made of biocompatible suspensions that present no known risks for kidney or liver damage, and the body expels them within minutes. Extensive, new medical data shows UCAs are extremely safe and beneficial across a myriad of patient groups and uses. Consequently, the group said, they should not carry the heftiest FDA caution.

“Removing this ‘black box’ will help patients across American access safer, more reliable, and more cost-effective diagnostic imaging, while speeding up the introduction of appropriate therapy and saving lives,” the International Contrast Ultrasound Society (ICUS) wrote in its Citizens Petition to the FDA.

The FDA removes a black box warning when clinical evidence reveals the risks and safety concerns of a product are less severe than originally believed. Since first introducing this label for UCAs in 2007, the agency is softened its warning somewhat over time, but the ICUS has called for more.

“The current labeling is outdated and may harm patients by unduly deterring the use of UCAs in patients who would benefit from an enhanced ultrasound scan,” said Steven Feinstein, M.D., ICUS co-president, professor of medicine at Rush University Medical Center, and expert in cardiac contrast-enhanced ultrasound (CEUS).

UCAs are made up on biocompatible suspensions of tiny gas-filled bubbles that are administered intravenously during an ultrasound exam. The resulting high resolution can make it substantially easier to identify heart disease, stratify heart attack or stroke risk, and identify, characterize, and stage liver, kidney, prostate, breast, and other organ system tumors, said the ICUS, a non-profit medical society that includes radiologists, cardiologists, and other ultrasound imaging professionals. Additionally, when using UCAs, it is not necessary to sedate patients for a CEUS exam which is often comparable to CT and MRI exams when examining kidney and liver lesions.

“It is now abundantly clear that UCAs are extremely safe, and that they may save lives and lower overall diagnostic imaging costs,” said Michael Main, M.D., a cardiologist, ICUS vice president and co-executive medical director of Saint Luke’s Mid America Heart Institute.

Using UCAs in CEUS exams offers several benefits, the team said. These exams can help patients avoid additional downstream tests, as well as control overall healthcare costs, shorten hospital says by accelerating time to diagnosis and treatment, and improve efficiency. Ultimately, they said, it can alter patient outcomes and save lives.

Currently, there are three UCAs approved for use in the United States – Definity (Lantheus Medical Imaging), Lumason (Bracco), and Optison (GE healthcare).

According to the ICUS petition, a number of other major ultrasound organizations and individual CEUS experts joined the group is petitioning the FDA to make this change. Maintaining the black box labeling on UCAs, they said, could deter use and ultimately harm patient care.

“Removing this ‘black box’ will help patients across American access safer, more reliable and more cost-effective diagnostic imaging, while speeding up the introduction of appropriate therapy and saving lives,” they wrote. “The public interest – as well as the FDA’s own standards – demand nothing less.”