The International Contrast Ultrasound Society (ICUS) has filed a petition with the U.S. Food and Drug Administration (FDA) urging the agency to remove boxed warnings from ultrasound contrast agents. ICUS believes the warnings are obsolete in light of clinical experience and recently released data on the safety of the agents.
The petition cites studies showing that ultrasound contrast agents are safe, improve patient care, reduce overall healthcare costs, speed up time to diagnosis, and reduce the length of hospital stays. The contrast agents present no known risk of kidney or liver damage and are expelled from the body within minutes, according to an ICUS press statement. In addition, contrast-enhanced ultrasound (CEUS) exams do not require patient sedation.
The risk-benefit ratio for the use of ultrasound contrast agents has changed dramatically since 2007, when the FDA first mandated the black box, according to the society, which represents cardiologists, radiologists, and other physicians and imaging professionals in approximately 60 countries. The organization's board recently voted to formally request FDA action on the black box warning.
There are currently three ultrasound contrast agents cleared for use in the U.S., all of which are required to carry boxed warnings:
- Definity from Lantheus Medical Imaging
- Lumason from Bracco Diagnostics
- Optison from GE Healthcare
The black box warnings are appropriate only as an indicator of the very highest level of risk associated with a product, but such an extreme level of risk isn't present in ultrasound contrast agents, ICUS said. The warning could "unduly deter" the use of ultrasound contrast agents when medically indicated.
The petition notes that the FDA has downgraded package insert contraindications three times since 2007 and removed a 30-minute monitoring requirement for patients with pulmonary hypertension or unstable cardiopulmonary conditions. More recently, the FDA approved new indications for use in additional patient populations.
Scientific evidence more clearly supports a warning in the "warnings and precautions" section, as the potential adverse reactions do not occur frequently enough to rise to the boxed warning standard, according to the petition.
