Following reports from doctors that the information resulting from the use of contrast agents could be life-saving, the FDA warning was relaxed in May.
The only two FDA approved echocardiography contrast agents are Optison, made by GE Healthcare, and Definity, made by Lantheus Medical Imaging.
So far, most of the reported problems involved patients given Definity. According to the FDA, GE’s Optison was not marketed from November 2005 to October 2007. GE Healthcare had voluntarily withdrawn Optison after an FDA inspection indicated problems with a contract manufacturer. Optison was then re-launched last year. GE has stated that there have been no reported serious side effects.
In documents released by the FDA, Lantheus stated that there have been under 300 reports of serious complications and that the mortality rate was small compared to the number of doses given – around two million – since Definity’s launch in 2001. The firm also reported that results from recent clinical trials show that doctors’ ability to make diagnoses have been improved through the use of Definity. Since October, the FDA has approved labelling changes for this contrast agent, which removed most of the warnings that had been added.
However, four more deaths in patients given Definity have been reported to the FDA since October 2007. According to the Agency, one patient, suffering congestive heart failure, died within five minutes of receiving the dose; another, who suffered cardiac arrest minutes after receiving a dose, was revived. ‘The FDA remains concerned about the accumulating safety data pertaining to marketed ultrasound contrast agents, and the labels for these products continue to contain a boxed warning that highlights the risk for serious cardiopulmonary reaction,’ the Agency stated.
Calling for further studies to determine the safety and effectiveness of the contrast agents, a panel of independent medical experts was appointed by the FDA to review the safety of contrast agents used in echocardiography as well as other experimental contrast agents that are focused on other uses, e.g. to detect liver problems. Initially, the panel is being familiarised with the overall issues involved, before the FDA seeks its advice in coming months.
The FDA is also working with the Optison and Definity producers to develop a risk assessment and management programme. This has prompted two new clinical studies.