FDA regulators reported Friday that since October 2007 the agency has received four reports of patients dying after receiving injections of the drug Definity when used in medical imaging of the heart.
One patient with congestive heart failure died within five minutes of receiving the drug, according to a FDA report released ahead of an Advisory Committee meeting to be held June 24. In addition, the FDA said it received a report of a patient who had a cardiac arrest within minutes after a Definity injection, however, the patient was revived.
In October 2007, the agency added a black box warning on ultrasound contrast agents, after receiving about 200 reports of serious allergic reactions, seven of which resulted in death. The cardiac or pulmonary complications included problems such as cardiac arrest, heart rhythm problems, hypotension and hypoxemia. The warning affected Definity from Lantheus Medical Imaging (at the time sold by Bristol-Myers Squibb Medical Imaging) and Optison from GE Healthcare.
The agency noted that “post-marketing reports of serious adverse reactions over the recent past have mainly cited the use of Definity, since Optison was not marketed between November 2005 and late October 2007.”
Since October, the FDA has revised the U.S. the boxed warning, warnings and contraindications sections of the prescribing information on the product label for Optison and Definity vial for injectable suspension, which has caused the companies to update its labels. The agency said that the revision came as a result of physicians who reported that “the contrast agents may provide essential diagnostic information in some of these patients.”
The FDA said it has most recently been working with the Optison and Definity manufacturers to develop a risk assessment and management program, which has resulted in the commencement of two clinical studies.
The Associated Press reported that the FDA will ask a panel of outside experts to suggest safety requirements for developing better, safer imaging products at the meeting.
At the meeting, participants will be asked to consider the commencement of phase 3 studies that use eligibility criteria designed predominantly to optimize the assessment of diagnostic efficacy. However, the agency noted that these studies may exclude subjects with complex underlying conditions that may increase diagnostic variability.
The FDA said it has invited the Definity and Optison manufacturers to participate in the advisory committee. The FDA has also invited the manufacturer of a third ultrasound contrast agent, SonoVue, to participate in the advisory committee. SonoVue, a product marketed in Europe, consists of a core gas of sulphur hexafluoride and an outer shell of specific phospholipids. SonoVue is approved in Europe for use in echocardiography as well as for use in examination of the peripheral vasculature and for vascular assessments of liver and breast lesions, according to the agency.