North Billerica, MA - The US FDA has approved less ominous and restrictive language for the labeling of the echocardiographic contrast agents perflutren lipid microspheres injectable suspension (Definity, Lantheus Medical Imaging) and perflutren protein-type A microspheres for injection (Optison, General Electric). The changes come after the agency added new warnings and contraindications to the labeling late last year.

The latest wording addresses concerns raised with the FDA by the cardiology community after the agency, in October 2007, added warnings and contraindications to the labeling that may not have been justified. As subsequently reported by heartwire, the new language warned users of "serious cardiopulmonary reactions occurring within 30 minutes of product administration" and noted that the products are "contraindicated in patients with unstable cardiopulmonary status, including those with unstable angina, acute MI, respiratory failure, and recent worsening of congestive heart failure."

Experts weighing in on the new wording vehemently disagreed with the agency's interpretation of the evidence, heartwire reported, and lamented that it would prevent the contrast agents' use in the very patients who would most benefit from them.

After receiving feedback from thought leaders in the field, the FDA reconsidered.

A press release issued today by Lantheus Medical Imaging [1], which described the new, less restrictive wording as it pertains to the product, says, "The decision by the FDA to revisit the changes it initially made to the Definity label last fall came after extraordinary advocacy by the global community of contrast ultrasound and echocardiography practitioners." It further notes that "Educational outreach by the echocardiography community to the FDA was instrumental in achieving this class label change."

The company's statement also states that similar changes are being made to the labeling of "all perflutren-containing microsphere contrast agents." Lantheus Medical Imaging is the company that evolved from the purchase of Bristol-Myers Squibb Medical Imaging, the previous owner of Definity, by an investment group earlier this year.

Definity's labeling, Lantheus says, now reads, "Do not administer Definity to patients with known or suspected right-to-left, bidirectional, or transient right-to-left cardiac shunts, or hypersensitivity to perflutren. Do not administer Definity by intra-arterial injection." It also says that "All other contraindications have been removed."

According to Lantheus, "The boxed 'warning' and 'warnings' sections have been revised to reflect monitoring only in patients with pulmonary hypertension or unstable cardiopulmonary conditions, as compared with the previous label, which included language regarding monitoring in all patients."

[Editor's note: The FDA's announcement of the new wording for both companies' products appears in a July 17, 2008 update to the October 2007 labeling revisions [2].]