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Micro-bubble Perflutren Contrast Agents (Definity and Optison) Associated with Deaths and Serious Cardiopulmonary Reactions - Updatety Update

July 17, 2008

The FDA issued an update concerning an association between the micro-bubble perflutren contrast agents, Definity (perflutren lipid microsphere) and Optison (perflutren protein-type A microspheres), and serious cardiopulmonary reactions and death following administration. The FDA originally issued a safety alert in October 2007 after receiving reports of 10 deaths and 190 serious, non-fatal reactions during or shortly following Definity (perflutren liquid microsphere) administration. One death and 9 serious, non-fatal reactions were also reported following Optison (perflutren protein-Type A microspheres for injection) administration. Most reactions were seen within 12 hours of administration and include respiratory arrest, loss of consciousness, convulsions, anaphylactoid reactions, arrhythmias, cardiac ischemia and hypotension.

Since issuing its original safety report in October 2007, the FDA has received additional reports of 5 deaths and 60 serious, non-fatal reactions following Definity administration. The 5 patients who died had underlying medical conditions. Three of these patients had cardiac arrest within 30 minutes following Definity administration. The non-fatal reactions were similar to the reactions described above from the October 2007 report. No additional deaths or serious, non-fatal reactions have been reported with Optison administration.

The manufacturers of Definity and Optison have revised the product labeling warnings section to reflect these risks. The Boxed Warnings and Contraindications sections have also been updated as follows:

  • UpdatedBoxed Warning
    • Monitor vital signs, cardiac rhythm and oxygen saturation in patients with unstable cardiopulmonary conditions or pulmonary hypertension for at least 30 minutes after administration of one of these agents
    • Keep equipment for resuscitation and trained personnel readily available
  • Updated Contraindications
    • Physician consensus and FDA-review of published reports found the benefit of using these diagnostic agents may outweigh the risk of a serious adverse reaction in some cases
    • Remains contraindicated in patients with cardiac shunts or hypersensitivity to agent
    • No longer contraindicated in patients with:
      • Unstable congestive heart failure
      • Acute myocardial infarction
      • Serious ventricular arrhythmias or QT prolongation
      • Respiratory failure
      • Severe emphysema, pulmonary emboli or compromised pulmonary arterial vasculature

Additional information is available at the following links:

Updated
July 17, 2008; October 15, 2007; University of Utah, Drug Information Service. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.