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Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database

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Abstract

Introduction

Perflutren microbubble/microsphere ultrasound contrast agents have a black-box warning based on case reports of serious cardiopulmonary events. There have been several subsequent observational safety studies. Large spontaneous reporting databases may help detect/refine signals of rare adverse events that elude other data sources/study designs.

Objective

The objective of this study was to supplement existing knowledge of the reported safety of perflutren using statistical analysis of spontaneous reports.

Methods

We analyzed information from the US Food and Drug Administration Adverse Event Reporting System using a disproportionality analysis. Analysis of overall reporting for perflutren was supplemented by subset (age, indication) analysis. A signal of disproportionate reporting (SDR) was defined as EB05 >2.

Results

Overall, 18/380 Preferred Terms and 1/83 Standardized Medical Queries had SDRs. Most were small (EB05 = 2–4). Back pain and flank pain were the largest SDRs followed by events compatible with signs/symptoms of hypersensitivity. The general pattern of SDRs in the subset analysis was consistent with the overall analysis. Almost all events with SDRs were literally or conceptually labeled. Except for chest pain (higher in the age <65 years subgroup) and back pain (higher in the age ≥65 years subgroup), there were no statistically significant differences between age subsets. Except for the Preferred Terms Pruritus and Urticaria and the narrow Standardized Medical Queries Ventricular tachyarrhythmia, Angioedema, Oropharyngeal allergic conditions, and Hypersensitivity (higher in the stress test subgroup), there were no statistically significant reporting differences between indication subsets. There were no SDRs associated with the major cardiovascular events of death, myocardial infarction/ischemia, angina, arrhythmias, or convulsions in any analysis.

Conclusions

Our combined signal detection/evaluation analysis did not identify SDRs of novel adverse events or major cardiovascular events associated with perflutren ultrasound contrast agents. The negative results for major cardiovascular events extend previous signal evaluation exercises supporting the relative cardiovascular safety of these agents.

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Acknowledgments

Lauren Rosenberg, M.D., who assisted in the preparation of this manuscript.

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Authors and Affiliations

  1. New York University Medical Center, New York, NY, USA

    Manfred Hauben & Sripal Bangalore

  2. Mount Sinai School of Medicine, New York, NY, USA

    Kelly C. Hanretta

  3. Pfizer, Incorporated, 219 East 42nd Street, New York, NY, 10017, USA

    Manfred Hauben, Eric Y. Hung & Vincenza Snow

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  1. Manfred Hauben
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  2. Eric Y. Hung
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Correspondence to Eric Y. Hung.

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Funding

No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Manfred Hauben, Eric Hung, and Vincenza Snow are employees and stockholders of Pfizer, Incorporated. Manfred Hauben holds stocks in General Electric, a subsidiary of which, GE Healthcare, markets the ultrasound contrast agent OPTISON™. Manfred Hauben, Eric Hung, Vincenza Snow, Kelly C. Hanretta, and Sripal Bangalore have no other conflicts of interest that are relevant to the content of this study.

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Hauben, M., Hung, E.Y., Hanretta, K.C. et al. Safety of Perflutren Ultrasound Contrast Agents: A Disproportionality Analysis of the US FAERS Database. Drug Saf 38, 1127–1139 (2015). https://doi.org/10.1007/s40264-015-0332-6

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