Abstract:

Objective

To analyze and summarize the adverse reactions associated with three ultrasound contrast agents （Optison， Definity， and Lumason）， in order to provide reference information for optimizing clinical practice.

Methods

Adverse event （ADE） reports on Optison， Definity， and Lumason from January 1， 2004 to December 31， 2022 were extracted from the FDA Adverse Event Report System（FAERS）， and the basic characteristics of the reports were obtained. The reporting odds ratio （ROR） method and the UK Medicines and Healthcare Products Regulatory Agency （MHRA） comprehensive standard method were used to detect the adverse drug reaction （ADR） signals at the preferred term （PT） level and the standard MedDRA query （SMQ） level to evaluate the safety of the three ultrasound contrast agents.

Results

The FAERS database contained 1661 ADR reports related to the three ultrasound contrast agents， with 31， 1523，and 107 ADE reports related to Optison， Definity， and Lumason， respectively. Overall， there were more male patients （811） than female patients （693） in ADE reports， the main age group was 45 years and older （994），and Lumason had the highest percentage of fatal case reports （8.41%）. In ADR signal detection， positive signals were detected in 1 PT and 5 SMQs for Optison， in 58 PTs and 10 SMQs for Definity， and in 37 PTs and 10 SMQs for Lumason. In the PT level ADR signal detection， 3 new signals （pre-syncope， cyanosis，and loss of stimulus response） which were not recorded in the label were detected for Definity， and 8 new signals （pallor， pre-syncope， hyperhidrosis， burning sensation， pulmonary edema， heat sensation， pulmonary embolism， and product reconstitution quality problems） were detected for Lumason. The results of ADR detection at the SMQ level suggested that anaphylactic reaction-related diseases and shock disorders were risk characteristics shared by ultrasound contrast agents.

Conclusion

All three ultrasound contrast agents have potential ADR risks， and there are commonalities and differences among their ADR symptoms. Medical personnel should closely monitor patients during ultrasonography and promptly manage ADR that occur to ensure patient safety.

Key words: Ultrasound contrast agents, Pharmacovigilance, Adverse drug reactions, Data mining