(008) Hypersensitivity Reactions with Ultrasound Contrast Agents in Patients with a History of Polyethylene Glycol Allergy

Publication Number: 1004

Background: Polyethylene glycol (PEG) is widely used in medical, biomedical, pharmaceutical, cosmetic, industrial, and food products. FDA received reports of serious adverse reactions in PEG-allergic patients who were administered PEG-containing ultrasound contrast agents (UCAs).

Objectives: To characterize hypersensitivity reactions to UCAs in patients with a history of PEG allergy.

Methods: We conducted a retrospective case series analysis, utilizing reports identified from the FDA Adverse Event Reporting System (FAERS) database, the literature, and Applicant data for all cases of UCAs reported through August 2020 describing both 1) onset of a hypersensitivity adverse event (anaphylaxis, angioedema, and hypersensitivity) within one day of exposure to a UCA and 2) past medical history of allergy to PEG.

Results: We identified 13 cases from FAERS (n=11), published medical literature (n=1), and Applicant data (n=1) that support a potential causal association for hypersensitivity and anaphylaxis in PEG-allergic patients exposed to UCAs that contain PEG. The majority of cases (n=9) contained regulatory serious outcomes* of death (n=2), hospitalization (n=5), life-threatening (n=3), and other serious (n=1). Time to onset of events occurred within 20 minutes for all cases, with seven of the cases occurring within 5 minutes of UCA administration. Treatment was documented for 12 cases and included antihistamines (n=9), corticosteroids (n=5), and epinephrine (n=5). Cases included several features supporting a causal association: short time-to-onset, biologic plausibility (PEG in microsphere), and documented allergy to PEG. We did not identify cases (i.e., serious hypersensitivity events) for PEG-allergic patients exposed to the UCA perflutren protein-type A microspheres, a non-PEG containing product.

* A case may have more than one serious outcome.

Conclusions: In conclusion, we believe the evidence from the case series suggests a potential causal association between the PEG-containing UCAs and serious hypersensitivity reactions including anaphylaxis among PEG-allergic patients. The history of PEG allergy likely identifies a population who should avoid use of these products. FDA worked with the sponsors to update the prescribing information for these diagnostic agents and communicated findings and prescribing information directly to professional and clinical organizations.