Investigating Etoposide Adverse Reactions Associated with Polyethersulfone Filter

Cancer drugs administered intravenously have an inherent associated risk of acute, severe, and potentially life-threatening allergic reaction, also known as anaphylaxis, for patients receiving them. In a study consisting of 5584 patients, the person-based lifetime incidence of severe anaphylaxis for patients receiving at least 1 intravenous chemotherapy was 0.48%. In addition, the administration-based incidence was 0.031%.¹

Pharmacists and physicians identified an uptick in etoposide infusion reactions possibly as result of a protocol change to use inline filters in the clinical setting. The clinical team sought the assistance of outside experts with a specialized skillset and equipment to perform an in-depth analysis for their concern.²

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Researchers conducted a multidisciplinary follow-up analytical study to determine the chemical structure of etoposide pre- and post-passage through a hydrophilic polyethersulfone filter in a clinical setting. They prepared a final concentration of 0.4 mg/mL by adding etoposide 100 mg/5mL to a 250-mL bag of 0.9% sodium chloride. Etoposide’s prescribing information recommended a maximum concentration of 0.4 mg/mL to minimize risk of precipitation. They primed the infusion set (i.e., filter and tubing) with etoposide solution to completely saturate the in-line filter and expose it to the solution. They collected triplicate 5 mL samples from the following locations: 1) the injection port of the compounded IV bag, 2) a needle-less access port on the tubing located before the in-line filter, and 3) needle-less access port after the in-line filter.²

The research team immediately analyzed the samples using high-performance liquid chromatography diode array detection mass spectrometry (HPLC-DAD-MS/MS) for any possible degradation, metabolite formation, or excipients.²

They noted 2 key findings: First, HPLC-DAD-MS/MS did not detect a measurable difference between pre- and post-filter etoposide infusion samples. Second, the absence of a chemical change of etoposide fails to consider for interactions between other components of the infused solution and the filter.²

The researchers suggested possible explanations contributing to increases in etoposide infusion reactions due to inline filter use. One possibility is that the presence of benzyl alcohol in the etoposide infusion might interact with the polyethersulfone member used in the IV-5 filter. The method utilized for filter sterilization could be another contributing factor causing an increase in infusion reactions.²

The researchers noted it is unlikely that a chemical change of etoposide is due to a change of inline filters, and not a cause for an increase in infusion reactions. Additionally, this study showed the importance of a multidisciplinary team’s expertise to investigate a clinical inquiry beyond the scope of the clinicians’ skillset and their access to necessary technology.²

References

1. Miles N, Masters A, Desta Z, Goldman JL, Suppes SL, Tillman EM. Multidisciplinary Approach to Deciphering Etoposide Infusion Reactions and Potential Role of Polyethersulfone Filter Membranes. J Pediatr Pharmacol Ther. 2023;28(7):643-648.

2. Horita N, Miyagi E, Mizushima T, et al. Severe anaphylaxis caused by intravenous anti-cancer drugs. Cancer Med. 2021;10(20):7174-7183.