001867 - Excipients under suspicion: A diagnosis challenge in adverse reactions to drugs and vaccines. A case report

BACKGROUND: Excipients are substances incorporated into medical substances to facilitate their formulation and administration, improving stability and bioavailability. It has been described that some of them can be responsible for adverse reactions. Most commonly implicated excipients include gelatine, polyethylene glycol (PEG) and related products such as polysorbate 80.

METHODS: We report the case of a 56-years-old woman, vaccinated with three SARS-CoV-2 doses in 2021 and 2022 that produced local skin allergic reaction. She was recently diagnosed with stage III Squamous Cell Lung Carcinoma. During the first chemotherapy cycle and after the administration of 18 mL of paclitaxel, the patient reported generalized pruritus, mild dyspnea, transient loss of consciousness, without skin lesions and vital constants within range, therefore the drug was suspended and parenteral corticosteroids and antihistamines were administrated, achieving rapid improvement of the symptoms; subsequent carboplatin administration was well tolerated. A week later, shortly during the administration of intravenous fosaprepitant, the patient developed severe hypotension, oxygen desaturation and confusion, requiring intramuscular adrenaline with complete recovery.

RESULTS: Skin prick test (SPT) was performed with PEG 400, PEG 4000, PEG 3350, Polysorbate 80 and trometamol: were positive for PEG 3350 (8 mm x 5mm) and PEG 4000 (6 mm x 5 mm).

Paclitaxel contains polyoxyethylene castor oil and dehydrated alcohol, while fosaprepitant contains polysorbate 80 as an excipient. Polysorbate 80 is a synthetic non-ionic surfactant which principal component is polyoxyethylene-20-sorbitan monooleate, which is structurally similar to PEGs. The SPT with polysorbate 80 was negative, but allergy to this component cannot be ruled out, as the commercial extract of polysorbate 80 had been open for some time.

An alternative formulation, which lacks polysorbate 80 and polyoxyethylene castor oil, is nab-paclitaxel; which was subsequently tolerated, after prior administration of ondansetron and dexamethasone. The absence of these excipients in these drugs would explain the patient's tolerance. The COVID-19 mRNA vaccines contain PEG 2000 in their formulation, which could explain a previous sensitization to this compound.

CONCLUSION: Suspicion of hypersensitivity to these excipients should be raised, particularly when the patient has experienced various reactions associated with multiple chemically distinct drugs.