5PSQ-027 Oral tolerance induction to cotrimoxazole in immunosuppressed patients with a history of a non-severe hypersensitivity reaction

<h3>Background and Importance</h3> Cotrimoxazole (CTX) is the first-line therapy used to prevent and treat <i>Pneumocystis jirovecii</i> pneumonia (PJP). In the case of a previous non-severe hypersensitivity reaction to CTX, oral tolerance induction may be used instead of alternative therapies – pentamidine, dapsone or atovaquone. <h3>Aim and Objectives</h3> The aim of this study was to establish a management protocol for oral induction of tolerance to CTX in patients with a history of non-severe hypersensitivity reactions. <h3>Material and Methods</h3> Information on CTX hypersensitivity reactions and their management was gathered from published literature, databases, and consultations with an allergist. Protocols for tolerance induction were proposed, and a list of pharmaceutical excipients in available CTX-containing medications, which may contribute to drug reactions, was compiled. Data on patients undergoing oral CTX tolerance induction were collected from the hospital information system in two institutions. <h3>Results</h3> Due to limited relevant publications – mainly addressing CTX hypersensitivity management in HIV/AIDS patients – and lacking a standardised protocol, we adapted single-day and multi-day protocols from existing studies. The single-day protocol suits patients with non-severe skin reactions, while the multi-day protocol is used for more severe reactions and can also be applied in outpatient settings for non-severe cases. Protocol choice must be strictly individualised based on patient condition and reaction severity. Severe reactions require basophil activation and skin tests, followed by an oral provocation test with a full therapeutic CTX dose under observation and preparedness to manage anaphylaxis. We compiled a list of CTX product excipients, noting that generic substitution often improved tolerance. Pharmacists proposed alternative preparations during oral suspension shortages for optimal desensitisation dosing. To prevent loss of tolerance during PJP prophylaxis, especially if CTX administration is interrupted for over three days, we recommend administering CTX three times a week, every other day, or daily. Oral induction is contraindicated in severe delayed-type hypersensitivity reactions, Stevens-Johnson syndrome, or acute generalised exanthematous pustulosis. Since implementing local protocol, nine immunocompromised patients were successfully delabeled from CTX allergy using oral desensitisation or generic substitution. <h3>Conclusion and Relevance</h3> The prevalence of hypersensitivity reactions to CTX in the population is lower than reported in patient’s medical history. Multidisciplinary collaboration is essential for rational treatment and effective prophylaxis of PJP infections. <h3>References and/or Acknowledgements</h3> <h3>Conflict of Interest</h3> No conflict of interest