Background: Drug hypersensitivity reactions commonly generate systemic syndromes but can also affect specific organs. Mepolizumab, a monoclonal antibody targeting interleukin-5, is a safe and effective Food and Drug Administration-approved biologic therapy for severe eosinophilic asthma. Case Presentation: A 49-year-old female developed acute pancreatitis complicated by acute hypoxic respiratory failure secondary to fluid overload. Following 72 hours of intravenous fluids and analgesic administration, an urticarial rash developed on the patient’s trunk, raising concern for a drug-related exanthem. After medication reconciliation, it was deemed that she had a hypersensitivity reaction to mepolizumab. Conclusion: In several clinical trials, mepolizumab demonstrated few hypersensitivity reactions. This patient presentation highlights the importance of strong clinical suspicion for drug hypersensitivities, especially in patients failing to respond to the standard of care for common medical conditions.

Keywords: allergy, hypersensitivity, mepolizumab, pancreatitis, DRESS