Infusion reactions following administration of intravenous rolapitant at an academic medical center

Abstract

In 2017, due to a fluid shortage secondary to Hurricane Maria's devastation of Puerto Rico, hospitals and health-systems began to substitute rolapitant for fosaprepitant as part of chemotherapy-induced nausea and vomiting prevention and treatment strategies. However, despite advantageous pharmacologic and formulation (e.g. long half-life, quicker time to onset, and lack of first-pass hepatic metabolism) profiles, there seems to be significant risk of infusion-related hypersensitivity reactions associated with the administration of intravenous rolapitant. In January 2018, the U.S. FDA issued a Health Care Provider Letter stating that anaphylaxis, anaphylactic shock, and other serious hypersensitivity reactions have been reported in the postmarketing setting. Importantly, these reactions were observed at a higher rate than initially reported in the phase 1 bioequivalence study that led to FDA approval of intravenous rolapitant (2.8%), with many resulting in hospitalizations. At our institution, rolapitant-induced infusion-related reactions also occurred in more patients than expected (8.7%). Described herein are six cases of infusion-related hypersensitivity reactions with intravenous rolapitant at the North Carolina Cancer Hospital. Due to the quick onset of the infusion-related hypersensitivity reactions with intravenous rolapitant, interpatient differences in pharmacokinetics or pharmacodynamics are unlikely to be the cause. An objective assessment utilizing the Naranjo Causality Scale rates these infusion-related hypersensitivity reactions as definite adverse drug reactions.