Eri Yasue, Takunori Ogawa, Yuto Mano, Tetsuro Takeuchi, Koharu Harada, Yoshifumi Kimizuka
Oral triazoles, particularly itraconazole and voriconazole (VRCZ), are key antifungal agents for chronic pulmonary aspergillosis (CPA); however, hypersensitivity reactions to triazole antifungals can limit their use. We describe a 74-year-old man with CPA who developed immediate-type hypersensitivity reactions to both oral VRCZ and itraconazole. Because these oral formulations contain no excipient cyclodextrin, the reactions were attributed to the triazole drug substance, consistent with class cross-reactivity. After exhausting alternative antifungal options, VRCZ desensitization was undertaken. An intravenous route was selected as it allows precise dose titration and immediate interruption if required during rapid drug desensitization (RDD), with subsequent transition to oral therapy. The intravenous formulation of VRCZ additionally contains sulfobutyl ether β-cyclodextrin sodium, whose rapid infusion can provoke infusion-related reactions; the prescribing information therefore limits the infusion rate to ≤ 3 mg/kg/h. We modified a previously published RDD protocol to preserve the same cumulative target dose while strictly limiting infusion rate to ≤ 3 mg/kg/h, using only two diluted concentrations and adjusting the infusion rate alone. Desensitization was initiated at 0.05 mg (1/6000 of the planned dose) and escalated through 11 steps at 15-min intervals, with prolongation of the final step to remain within the infusion-rate recommendation. No hypersensitivity reactions occurred during desensitization. The patient subsequently tolerated maintenance intravenous VRCZ, which was switched to the same oral dose. Clinical symptoms improved, and follow-up imaging showed regression of the pulmonary lesion. Distinguishing triazole drug-substance hypersensitivity from excipient-related infusion risk, and controlling the infusion rate accordingly, may improve the safety of intravenous triazole desensitization.