Attention to the interactions between vincristine and triazole antifungals: perspectives from real-world retrospective analysis and pharmacovigilance assessment

BACKGROUND: In patients with hematologic malignancies, the combination of triazole antifungals and vincristine can lead to severe neurological toxicity. We attempted to assess the adverse events (AEs) associated with these interactions, particularly ileus. RESEARCH DESIGN AND METHODS: We retrieved AEs data from FAERS database (2004-2023) focusing on the combination of four triazoles (fluconazole, itraconazole, voriconazole, posaconazole) with vincristine. Case reports of AEs were collected for retrospective analysis up to 31 December 2023. RESULTS: The FAERS database indicated that neurological and gastrointestinal systems were most commonly involved systems when combined use triazole antifungals and vincristine, with ileus being the most frequently reported AE. The highest signal strengths for ileus were with itraconazole. AEs associated with concomitant use of triazole antifungal drugs and vincristine were identified through retrospective analysis of 42 clinical case reports, of which itraconazole, posaconazole, and voriconazole were involved in 66.7%, 28.6%, and 4.8% of cases, respectively. Patients who received the two-drug combination experienced AEs within one month in 88.1% of cases. Almost all patients improved within one month after discontinuing or switching antifungal drugs. CONCLUSIONS: Ileus is the most common AE associated with the combination of triazole antifungals and vincristine, with itraconazole showing the highest risk.