Lin Mark John-Yung, Paul Megan Rose, Kuo Dennis John
J Pediatr Pharmacol Ther. 2018 Sep-Oct;23(5):417-420. doi: 10.5863/1551-6776-23.5.417.
Vincristine is a chemotherapeutic agent with a potential toxicity of sensorimotor peripheral neuropathy. Patients receiving chemotherapy are in an immunocompromised state and may require antifungal agents. Triazole antifungals are known inhibitors of cytochrome P450 (CYP) enzymes. Vincristine is a known CYP3A4 and CYP3A5 substrate, and concomitant administration with fluconazole or voriconazole has been reported to increase vincristine toxicity and peripheral neuropathy, but there is limited literature on posaconazole in this regard. This 5-year-old girl with pre-B-cell acute lymphoblastic leukemia received vincristine while receiving posaconazole for a mucormycosis infection and developed unexpectedly severe peripheral neuropathy. After recovery, the child continued on mucormycosis prophylaxis with posaconazole with instructions to hold for 2 days before and on the day of vincristine administration. This case illustrates the potentiating effect that posaconazole had on vincristine-associated neurotoxicity, and our approach to mitigating that negative interaction.
长春新碱是一种具有导致感觉运动性周围神经病变潜在毒性的化疗药物。接受化疗的患者处于免疫功能低下状态，可能需要使用抗真菌药物。三唑类抗真菌药是已知的细胞色素P450（CYP）酶抑制剂。长春新碱是已知的CYP3A4和CYP3A5底物，据报道，与氟康唑或伏立康唑同时使用会增加长春新碱的毒性和周围神经病变，但关于泊沙康唑在这方面的文献有限。这名5岁的前B细胞急性淋巴细胞白血病女孩在接受泊沙康唑治疗毛霉菌感染时同时接受长春新碱治疗，结果出现了意外严重的周围神经病变。康复后，该患儿继续使用泊沙康唑预防毛霉菌病，并收到指示在长春新碱给药前2天及给药当天停药。本病例说明了泊沙康唑对长春新碱相关神经毒性的增强作用，以及我们减轻这种负面相互作用的方法。
