Hashmi Yusra, Memon Shehzeen F, Khan Yasir A, Jabbar Naeem, Mansoor Neelum
Pediatric Oncology, The Indus Hospital, Karachi, PAK.
Internal Medicine, Dow University of Health Sciences, Karachi, PAK.
Cureus. 2021 Feb 14;13(2):e13337. doi: 10.7759/cureus.13337.
All-trans retinoic acid (ATRA) is a derivative of vitamin A and is the mainstay treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare yet important side-effect of ATRA, especially when it is used concomitantly with a medication that impedes its metabolism by inhibiting cytochrome P-450 in the liver and thus increasing the duration of exposure to ATRA. Azole antifungal drugs such as voriconazole are frequently used in patients undergoing chemotherapy due to a high incidence of fungal infections. These medications inhibit two vital enzymes of cytochrome P-450, CYP2C9 and CYP3A4, potentiating the effects of ATRA on calcium metabolism. We present a case of a nine-year-old girl who underwent chemotherapy with all-trans retinoic acid for acute promyelocytic leukemia. The patient was given an anti-fungal cover with voriconazole for extensive fungal chest infection simultaneously. She was found to have asymptomatic hypercalcemia on routine follow-up during the consolidation phase. Both medications were stopped. Subsequently, she was admitted to the ward and managed conservatively with hydration. Serum calcium levels were returned to normal within six days after stopping the combination of ATRA and voriconazole. We underscore that the use of anti-fungal medications should be limited while using ATRA. However, strict monitoring must be done when a combination of these drugs is started, if necessary.
全反式维甲酸（ATRA）是维生素A的衍生物，是急性早幼粒细胞白血病（APL）的主要治疗药物。高钙血症是ATRA一种罕见但重要的副作用，尤其是当它与一种通过抑制肝脏中的细胞色素P - 450来阻碍其代谢从而增加ATRA暴露时间的药物同时使用时。由于真菌感染发生率高，唑类抗真菌药物如伏立康唑常用于接受化疗的患者。这些药物抑制细胞色素P - 450的两种重要酶CYP2C9和CYP3A4，增强了ATRA对钙代谢的影响。我们报告一例9岁女孩，她因急性早幼粒细胞白血病接受全反式维甲酸化疗。该患者因广泛的肺部真菌感染同时接受了伏立康唑抗真菌治疗。在巩固期的常规随访中发现她有无症状高钙血症。两种药物均停用。随后，她被收入病房并通过补液进行保守治疗。停用ATRA和伏立康唑联合用药后6天内血清钙水平恢复正常。我们强调，在使用ATRA时应限制抗真菌药物的使用。然而，如果有必要，在开始联合使用这些药物时必须进行严格监测。
