Department of Hematology, Diskapi Yildirim Beyazit Training and Research Hospital, University of Health Sciences, Ankara, Turkey.
J Oncol Pharm Pract. 2021 Dec;27(8):2027-2029. doi: 10.1177/10781552211007889. Epub 2021 Apr 13.
All-trans retinoic acid (ATRA) is a physiological metabolite of vitamin A and it is used for the treatment of acute promyelocytic leukemia (APL). Hypercalcemia is a rare side effect of ATRA and it may be potentiated after interaction of ATRA with azole group antifungals. Herein, we have reported an APL case with hypercalcemia that is caused by the interaction of ATRA and posaconazole.
A 49-year-old female patient was diagnosed as APL after the examinations performed upon the detection of pancytopenia when she had presented with the complaints of widespread bruising and fever. After the initiation of posaconazole and ATRA, her serum calcium levels begin to increase (10.3 to 11.1mg/dl). Her vitamin D level was 21.9 ng/ml and PTH 17.8 pg/ml, both were in the normal ranges. The Drug Interaction Probability Scale score of our case was calculated as 6, indicating that the probable adverse drug reaction. Therefore, the high level of serum calcium was attributed to the interaction between ATRA and posaconazole.
MANAGEMENT & OUTCOME: Although hypercalcemia with ATRA and other antifungal agents have been previously reported in the literature, this is the first report of hypercalcemia with the concomitant use of ATRA and posaconazole.
This case highlights the importance of monitoring ATRA's side effects when it is used in combination with drugs inhibiting the cytochrome P450 enzymes. In conclusion, the concomitant use of posaconazole and ATRA may lead to hypercalcemia and serum calcium levels return to normal ranges with the discontinuation of these drugs.
全反式维 A 酸（ATRA）是维生素 A 的生理代谢产物，用于治疗急性早幼粒细胞白血病（APL）。高钙血症是 ATRA 的罕见副作用，它可能在 ATRA 与唑类抗真菌药物相互作用后增强。在此，我们报告了一例由 ATRA 与泊沙康唑相互作用引起的高钙血症 APL 病例。
一名 49 岁女性患者在出现全血细胞减少症时因广泛瘀斑和发热就诊，经检查后被诊断为 APL。开始使用泊沙康唑和 ATRA 后，她的血清钙水平开始升高（10.3 至 11.1mg/dl）。她的维生素 D 水平为 21.9ng/ml，PTH 为 17.8pg/ml，均在正常范围内。我们病例的药物相互作用概率评分计算为 6，表明可能发生不良反应。因此，高血清钙水平归因于 ATRA 和泊沙康唑之间的相互作用。
尽管文献中先前报道了 ATRA 与其他抗真菌药物联合使用时出现高钙血症，但这是首例报告 ATRA 与泊沙康唑联合使用时出现高钙血症的病例。
该病例强调了在与抑制细胞色素 P450 酶的药物联合使用时监测 ATRA 副作用的重要性。总之，泊沙康唑和 ATRA 的同时使用可能导致高钙血症，并且停用这些药物后血清钙水平恢复正常范围。
