Hypercalcemia associated with interaction between all trans retinoic acid and fluconazole in an acute promyelocytic leukemia and acquired hypoparathyroidism case

Abstract

Introduction Acute promyelocytic leukemia (APL) is the most malignant form of acute myeloid leukemia (AML) with short survival without treatment. All trans retinoic acid (ATRA) is a vitamin A metabolite and plays an important role in the treatment of APL. Hypercalcemia is a rare side effect of ATRA. Case Report A 67-year-old female patient was investigated due to widespread bruising and pancytopenia. The patient was diagnosed with APL and remission was achieved by administering idarubicin together with ATRA in the induction treatment. The patient has hypocalcemia due to acquired hypoparathyroidism, and it was observed that the calcium level increased with the initiation of fluconazole 200 mg/day for antifungal prophylaxis together with ATRA in the consolidation treatment. It was observed that the calcium value reached 13 mg/dL by increasing the fluconazole to 400 mg/day treatment dose due to oral mucositis. Management and Outcome The development of hypercalcemia has been reported in previous case reports when ATRA is used together with voriconazole, fosfluconazole, itraconazole, and posaconazole, which inhibit cytochrome P450 enzymes. In this case, it is the first in the literature that a patient with hypocalcemia due to acquired hypoparathyroidism developed hypercalcemia after fluconazole and ATRA were used together. Discussion Since hypercalcemia may develop while azole drugs are administered during ATRA treatment, it is important to monitor calcium levels to prevent complications of hypercalcemia.