Rationale: All-trans retinoic acid (ATRA) and voriconazole (VRZ) are pivotal drugs for the treatment of acute promyelocytic leukemia (APL) and invasive fungal infections, respectively. When ATRA is co-administered with VRZ, clinically significant drug interactions may occur due to alterations in drug metabolism and clearance. Patient concerns: We report a case of hypercalcemia caused by the interaction between ATRA and VRZ in a child with APL. Diagnoses and interventions: A 14-year-old boy received arsenictrioxide (ATO) for APL and VRZ for invasive fungal infections, followed by planned maintenance therapy with ATRA monotherapy and combination of ATRA and ATO. He experienced no adverse reactions during the concurrent use of ATO and VRZ, while on the 12th day of combined ATRA and VRZ administration, his blood calcium levels significantly increased, accompanied by a series of symptoms. Following the discontinuation of VRZ and continuation of ATRA monotherapy, and subsequent maintenance chemotherapy with ATRA and ATO, his blood calcium levels decreased and remained within the normal range. Outcomes: We reviewed the published literature and excluded primary hyperparathyroidism or ectopic parathyroid hormone secretion as the cause of hypercalcemia in the child. He did not use other cytochrome inhibitors that may affect ATRA metabolism other than VRZ. Multiple measurements of VRZ trough concentrations ranged from 1.2 to 3 μg/mL. According to the Drug Interaction Probability Scale (5 points) and Naranjo Probability Scale (4 points), the drug interaction between VRZ and ATRA is probable. The hypercalcemia and other clinical manifestations may be caused by the inhibition of ATRA metabolism by VRZ. Lessons: During clinical use of ATRA, it is necessary to closely monitor the adverse drug interactions such as hypercalcemia and limit the use of drugs that may affect cytochrome P450 enzyme such as VRZ.

Xanthii fructus (XF), a traditional Chinese medicine, is commonly used for anti-inflammatory and analgesic purposes; however, its hepatotoxicity limits its use to some extent and the underlying mechanisms remain unclear. The present study aimed to explore the key targets and molecular pathways of XF-induced liver injury through an integrated network toxicology and molecular docking approach. Potential hepatotoxic components of XF were screened using the TCMSP and comparative toxicogenomics database databases. Targets associated with these components and liver injury were identified via SwissTargetPrediction, GeneCards, and online Mendelian inheritance in man. Protein–protein interaction networks were constructed using STRING and analyzed with Cytoscape. The Metascape platform was used for gene ontology/Kyoto encyclopedia of genes and genomes enrichment analysis, and molecular docking was performed to validate the interactions between the key components and targets. Five hepatotoxic active ingredients were finally screened, involving 74 hepatotoxic targets, and significantly enriched pathways were uncovered through rigorous Kyoto encyclopedia of genes and genomes analysis. The most prominent was pathways in cancer [ P <.001; false discovery rate (q-value) <0.001], followed by Hepatitis B [ P <.001; false discovery rate (q-value) <0.001]. Among them, TP53, HSP90AA1, JUN, and EP300 served as core targets. Molecular docking confirmed the strong binding affinity between the key targets and hepatotoxic components (binding energy: −6.83 to −9.28 kcal/mol). This study provides a preliminary framework for XF-induced hepatotoxicity, highlighting multi-component, multi-target interactions. Mechanistic predictions require preclinical validation. Future work should validate these findings experimentally and explore detoxification strategies to enable safer clinical use of XF.