Case report: dose-dependent interaction between dexamethasone and voriconazole in severely ill patients with non-Hodgkin’s lymphoma being treated for invasive pulmonary aspergillosis

• Published in: Frontiers in pharmacology Vol. 15; p. 1403966
• Main Authors: Huang, Jingjing, Chen, Yang, Zhong, Ming, Tan, Ruoming
• Format: Journal Article
• Language: English
• Published: Frontiers Media S.A 27.06.2024
• Subjects: aspergillosis; case report; dexamethasone dose; drug interaction; Pharmacology; therapeutic drug monitoring; voriconazole trough concentration
• ISSN: 1663-9812; 1663-9812
• DOI: 10.3389/fphar.2024.1403966

Background Voriconazole is primarily metabolized by CYP2C19 and CYP3A4. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted voriconazole concentrations. Case summary In this case report, we describe the case of a 64-year-old man who was treated for non-Hodgkin’s lymphoma with continuous glucocorticoids co-administrated with voriconazole against invasive pulmonary aspergillosis. A decrease in trough concentration (C min ) of voriconazole was observed and related with co-administration of dexamethasone in the patient carrying the CYP2C19 *1*2 genotype: voriconazole C min /dose ratios of 0.018 (0.1 mg L −1 /5.7 mg kg −1  day −1 ), 0.18 (1 mg L −1 /5.7 mg kg −1  day −1 ), and 0.23 (2 mg L −1 /8.6 mg kg −1  day −1 ) at dexamethasone doses of 20, 12.5, and 2.5 mg, respectively. Sub-therapeutic voriconazole C min was associated with high- and moderate-dose dexamethasone (20 and 12.5 mg), leading to failure of antifungal treatment. Conclusion The extent of voriconazole–dexamethasone interaction was determined by the dose of dexamethasone and associated with the CYP2C19 *1*2 genotype. Therapeutic drug monitoring of voriconazole is necessary to avoid clinically relevant interactions for optimal antifungal therapy.