Evaluation of the interaction of intravenous and oral voriconazole with oral cyclosporine in iranian HSCT patients

Abstract

Objective:Voriconazole as a triazole antifungal agent is widely used for prophylaxis or treatment of fungal infections in allogeneic hematopoietic stem cell transplantation (HSCT). It can increase blood concentrations of other medications including cyclosporine A (CsA) which are substrates for cytochrome P450 3A4. The aim of this study was to evaluate comparatively the interaction between oral/intravenous (IV) voriconazole and oral CsA.Methods:Twenty-nine recipients of allogeneic HSCT who had been already on a steady dose of CsA and were started on oral or IV voriconazole were evaluated in a prospective cohort study. Blood concentration of CsA was determined before and 5–8 days after voriconazole initiation. Plasma concentration of voriconazole was measured in steady state. The changes in blood concentration of CsA after administration of voriconazole were evaluated.Findings:The concentration/dose (C/D) ratio of CsA increased significantly (P < 0.001) after voriconazole initiation in both routes of administration (8.40%–174.10% increase in C/D ratio). The C/D ratio alteration of CsA did not differ significantly between oral and IV voriconazole group (P = 0.405). There was a significant correlation in all patients between plasma concentration of voriconazole and percentage of CsA C/D ratio increment (P = 0.046).Conclusion:There was a significant intrapatient variability in the magnitude of CsA blood concentration increment after voriconazole initiation. We also demonstrated that magnitude of drug interaction did not differ in IV and oral voriconazole administration. Furthermore, we found that the magnitude of drug interaction was correlated with plasma concentration of voriconazole.

Effects of Triazole Antifungal Agents on the Plasma Concentration and Dosage of Cyclosporin in Patients with Aplastic Anaemia

“…Tis is because it impacts whether it is necessary to preemptively reduce the dosage of CsA according to the instructions when coadministered with triazole antifungal drugs in patients with diferent diseases. Hamidreza et al [26] found that the mean C/D ratio of CsA increased 8.40%-174.10% when co-administered with VCZ in patients received HSCT. POSA increased the mean C/D ratio of CsA to a similar extent in patients with aplastic anaemia in current study (7.60%-184.00%).…”

“…Sanchez-Ortega et al [20] suggested that reducing the CsA dose may lead to a subtherapeutic CsA concentration, thus afecting the therapeutic efect. Hadjibabaie et al [26] suggested avoiding uniform reduction in all patients before voriconazole administration, and recommend frequent CsA blood concentration monitoring, once voriconazole antifungal therapy is initiated. In addition, a study also indicated that the dose adjustment of CsA inhibitors for initiating azoles should not be decided uniformly but should be determined individually by closely monitoring their blood concentrations [31].…”

Risk factors for early onset acute kidney injury after allogeneic haematopoietic stem cell transplantation and the role of drug–drug interactions

“…Masoumi et al found that starting voriconazole increased the ciclosporin blood level to administered dose ratio from 8.4% to 174.1%. It is noted that patient-based factors may play an important role in this wide range of occurrences 22. Posaconazole, another interacting drug, is shown to be an important cause of increased ciclosporin blood levels.…”