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Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation

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Abstract

Purpose

This study aimed to investigate the interactions between posaconazole (POS) and intravenously/orally administered cyclosporine A (CsA) in allogeneic hematopoietic stem cell transplant (HSCT) recipients.

Methods

We included 118 allogeneic HSCT patients who received CsA and POS simultaneously between January 2017 and June 2020 in this study. The ratio of CsA blood concentration (ng/mL) to dosage (mg/day) (C/D) before and after POS initiation was compared.

Results

After the initiation of POS, the level of CsA increased 1 to 2 times in 66% (78/118) of patients compared to those without POS. However, the CsA C/D ratio increased by more than threefold in 6% (7/118) of patients after POS initiation, with an increase of more than fourfold in two patients. The median C/D ratio of CsA increased from 0.89 to 1.23 (P < 0.001) and 0.78 to 1.22 (P < 0.001) after POS initiation when CsA was administered intravenously and orally, respectively. In patients who received POS at the time of transition from intravenous to oral CsA, the value increased from 1.01 to 1.38 (P = 0.001). The route of administration had no significant effect on the change in the CsA C/D ratio (P = 0.615). Additionally, we observed the time required for the C/D ratio to reach a plateau after POS initiation was similar on days 13, 8, and 15 under various scenarios.

Conclusion

POS treatment increased blood CsA levels. A large variability was found in the fold-change in the CsA C/D ratio. Therefore, CsA doses should be adjusted by closely monitoring the blood levels of CsA after POS initiation.

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Data availability

All data included in this study are available from corresponding author upon request.

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Acknowledgements

The authors thank all patients who contributed to this work.

Funding

This research received no external funding.

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Authors and Affiliations

  1. Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China

    Li-E Zhu, Hui-Ping Huang, Yi-Peng Cai, Yan Wang, Bao-Hua Xu, Mao-Bai Liu & Xue-Mei Wu

  2. School of Pharmacy, Fujian Medical University, Fuzhou, 350122, Fujian, China

    Li-E Zhu, Hui-Ping Huang, Bao-Hua Xu, Mao-Bai Liu & Xue-Mei Wu

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  1. Li-E Zhu
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Contributions

All authors contributed to the initial discussion. ZLE, HHP, CYP, WY and XBH designed the study, collected data, analyzed and interpreted data. ZLE wrote the first draft. LMB and WXM supervised the study and revised the manuscript.

Corresponding author

Correspondence to Xue-Mei Wu.

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Ethics approval

The study was approved by an independent ethics committee at Fujian Medical University Union Hospital and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice. The requirement for informed consent was waived because only retrospective data were collected.

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Zhu, LE., Huang, HP., Cai, YP. et al. Effect of posaconazole on the concentration of intravenous and oral cyclosporine in patients undergoing hematopoietic stem cell transplantation. Eur J Clin Pharmacol 78, 1677–1685 (2022). https://doi.org/10.1007/s00228-022-03378-z

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