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Adverse effects of mycophenolic acid in renal transplant recipients: gender differences

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Abstract

Background Mycophenolic acid is widely used immunosuppressive drug, associated with adverse effects which increase patient morbidity and decrease medication adherence. Objective To evaluate the adverse effects in renal transplant recipients under mycophenolate treatment with respect to gender. Setting University Clinical Centre of Nis, Clinic of Nephrology, Serbia. Method This research included 96 renal transplant recipients, who received immunosuppressive regimen, based on tacrolimus or cyclosporin A, prednisone and mycophenolic acid. The high-performance liquid chromatography method combined with protein precipitation was used for the analysis of mycophelate concentration in human plasma. Drug concentration and dose-adjusted concentration were determined with respect to the patients’ gender. An adverse effect scoring system developed by nephrologists within the University of Buffalo Nephrology/Transplant Program was used to monitor adverse effects of therapy. Main outcome measure Individual and scores of adverse effects in relation to the dosing regimen and gender. Results Results showed statistically lower dose and concentrations in men compared to the women in our investigation group. Also, female patients demonstrated higher mean scores (cumulative and subscores) within the same dosing regimens of mycophenolic acid. The gastrointestinal score was significantly higher in women who received a dose greater than 720 mg compared to men (0.20 ± 0.12 vs 0.12 ± 0.12). Women demonstrated higher individual adverse effects such as diarrhea and skin changes (41.7 vs 17.0; p = 0.038 and 62.5 vs 30.2; p = 0.037, respectively). Conclusions The results of our research showed that recipients’ gender may play an important role in pharmacokinetic profile of mycophenolic acid, suggesting that women had higher concentration of mycophenolic acid and more serious side effects.

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Acknowledgements

The authors would like to thank Dr. Rocco Venuto, who gave us the support to apply the immunosuppressive adverse effects scoring system to our patients.

Funding

This study was supported by a grant from the Ministry of Education, Science and Technological Development of the Republic of Serbia—Project Nos. 41018 and 172044.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Medicine, University of Nis, Bulevar dr Zorana Djindjica 81, Nis, 18000, Serbia

    Ana Spasić, Aleksandra Catić-Đorđević, Radmila Veličković-Radovanović, Nikola Stefanović & Predrag Džodić

  2. Clinic of Nephrology, Clinical Centre Nis, Nis, Serbia

    Radmila Veličković-Radovanović & Tatjana Cvetković

  3. Institute of Biochemistry, Faculty of Medicine, University of Nis, Nis, Serbia

    Tatjana Cvetković

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  1. Ana Spasić
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  2. Aleksandra Catić-Đorđević
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  4. Nikola Stefanović
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  6. Tatjana Cvetković
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Correspondence to Ana Spasić.

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Spasić, A., Catić-Đorđević, A., Veličković-Radovanović, R. et al. Adverse effects of mycophenolic acid in renal transplant recipients: gender differences. Int J Clin Pharm 41, 776–784 (2019). https://doi.org/10.1007/s11096-019-00837-z

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