Authors

• Nives Kerner — Zadar General Hospital, Zadar, Croatia — ORCID: 0009-0006-7303-5644
• Jure Samardžić — University Hospital Centre Zagreb, Zagreb, Croatia — ORCID: 0000-0002-9346-6402
• Nada Božina — University of Zagreb, Zagreb, Croatia — ORCID: 0000-0001-6016-1699

Keywords

heart transplantation, tacrolimus, pharmacogenetics

DOI

Full Text

**Introduction:** Tacrolimus is a cornerstone of modern immunosuppressive regimen after heart transplantation. Optimizing it’s use is crucial to increase effectiveness and reduce potential harm. (1-3) This paper aimed to present key insights into the pharmacogenetic profile of crucial cytochrome P450 (CYP) enzymes and ABC transporters involved in tacrolimus metabolism. **Materials and Methods:** This study involved search and review of relevant literature in PubMed and PharmGKB database using keywords: heart transplantation, immunosuppressive therapy, tacrolimus, pharmacogenetics, pharmacogenomics, CYP3A4, CYP3A5, polymorphism and pharmacoeconomics. **Results:** A systematic review of the literature established links between gene polymorphisms and tacrolimus metabolism. Whether therapeutic drug monitoring could be replaced by routine pharmacogenetic testing to adjust tacrolimus dosing more efficiently is still debated. Currently, the metabolizer phenotype CYP3A5 *1/*1 or *1/*3 is the only one with official guidelines, indicating these patients may need a 1.5 to 2-fold dose increase to achieve therapeutic levels. These guidelines are published by Clinical Pharmacogenetics Implementation Consortium (CPIC). Other referent scientific societies have similar guidelines. Among Caucasians, 3-15% are CYP3A5 expressors (*1 carriers). **Conclusion:** Further research is required to assess the cost-effectiveness of routine pharmacogenetic testing in clinical practice, considering its potential to prevent side effects and drug inefficacy. While pharmacogenetic testing provides valuable dosing insights, it should complement other clinical and laboratory tools in a multidisciplinary approach that includes the clinical pharmacist as part of the team.

Literature

1. Brunet M, van Gelder T, Åsberg A, Haufroid V, Hesselink DA, Langman L, et al. Therapeutic Drug Monitoring of Tacrolimus-Personalized Therapy: Second Consensus Report. Ther Drug Monit. 2019 June;41(3):261–307. https://doi.org/10.1097/FTD.0000000000000640
2. Relling MV, Klein TE. CPIC: Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network. Clin Pharmacol Ther. 2011 March;89(3):464–7. https://doi.org/10.1038/clpt.2010.279
3. Pharm GKB. Tacrolimus. Prescribing info. Available at:. https://www.pharmgkb.org/chemical/PA451578/prescribingInfo