Integration of tacrolimus pharmacogenetics into medication therapy management in kidney transplant patients
DOI:
https://doi.org/10.33448/rsd-v10i10.18589Keywords:
Tacrolimus; Polymorphism, single nucleotide (SNP); Kidney transplantation; Pharmacogenomics; Pharmacogenetics; Cytochrome P-450 CYP3A Inducers; Medication therapy management; Precision medicine; Clinical pharmacy.Abstract
The pharmacogenetic analysis of tacrolimus and medication therapy management have already been analyzed in isolation as clinical strategies in renal transplant patients, and studies on the integration of these two practices are still scarce. The objective of this research was to integrate these tools in the care of kidney transplant patients. This is a retrospective observational study with 70 patients, 42 of whom were being treated by the medication therapy management service. We analyzed gender, age, time since the transplant, type of donor and drug-related problems. The allelic frequency of CYP3A5 (rs776746) was obtained by identifying the individuals regarding the presence of the functional *1 allele (expressors). There was a tacrolimus higher plasma concentration in expressors, but without change in the mean dose of this drug between groups. Regarding the frequency of drug-related problems, it was observed that 11 (27%) patients had none, 19 (47.5%) had only one, and 5 (12.5%), two or three. The integration of tacrolimus pharmacogenetics is a useful and complementary tool to the results obtained with the medication therapy management, as significant changes in the plasma concentration of this drug in expressors can signal to the multidisciplinary team a need for more attention in monitoring these patients, in order to avoid problems of effectiveness, safety and convenience. Furthermore, the identification of other health problems of the patient makes the medication therapy management necessary to ensure the use of medications appropriate, effective and safe.
References
Apha. (2021). Medication Therapy Management Services. American Pharmacists Association (Apha). http://www.pharmacist.com/medication-therapy-management-services.
Anutrakulchai, S., Pongskul, C., Kritmetapak, K., Limwattananon, C., & Vannaprasaht, S. (2019). Therapeutic concentration achievement and allograft survival comparing usage of conventional tacrolimus doses and CYP3A5 genotype‐guided doses in renal transplantation patients. British Journal of Clinical Pharmacology, 85(9), 1964-1973.
Auglienė, R., Dalinkevičienė, E., Kuzminskis, V., Jievaltas, M., Peleckaitė, L., Gryguc, A., & Bumblytė, I. A. (2017). Factors influencing renal graft survival: 7-Year experience of a single center. Medicina, 53(4), 224-232.
Barraclough, K. A., Isbel, N. M., Lee, K. J., Bergmann, T. K., Johnson, D. W., McWhinney, B. C., & Staatz, C. E. (2012). NR1I2 polymorphisms are related to tacrolimus dose-adjusted exposure and BK viremia in adult kidney transplantation. Transplantation, 94(10), 1025-1032.
Bautista, A. A., Álvarez, A. A., Urrea, E. M., Mondragón, G., Mendoza, S. A., Mendoza, R. P., & Ponce, D. V. (2018, March). Renal Transplantation in Second-Level Private Hospitals in the State of Mexico. In Transplantation proceedings (Vol. 50, No. 2, pp. 449-453). Elsevier.
Birdwell, K. A., Decker, B., Barbarino, J. M., Peterson, J. F., Stein, C. M., Sadee, W., & MacPhee, I. A. (2015). Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for CYP3A5 genotype and tacrolimus dosing. Clinical Pharmacology & Therapeutics, 98(1), 19-24.
Brasil. (2021). Ministério da Saúde (MS). Portaria SAES/SCTIE. nº 1, de 05 de janeiro de 2021.Aprova o Protocolo Clínico e Diretrizes Terapêuticas para Imunossupressão em Transplante Renal
Brown, J. T., MacDonald, D., Yapel, A., Luczak, T., Hanson, A., & Stenehjem, D. D. (2021). Integrating pharmacogenetic testing via medication therapy management in an outpatient family medicine clinic. Pharmacogenomics, 22(04), 203-212.
Brummel, A., & Carlson, A. M. (2016). Comprehensive medication management and medication adherence for chronic conditions. Journal of managed care & specialty pharmacy, 22(1), 56-62.
Brunet, M., Van Gelder, T., Åsberg, A., Haufroid, V., Hesselink, D. A., Langman, L., & Bergan, S. (2019). Therapeutic drug monitoring of tacrolimus-personalized therapy: second consensus report. Therapeutic drug monitoring, 41(3), 261-307.
Burns, A. (2008). Medication therapy management in pharmacy practice: core elements of an MTM service model (version 2.0). Journal of the American Pharmacists Association, 48(3), 341-353.
Campagne, O., Mager, D. E., & Tornatore, K. M. (2019). Population pharmacokinetics of tacrolimus in transplant recipients: what did we learn about sources of interindividual variabilities? The Journal of Clinical Pharmacology, 59(3), 309-325.
Chen, L., & Prasad, G. R. (2018). CYP3A5 polymorphisms in renal transplant recipients: influence on tacrolimus treatment. Pharmacogenomics and personalized medicine, 11, 23.
Chisholm-Burns, M. A., Spivey, C. A., Tolley, E. A., & Kaplan, E. K. (2016). Medication therapy management and adherence among US renal transplant recipients. Patient preference and adherence, 10, 703.
Cipolle RJ, Strand LM, Morley PC. Pharmaceutical care practice: the patient-centered approach to medication management. McGraw Hill Professional; Apr 22. 2012.
Correr, C. J., & Otuki, M. F. (2011). Método clínico de atenção farmacêutica. Revista Pan-Amazônica de Saúde. 1-11. https://edisciplinas.usp.br/pluginfile.php/380717/mod_folder/content/0/CORRER%20e%20OTUKI%2C%202011%20-%20M%C3%A9todo%20cl%C3%ADnico%20de%20Aten%C3%A7%C3%A3o%20Farmac%C3%AAutica.pdf?forcedownload=1.
Covert, K. L., Mardis, C. R., Fleming, J. N., Pilch, N. A., Meadows, H. B., Mardis, B. A., & Taber, D. J. (2017). Development of a predictive model for drug‐related problems in kidney transplant recipients. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 37(2), 159-169.
Farrell, B., Pottie, K., Thompson, W., Boghossian, T., Pizzola, L., Rashid, F. J., & Moayyedi, P. (2017). Deprescribing proton pump inhibitors: evidence-based clinical practice guideline. Canadian Family Physician, 63(5), 354-364.
Genvigir, F. D. V., Campos-Salazar, A. B., Felipe, C. R., Tedesco-Silva Jr, H., Medina-Pestana, J. O., Doi, S. D. Q., & Hirata, R. D. C. (2020). CYP3A5* 3 and CYP2C8* 3 variants influence exposure and clinical outcomes of tacrolimus-based therapy. Pharmacogenomics, 21(1), 7-21.
Ghoneim, M. A., Bakr, M. A., Refaie, A. F., Akl, A. I., Shokeir, A. A., Shehab El-Dein, A. B., & El-Baz, M. A. (2013). Factors affecting graft survival among patients receiving kidneys from live donors: a single-center experience. BioMed research international, 2013.
Haga, S. B., Allen LaPointe, N. M., & Moaddeb, J. (2015). Challenges to integrating pharmacogenetic testing into medication therapy management. Journal of managed care & specialty pharmacy, 21(4), 346-352.
Hicks, J. K., Aquilante, C. L., Dunnenberger, H. M., Gammal, R. S., Funk, R. S., Aitken, S. L., & Lee, J. C. (2019). Precision pharmacotherapy: integrating pharmacogenomics into clinical pharmacy practice. Journal of the American College of Clinical Pharmacy, 2(3), 303-313.
Htun, Y. Y., Swe, H. K., & Saw, T. M. (2018, May). CYP3A5* 3 genetic polymorphism and tacrolimus concentration in myanmar renal transplant patients. In Transplantation proceedings. 50(4), 1034-1040. Elsevier.
Jannot, A. S., Vuillemin, X., Etienne, I., Buchler, M., de Ligny, B. H., Choukroun, G., & Pallet, N. (2016). A lack of significant effect of POR* 28 allelic variant on tacrolimus exposure in kidney transplant recipients. Therapeutic drug monitoring, 38(2), 223-229.
Kagaya, H., Niioka, T., Saito, M., Inoue, T., Numakura, K., Yamamoto, R., & Miura, M. (2018). Prediction of tacrolimus exposure by CYP3A5 genotype and exposure of co-administered everolimus in Japanese renal transplant recipients. International journal of molecular sciences, 19(3), 882.
Katsakiori, P. F., Papapetrou, E. P., Sakellaropoulos, G. C., Goumenos, D. S., Nikiforidis, G. C., & Flordellis, C. S. (2010). Factors affecting the long-term response to tacrolimus in renal transplant patients: pharmacokinetic and pharmacogenetic approach. International journal of medical sciences, 7(2), 94.
Kravljaca, M., Perovic, V., Pravica, V., Brkovic, V., Milinkovic, M., Lausevic, M., & Naumovic, R. (2016). The importance of MDR1 gene polymorphisms for tacrolimus dosage. European Journal of Pharmaceutical Sciences, 83, 109-113.
Lamba, J., Hebert, J. M., Schuetz, E. G., Klein, T. E., & Altman, R. B. (2012). PharmGKB summary: very important pharmacogene information for CYP3A5. Pharmacogenetics and genomics, 22(7), 555.
Leite, R. F., Silva, A. C. M., Oliveira, P. C. D., Silva, L. M. G. D., Pestana, J. M. D. A., Schirmer, J., & Roza, B. D. A. (2018). Mensuração da adesão aos medicamentos imunossupressores em receptores de transplante renal. Acta Paulista de Enfermagem, 31, 489-496.
Liu, F., Ou, Y. M., Yu, A. R., Xiong, L., & Xin, H. W. (2017). Long-term influence of CYP3A5, CYP3A4, ABCB1, and NR1I2 polymorphisms on tacrolimus concentration in Chinese renal transplant recipients. Genetic testing and molecular biomarkers, 21(11), 663-673.
Liu, J. Y., You, R. X., Guo, M., Zeng, L., Zhou, P., Zhu, L., & Liu, D. (2016). Tacrolimus versus cyclosporine as primary immunosuppressant after renal transplantation: a meta-analysis and economics evaluation. American journal of therapeutics, 23(3), e810-e824.
Murphy-Menezes, M. (2015). Role of the pharmacist in medication therapy management services in patients with osteoporosis. Clinical therapeutics, 37(7), 1573-1586.
O’Connor, S. K., Ferreri, S. P., Michaels, N. M., Chater, R. W., Viera, A. J., Faruki, H., & Roederer, M. (2012). Making pharmacogenetic testing a reality in a community pharmacy. Journal of the American Pharmacists Association, 52(6), e259-e265.
Pallet, N., Etienne, I., Buchler, M., Bailly, E., Hurault de Ligny, B., Choukroun, G., & Thervet, E. (2016). Long‐Term Clinical Impact of Adaptation of Initial Tacrolimus Dosing to CYP 3A5 Genotype. American Journal of Transplantation, 16(9), 2670-2675.
Peloso, L. J. (2014). A concentração sérica de tacrolimo após a ingestão de omeprazol: um estudo piloto. Dissertação de mestrado.
R Core Team (2020). R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna. Austria. URL https://www.R-project.org/.
Ramalho de Oliveira, D. (2011). Atenção Farmacêutica: da filosofia ao gerenciamento da terapia medicamentosa. São Paulo: RCN.
Roederer, M. W., Kuo, G. M., Kisor, D. F., Frye, R. F., Hoffman, J. M., Jenkins, J., & Weitzel, K. W. (2017). Pharmacogenomics competencies in pharmacy practice: a blueprint for change. Journal of the American Pharmacists Association, 57(1), 120-125.
Rojas, L., Neumann, I., Herrero, M. J., Boso, V., Reig, J., Poveda, J. L., & Aliño, S. F. (2015). Effect of CYP3A5* 3 on kidney transplant recipients treated with tacrolimus: a systematic review and meta-analysis of observational studies. The pharmacogenomics journal, 15(1), 38-48.
Santoro, A., Felipe, C. R., Tedesco-Silva, H., Medina-Pestana, J. O., Struchiner, C. J., Ojopi, E. B., & Suarez-Kurtz, G. (2011). Pharmacogenetics of calcineurin inhibitors in Brazilian renal transplant patients. Pharmacogenomics, 12(9), 1293-1303.
Severova-Andreevska, G., Danilovska, I., Sikole, A., Popov, Z., & Ivanovski, N. (2019). Hypertension after kidney transplantation: clinical significance and therapeutical aspects. Open access Macedonian journal of medical sciences, 7(7), 1241.
Shuker, N., Bouamar, R., van Schaik, R. H., Clahsen‐van Groningen, M. C., Damman, J., Baan, C. C., & Hesselink, D. A. (2016). A randomized controlled trial comparing the efficacy of Cyp3a5 genotype‐based with body‐weight‐based tacrolimus dosing after living donor kidney transplantation. American Journal of Transplantation, 16(7), 2085-2096.
Stefanović, N. Z., Cvetković, T. P., Veličković-Radovanović, R. M., Jevtović-Stoimenov, T. M., Vlahović, P. M., Stojanović, I. R., & Pavlović, D. D. (2015). Pharmacogenetics may influence tacrolimus daily dose, but not urinary tubular damage markers in the long-term period after renal transplantation. Journal of medical biochemistry, 34(4), 422-430.
Stratta, P., Quaglia, M., Cena, T., Antoniotti, R., Fenoglio, R., Menegotto, A., & Magnani, C. (2012). The interactions of age, sex, body mass index, genetics, and steroid weight-based doses on tacrolimus dosing requirement after adult kidney transplantation. European journal of clinical pharmacology, 68(5), 671-680.
Suarez-Kurtz, G., & Parra, E. J. (2018). Population diversity in pharmacogenetics: a Latin American perspective. Advances in Pharmacology, 83, 133-154.
Suarez-Kurtz, G., Med, D., Pena, S. D. J., Struchiner, C. J., & Hutz, M. H. (2012). Pharmacogenomic diversity among Brazilians: influence of ancestry, self-reported color, and geographical origin. Frontiers in pharmacology, 3, 191.
Suarez-Kurtz, G., Vargens, D. D., Santoro, A. B., Hutz, M. H., de Moraes, M. E., Pena, S. D., & Struchiner, C. J. (2014). Global pharmacogenomics: distribution of CYP3A5 polymorphisms and phenotypes in the Brazilian population. PLoS One, 9(1), e83472.
Tang, J., Xu, J., Zhang, Y. L., Liu, R., Liu, M. Z., Hu, Y. F., & Zhou, G. (2019). Incorporation of Gene‐Environment Interaction Terms Improved the Predictive Accuracy of Tacrolimus Stable Dose Algorithms in Chinese Adult Renal Transplant Recipients. The Journal of Clinical Pharmacology, 59(6), 890-899.
Tantisattamo, E., Molnar, M. Z., Ho, B. T., Reddy, U. G., Dafoe, D. C., Ichii, H., & Amin, A. (2020). Approach and management of hypertension after kidney transplantation. Frontiers in Medicine, 7, 229.
Tavira, B., Garciá, E. C., Díaz-Corte, C., Ortega, F., Arias, M., Torres, A., & Alvarezca, V. (2011). Pharmacogenetics of tacrolimus after renal transplantation: analysis of polymorphisms in genes encoding 16 drug metabolizing enzymes. Clinical Chemistry and Laboratory Medicine (CCLM), 49(5), 825-833.
Thervet, E., Loriot, M. A., Barbier, S., Buchler, M., Ficheux, M., Choukroun, G., & Legendre, C. (2010). Optimization of initial tacrolimus dose using pharmacogenetic testing. Clinical Pharmacology & Therapeutics, 87(6), 721-726.
Tsuchiya, N., Satoh, S., Tada, H., Li, Z., Ohyama, C., Sato, K., & Kato, T. (2004). Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation, 78(8), 1182-1187.
Vankova, B., Mala-Ladova, K., Kubena, A. A., Maly, J., & Sulkova, S. D. (2018). Immunosuppressive therapy related adherence, beliefs and self-management in kidney transplant outpatients. Patient preference and adherence, 12, 2605.
Viswanathan, M., Kahwati, L. C., Golin, C. E., Blalock, S. J., Coker-Schwimmer, E., Posey, R., & Lohr, K. N. (2015). Medication therapy management interventions in outpatient settings: a systematic review and meta-analysis. JAMA internal medicine, 175(1), 76-87.
Wang, Y. T., Merl, M. Y., Yang, J., Zhu, Z. X., & Li, G. H. (2020). Opportunities for pharmacists to integrate pharmacogenomics into clinical practice. The pharmacogenomics journal, 20(2), 169-178.
Weir, M. R., Burgess, E. D., Cooper, J. E., Fenves, A. Z., Goldsmith, D., McKay, D., & Taler, S. J. (2015). Assessment and management of hypertension in transplant patients. Journal of the American Society of Nephrology, 26(6), 1248-1260.
Woillard, J. B., Chouchana, L., Picard, N., Loriot, M. A., & of Pharmacogenetics, F. N. (2017). Pharmacogenetics of immunosuppressants: State of the art and clinical implementation–recommendations from the French National Network of Pharmacogenetics (RNPGx). Therapies, 72(2), 285-299.
Xu, X. F., Feng, Y. T., Tian, Y. F., & Wang, H. Y. (2018). Pharmaceutical care in kidney transplant recipients: behavioral and physiologic outcomes at 12 months. In Transplantation proceedings (Vol. 50, No. 8, pp. 2451-2456). Elsevier.
Yang, H., Li, L., Hu, X., Wang, W., Yang, X., Liu, H., & Liu, L. (2019). Impact of pharmacist‐led post‐transplant medication management for kidney transplant recipients: A retrospective pre‐and post‐intervention study. Journal of clinical pharmacy and therapeutics, 44(4), 603-610.
Yang, Y., West-Strum, D. (2013). Compreendendo a Farmacoepidemiologia. AMGH.
Yaowakulpatana, K., Vadcharavivad, S., Ingsathit, A., Areepium, N., Kantachuvesiri, S., Phakdeekitcharoen, B., & Kitiyakara, C. (2016). Impact of CYP3A5 polymorphism on trough concentrations and outcomes of tacrolimus minimization during the early period after kidney transplantation. European journal of clinical pharmacology, 72(3), 277-283.
Yau, W. P., Loh, C. W. T., & Vathsala, A. (2019). Conversion from twice-daily Prograf® to once-daily Advagraf® in multi-ethnic Asian adult renal transplant recipients with or without concomitant use of diltiazem: impact of CYP3A5 and MDR1 genetic polymorphisms on tacrolimus exposure. European journal of drug metabolism and pharmacokinetics, 44(4), 481-492.
Yu, M., Liu, M., Zhang, W., & Ming, Y. (2018). Pharmacokinetics, pharmacodynamics and pharmacogenetics of tacrolimus in kidney transplantation. Current drug metabolism, 19(6), 513-522.
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