Immunosuppressive serum levels in allogeneic hematopoietic stem cell transplantation: pharmaceutical care contribution
Main Article Content
Medication Adherence, Bone Marrow Transplantation, Pharmaceutical Services, Professional Practice, Non-Randomized Controlled Trials as Topic, Brazil
Background: Cyclosporine and tacrolimus are limited by a narrow therapeutic window. Maintaining immunosuppressive drugs at desired levels may be difficult. Pharmaceutical care emerges as a philosophy of practice that enhances medication use and leads to a better control of serum concentration.
Objective: This study aims to evaluate the impact of pharmaceutical care in the maintaining of proper serum levels of immunosuppressive medications in patients who have undergone allo-HSCT.
Methods: The study had a quasi-experimental design that included a comparison group. The service model used was pharmacotherapy follow-up, according to an adaptation of the Dader method. The pharmacist consultation was carried out at a day-hospital or at the outpatient hematology clinic as needed. The intervention group consisted of 22 patients seen by a clinical pharmacist. The control group consisted of 44 patients that received standard care. This study aims to evaluate the impact of pharmaceutical care on keeping patient serum levels of cyclosporine and tacrolimus within the desired range.
Results: Control group displayed 65% of the proper serum levels of immunosuppressive agents. While In intervention group, the figure was 82% (p = 0.004).
Conclusion: The role of the pharmacist in the multidisciplinary team may contribute to a greater success in attaining the patients’ therapeutic targets with regard to the use of immunosuppressant.
2. Ram R, Storer B, Mielcarek M, Sandmaier BM, Maloney DG, Martin PJ, Flowers ME, Chua BK, Rotta M, Storb R. Association between calcineurin inhibitor blood concentrations and outcomes after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):414-422. doi: 10.1016/j.bbmt.2011.08.016
3. Rogosheske JR, Fargen AD, DeFor TE, Warlick E, Arora M, Blazar BR, Weisdorf DJ, Brunstein CG. Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival. Bone Marrow Transplant. 2014 Jan;49(1):122-125. doi: 10.1038/bmt.2013.139
4. Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol. 2012;158(1):30-45. doi: 10.1111/j.1365-2141.2012.09129.x
5. Mohammadpour N, Elyasi S, Vahdati N, Mohammadpour AH, Shamsara J. A review on therapeutic drug monitoring of immunosuppressant drugs. Iran J Basic Med Sci. 2011;14(6):485-498.
6. Lesche D, Sigurdardottir V, Setoud R, Oberhänsli M, Carrel T, Fiedler GM, Largiadèr CR, Mohacsi P, Sistonen J. CYP3A5*3 and POR*28 genetic variants influence the required dose of tacrolimus in heart transplant recipients. Ther Drug Monit. 2014;36(6):710-715. doi: 10.1097/FTD.0000000000000080
7. Song J, Kim MG, Choi B, Han NY, Yun HY, Yoon JH, Oh JM. CYP3A5 polymorphism effect on cyclosporine pharmacokinetics in living donor renal transplant recipients: analysis by population pharmacokinetics. Ann Pharmacother. 2012;46(9):1141-1151. doi: 10.1345/aph.1R004
8. Mori T, Kato J, Yamane A, Sakurai M, Kohashi S, Kikuchi T, Ono Y, Okamoto S. Drug interaction between voriconazole and tacrolimus and its association with the bioavailability of oral voriconazole in recipients of allogeneic hematopoietic stem cell transplantation. Int J Hematol. 2012;95(5):564-569. doi: 10.1007/s12185-012-1057-2
9. Leather H, Boyette RM, Tian L, Wingard JR. Pharmacokinetic evaluation of the drug interaction between intravenous itraconazole and intravenous tacrolimus or intravenous cyclosporin A in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant. 2006 Mar;12(3):325-334.
10. Sumi M, Konishi H, Ikuno Y, Hoshino N, Minouchi T, Yamaji A. Change in blood tacrolimus concentration by fluctuation of renal function in a bone marrow transplant patient. Eur J Drug Metab Pharmacokinet. 2009;34(3-4):201-204.
11. Dew M, DiMartini A, Dabbs A, Myaskovsky L, Steel J, Unruh M, Switzer GE, Zomak R, Kormos RL, Greenhouse JB. Rates and risk factors for nonadherence to the medical regimen after adult solid organ transplantation. Transplantation. 2007;83(7):858-873.
12. Griva K, Davenport A, Harrison M, Newman SP. Non-adherence to immunosuppressive medications in kidney transplantation: intent vs. forgetfulness and clinical markers of medication intake. Ann Behav Med. 2012;44(1):85-93. doi: 10.1007/s12160-012-9359-4
13. Chisholm MA, Mulloyb L, Jagadeesanb M, DiPiro J. Impact of clinical pharmacy services on renal transplant patients’ compliance with immunosuppressive medications. Clin Transplant. 2001;15(5):330-336.
14. Mishima K, Makino K, Shimada M, Suehiro T, Oishi R. Roles of pharmacist as a member of the liver transplant team in controlling tacrolimus whole blood concentrations and monitoring adverse drug events such as convulsion. Jpn J Pharm Health Care Sci. 2002;28:393-400. doi: 10.5649/jjphcs.28.393
15. Klein A, Otto G, Kramer I. Impact of a pharmaceutical care Program on liver transplant patients’ compliance with immunosuppressive medication: a prospective, randomized, controlled trial using electronic monitoring. Transplantation. 2009;87(6):839-847. doi: 10.1097/TP.0b013e318199d122
16. Musgravea CR, Pilch NA, Taber DJ, Meadows HB, McGillicuddy JW, Chavin KD, Baliga PK.. Improving transplant patient safety through pharmacist discharge medication reconciliation. Am J Transplant. 2013;13(3):796-801. doi: 10.1111/ajt.12070
17. Castro MS, Fuchs FD, Santos MC, Corrêa PM, Gus M, Moreira LB, Ferreira MB. Pharmaceutical care program for patients with uncontrolled hypertension. Am J Hypertens. 2006;19(5):528-533.
18. Lalić J, Veličković-Radovanović R, Mitić B, Paunović G, Cvetković T. Immunosuppressive medication adherence in kidney transplant patients. Med Princ Pract. 2014;23(4):351-356. doi: 10.1159/000362792
19. Silla L, Fischer GB, Paz A, Daudt LE, Mitto I, Katz B, da Graça Grossini M, Bittencourt HN, Jochims A, Fogliatto L, Bittar CM, Friedrisch JR, Bittencourt RI. Patient socioeconomic status as a prognostic factor for allo-SCT. Bone Marrow Transplant. 2009;43(7):571-577. doi: 10.1038/bmt.2008.358