造血幹細胞移植病人藥物交互作用處置－臨床資料庫與實證醫學運用的差異

Application of Evidence-Based Medicine in a Patient with Hematopoietic Stem Cell Transplantion

10.3966/168395442016061601003

董侑淳(Yu-Chun Tung)；劉文雄(Wen-Shyong Liou)

造血幹細胞移植 ； 藥物交互作用 ； voriconazole ； cyclosporine ； hematopoietic stem cell transplantation ； drug interaction ； voriconazole ； cyclosporine

腫瘤護理雜誌

16卷1期（2016 / 06 / 01）

15 - 24

繁體中文

隨著幹細胞資料庫建立及移植技術進步，接受幹細胞移植的病人持續增加，由於此類病人用藥複雜，照顧此類病人需具備藥物血中濃度監測及藥物交互作用處理的臨床能力。本文報告一位58歲男性化學治療期間曾發生肺部麴菌感染，持續使用voriconazole治療；之後因進行幹細胞移植，使用cyclosporine預防排斥反應。Micromedex與Lexicomp Interactions兩種藥學資料庫描述voriconazole會造成cyclosporine血中濃度明顯上升，本個案依資料庫建議降低cyclosporine一半劑量，卻得不到適當的治療效果。為釐清資料庫描述與臨床實例間差異造成的因素，以實證醫學文獻檢索策略進行文獻評讀後，調整藥學資料庫之建議，總結四項cyclosporine劑量調整與血中濃度監測之方法，做為醫療團隊日後照顧此類病人的依據。

As the number of donors in the bone marrow registry increases and the technology of stem cell transplantation advances, the number of patients for stem cell transplantation is continuously increasing. During the treatment, it is necessary to have concomitant use of calcinueurin inhibitors and triazoles in most cases. The staffs in transplant team should have the clinical capability to manage the therapeutic drug monitoring and drug interaction. This patient is a 58-year-old man who was diagnosed with acute myeloid leukemia. During the chemotherapy, he suffered from pulmonary aspergillosis and received voriconazole. Upon complete remission, he was admitted for the scheduled allogeneic hematopoietic stem cell transplantation. We reviewed the Micromedex and Lexicomp Interactions before initiating cyclosporine (CsA) therapy to prevent graft rejection and graft-versus-host disease. It's recommended that clinicians should reduce the CsA dose to one-half of the standard dose to prevent voriconazole-CsA drug interaction and monitor the CsA blood levels frequently. However, the expected treatment response wasn't achieved by the CsA trough levels. To ensure the drug efficacy and patient safety, we then conducted series of literature review with the evidence-based medicine approach and established four CsA dose adjustment models with related monitoring method. We also found more than 10 similar patients who had good outcome after implementing the dose adjustment model.

1. Cordonnier, C.,Rovira, M.,Maertens, J.,Olavarria, E.,Faucher, C.,Bilger, K.,Einsele, H.(2010).Voriconazole for secondary prophylaxis of invasive fungal infections in allogeneic stem cell transplant recipients: results of the VOSIFI study.Haematologica,95(10),1762-1768.
2. Kikuchi, T.,Mori, T.,Yamane, A.,Kato, J.,Kohashi, S.,Okamoto, S.(2012).Variable magnitude of drug interaction between oral voriconazole and cyclosporine A in recipients of allogeneic hematopoietic stem cell transplantation.Clinical Transplantation,26(5),E544-E548.
3. Kimura, S.,Oshima, K.,Okuda, S.,Sato, K.,Sato, M.,Terasako, K.,Kanda, Y.(2010).Pharmacokinetics of CsA during the switch from continuous intravenous infusion to oral administration after allogeneic hematopoietic stem cell transplantation.Bone Marrow Transplantation,45(6),1088-1094.
4. Mori, T.,Aisa, Y.,Kato, J.,Nakamura, Y.,Ikeda, Y.,Okamoto, S.(2009).Drug interaction between voriconazole and calcineurin inhibitors in allogeneic hematopoietic stem cell transplant recipients.Bone Marrow Transplantation,44(6),371-374.
5. Noreddin, Ayman(ed.)(2012).Optimal Pharmacokinetics of Cyclosporine and Tacrolimus Based Relationship Among AUC.
6. Romero, A. J.,Le Pogamp, P.,Nilsson, L. G.,Wood, N.(2002).Effect of voriconazole on the pharmacokinetics of cyclosporine in renal transplant patients.Clinical Pharmacology and Therapeutics,71(4),226-234.
7. Saad, A. H.,DePestel, D. D.,Carver, P. L.(2006).Factors influencing the magnitude and clinical significance of drug interactions between azole antifungals and select immunosuppressants.Pharmacotherapy,26(12),1730-1744.
8. Thorner, A. R.(ed.)(2015).Treatment and prevention of invasive aspergillosis.In Waltham, MA:UpToDate.
9. Voriconazole, cyclosporine(2014).In: Lexi-Comp OnlineTM, Pediatric Lexi-Drugs OnlineTM.Hudson (OH):Lexi-Comp, Inc..
10. Voriconazole, cyclosporine (2014). In: DRUGDEX® System (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ (cited: 09/06/2014).
11. Yang, T.,Wu, X. M.,Qiu, H. Q.,Fu, D. H.,Hu, J. D.,Li, J.,Chen, Z. Z.(2013).Adverse drug interactions as a high-risk factor for lethal post-transplant complications in Chinese population.Clinical Transplantion,27(2),255-260.