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KMID : 0869620230400030280
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Journal of Korean Society of Hospital Pharmacists
2023 Volume.40 No. 3 p.280 ~ p.291
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Evaluation of Tacrolimus Dosage during Co-administration of Posaconazole Enteric-coated Tablet in Allogenic Hematopoietic Stem Cell Transplantation
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Cho Ye-Jin
Lee Hyeon-Jin
Hong Sang-Hee
Koh Won-Kyung
Ahn Seo-Hyun
Woo Ji-Yun
Ahn Hye-Lim
Kwon Eyn-Young
Kang Jin-Suk
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Abstract
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Background : In allogenic hematopoietic stem-cell transplantation (HSCT), antifungal prophylaxis such as posaconazole is recommended to prevent invasive aspergillosis. However, blood concentration of tacrolimus is increased after taking it with posaconazole. The Ministry of Food and Drug Safety recommends the reduction of tacrolimus dose by one-third when receiving it with posaconzole. It was based on the study of posaconazole oral suspension. Thus, we evaluated the adequacy of tacrolimus dose adjustment when receiving it with posaconazole enteric-coated tablets in allogenic HSCT.
Methods : From January 2020 to December 2021, a single-center and retrospective study was conducted on patients who received tacrolimus and posaconazole enteric-coated tablets together for more than 5 days after allogenic HSCT. We investigated the mean blood concentration of tacrolimus before and after combination with posaconazole. Patients were divided into two groups: those with decreased tacrolimus dose by less than 60% and those with decreased tacrolimus dose by more than 60%. Interaction rate, rate of out of effective therapeutic range, and incidence of Graft-versus-host-disease (GVHD) and nephrotoxicity were evaluated for the two groups.
Results : Of 115 patients, the mean blood concentration of tacrolimus was significantly increased after receiving it with posaconazole (10.4 vs. 13.1 ng/mL, p < 0.0001). The interaction rate was significantly higher in the group of less than 60% reduction (37.9% vs. 19.3%, p=0.027). The rate of patients out of the effective therapeutic range was significantly different (37.2% vs. 25.5%, p = 0.018). The incidence of GVHD and nephrotoxicity were 68.7% and 71.3%, respectively.
Conclusion : Tacrolimus blood concentration was significantly increased when it was administered with posaconzole after allogenic HSCT. The interaction rate and the rate out of effective therapeutic range were significantly higher in the group of tacrolimus dose reduction by less than 60%. Thus, preemptive dose adjustment is required when tacrolimus and posaconazole enteric-coated tablets are used together in allogenic HSCT.
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KEYWORD
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Hematopoietic stem cell transplantation, Posaconazole, Tacrolimus, Immunosuppressant, Drug-drug interaction
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