Comparison of Anti-Mold Prophylaxis and Pharmacist Impact on Tacrolimus Drug Monitoring in Heart Recipients

PurposeObjective of the study was to assess the safety and efficacy of isavuconazole (isa) vs voriconazole (vori) as anti-mold prophylaxis (ppx) and the impact on tacrolimus (FK) therapeutic drug monitoring (TDM) in heart transplant (txp) recipients.MethodsThis single center retrospective study included heart recipients transplanted between 8/19 and 3/22 who received 90 days of anti-mold ppx with vori or isa. Excluded those converted between ppx, drug interactions (DDI), died or graft loss within 90 days of txp or not on FK-based therapy. FK TDM, including levels, goal ranges, and dose changes were collected 1 month before and 2 months after end of ppx. Proactive FK dosing was conducted by pharmacists. Clinical outcomes assessed until one-year post txp and included infection, rejection, graft loss, and death. Costs analysis included prior authorizations (PA), appeals, copay, and patient assistance.Results127 patients were screened; 83 included in the final analysis; 47 patients on isa and 36 on vori. 51% on isa were African American vs 28% on vori (p=0.043). The isa group had higher normalized FK doses during and after ppx vs vori (during: 8 vs 3 mg/day; p <0.001; post: 11 vs 8 mg/day; p<0.001); FK doses were higher in isa group during ppx in multivariable models controlling for race, but not after ppx stopped. Low FK levels were more common in vori cohort during ppx (0% vs 18%; p =0.044). Vori cohort required more dose changes after ppx stopped (median 2 vs 3; p = 0.015). Rates of infection, graft loss and death were similar between cohorts. Patient copay similar between groups, with increased need for PA with isa (76% vs 33%; p <0.001).ConclusionVori and isa provided similar efficacy in preventing infections. Vori may be more challenging to manage due to more potent DDI, requiring more dose adjustments, while isa requires more resources to obtain insurance approval. Pharmacist management of DDIs, with proactive dose changes could explain the lack of difference in percentage of low levels post ppx discontinuation. Objective of the study was to assess the safety and efficacy of isavuconazole (isa) vs voriconazole (vori) as anti-mold prophylaxis (ppx) and the impact on tacrolimus (FK) therapeutic drug monitoring (TDM) in heart transplant (txp) recipients. This single center retrospective study included heart recipients transplanted between 8/19 and 3/22 who received 90 days of anti-mold ppx with vori or isa. Excluded those converted between ppx, drug interactions (DDI), died or graft loss within 90 days of txp or not on FK-based therapy. FK TDM, including levels, goal ranges, and dose changes were collected 1 month before and 2 months after end of ppx. Proactive FK dosing was conducted by pharmacists. Clinical outcomes assessed until one-year post txp and included infection, rejection, graft loss, and death. Costs analysis included prior authorizations (PA), appeals, copay, and patient assistance. 127 patients were screened; 83 included in the final analysis; 47 patients on isa and 36 on vori. 51% on isa were African American vs 28% on vori (p=0.043). The isa group had higher normalized FK doses during and after ppx vs vori (during: 8 vs 3 mg/day; p <0.001; post: 11 vs 8 mg/day; p<0.001); FK doses were higher in isa group during ppx in multivariable models controlling for race, but not after ppx stopped. Low FK levels were more common in vori cohort during ppx (0% vs 18%; p =0.044). Vori cohort required more dose changes after ppx stopped (median 2 vs 3; p = 0.015). Rates of infection, graft loss and death were similar between cohorts. Patient copay similar between groups, with increased need for PA with isa (76% vs 33%; p <0.001). Vori and isa provided similar efficacy in preventing infections. Vori may be more challenging to manage due to more potent DDI, requiring more dose adjustments, while isa requires more resources to obtain insurance approval. Pharmacist management of DDIs, with proactive dose changes could explain the lack of difference in percentage of low levels post ppx discontinuation.