Effect of letermovir initiation on tacrolimus concentrations among lung transplant recipients receiving concomitant azole antifungal prophylaxis

Goodlet, Kellie J.; Garcia, Rhiannon

doi:10.1111/tid.14267

Cited by 3 publications

(1 citation statement)

References 16 publications

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“…No pre-emptive tacrolimus dose adjustments occurred with LET initiation. 16 All lung transplant recipients received life-long pneumocystis prophylaxis with TMP/SMX and moldactive azole antifungal prophylaxis (most often itraconazole), which was initiated at the time of transplant and continued indefinitely for prophylaxis against coccidioidomycosis. 17…”

Section: Institutional Protocolsmentioning

confidence: 99%

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients

Martinez,

Sindu,

Nailor

et al. 2024

Transplant Infectious Dis

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BackgroundLung transplant recipients are at high risk for severe cytomegalovirus (CMV) disease. Off‐label use of letermovir (LET) may avert myelotoxicity associated with valganciclovir (VGCV), but data in lung transplantation are limited. This study aims to evaluate the outcomes of LET prophylaxis among lung transplant recipients.MethodsThis retrospective, matched cohort study included lung transplant recipients who received LET for primary CMV prophylaxis following VGCV intolerance. Patients were matched 1:1 to historical VGCV controls based on age, serostatus group, and time from transplant. The primary outcome was CMV breakthrough within 1 year post‐LET initiation; secondary outcomes included hematologic changes.ResultsA total of 124 lung transplant recipients were included per group (32% CMV mismatch, D+R‐), with LET initiated a median of 9.6 months post‐transplantation. One CMV breakthrough event (0.8%) was observed in the LET group versus four (3.2%) in the VGCV group (p = .370). The median (interquartile range) white blood cell (WBC) count was 3.1 (2.1–5.6) at LET initiation which increased to 5.1 (3.9–7.2) at the end of follow‐up (p <.001). For VGCV controls, WBC was 4.8 (3.4–7.2) at baseline and 5.4 (3.6–7.2) at the end of follow‐up; this difference was not statistically significant (p = .395). Additionally, 98.4% of LET patients experienced ≥1 leukopenia episode in the year prior to LET compared to 71.8% the year after initiation (p <.001). Similar results were observed for neutropenia (48.4% and 17.7%, p <.001).ConclusionLET prophylaxis was associated with a low rate of CMV reactivation and leukopenia recovery. LET may represent a reasonable prophylaxis option for lung transplant recipients unable to tolerate VGCV. image

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Section: Institutional Protocolsmentioning

confidence: 99%

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients

Martinez,

Sindu,

Nailor

et al. 2024

Transplant Infectious Dis

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Drug–Drug Interaction Management with the Novel Anti-Cytomegalovirus Agents Letermovir and Maribavir: Guidance for Clinicians

Burger,

Nijboer,

Ghobreyal

et al. 2024

Clin Pharmacokinet

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Letermovir and maribavir have demonstrated efficacy in the prevention and treatment, respectively, of immunosuppressed patients with cytomegalovirus (CMV) infection and disease. These patients often have polypharmacy making them at risk for drug-drug interactions. Both letermovir and maribavir can be perpetrators and victims of drug-drug interactions. Letermovir is a moderate inhibitor of CYP3A, CYP2C8 and OATP1B1/3, and a moderate inducer of CYP2C19. It is a substrate of UGT1A1/3, BCRP, P-gp and OATP1B1/3. Maribavir is a moderate CYP2C9 inhibitor and a substrate of CYP3A. Drug-drug interactions between these anti-CMV agents and a number of therapeutic classes, such as immunosuppressants, antifungal agents, and hemato-oncological agents, can have clinical consequences and deserve dose modification or close monitoring. In a number of examples, three-way drug interactions need to be assessed. The objective of this review is to provide clinicians with guidance for drug-drug interaction management, based on existing data from drug-drug interaction studies, and extrapolation to other relevant co-medications that have not (yet) been studied but that are frequently used in these patient populations.

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Universal azole prophylaxis for prevention of coccidioidomycosis among lung transplant recipients transferring care to a center within a highly endemic region

Goodlet,

Garcia,

Nailor

2024

Transplant Infectious Dis

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BackgroundCoccidioidomycosis may cause severe disseminated disease and mortality among lung transplant recipients. A strategy of lifelong azole prophylaxis was previously associated with low rates of coccidioidomycosis. Whether lung transplant recipients relocating to the Coccidioides endemic region are also at risk and would benefit from antifungal prophylaxis is unknown.MethodsLung transplant recipients transplanted at an outside center with low Coccidioides endemicity before relocating for post‐transplant follow‐up at a transplant center in Phoenix, Arizona from January 2013 to March 2024 were included. The primary outcome was proven or probable coccidioidomycosis per Mycoses Study Group consensus definitions.ResultsForty lung transplant recipients were included, with 62.5% not receiving antifungal prophylaxis at the time of transfer. The median time from transplant to relocation was 34 months. Of those not on prophylaxis, 96% were initiated on azole therapy at the first clinic visit, with 72% prescribed itraconazole. Coccidioides serologic testing was performed in 30% of the cohort, most often in the context of a broad diagnostic work‐up for suspected infection during hospitalization. After a median follow‐up of 31 months, one case (2.5%) of proven pulmonary coccidioidomycosis was identified, occurring 4.8 years post‐transplant and >2 years post‐transfer in a cystic fibrosis patient who had a pause in fluconazole prophylaxis for >1 month prior to diagnosis due to gastrointestinal intolerance and access issues. The patient was treated and maintained on isavuconazole without complications.ConclusionAzole antifungal prophylaxis was associated with a low rate of coccidioidomycosis among lung transplant recipients relocating to the highly endemic region. image

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Effect of letermovir initiation on tacrolimus concentrations among lung transplant recipients receiving concomitant azole antifungal prophylaxis

Cited by 3 publications

References 16 publications

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients

Evaluating the efficacy and safety of letermovir compared to valganciclovir for the prevention of human cytomegalovirus disease in adult lung transplant recipients

Drug–Drug Interaction Management with the Novel Anti-Cytomegalovirus Agents Letermovir and Maribavir: Guidance for Clinicians

Universal azole prophylaxis for prevention of coccidioidomycosis among lung transplant recipients transferring care to a center within a highly endemic region

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