Lung transplantation tacrolimus

BACKGROUND & AIMS: Cystic Fibrosis (CF) liver disease progresses to liver failure requiring transplantation in about 3 % of patients, 0.7 % of CF patients are post liver transplant. The prognosis of CF has improved with the introduction of elexacaftor/tezacaftor/ivacaftor (ETI). Due to the paucity of data and concerns regarding interactions with immunosuppressive drug regimens, there is no general consensus on use of ETI post liver transplantation. The aim of this review is to report the safety and efficacy of ETI in CF patients who underwent liver transplantation...

BACKGROUND AND OBJECTIVE: High variability in tacrolimus pharmacokinetics directly after lung transplantation (LuTx) may increase the risk for acute kidney injury (AKI) and transplant rejection. The primary objective was to compare pharmacokinetic variability in patients receiving tacrolimus orally versus intravenously early after LuTx. METHODS: Pharmacokinetic and clinical data from 522 LuTx patients transplanted between 2010 and 2020 in two university hospitals were collected to compare orally administered tacrolimus to intravenous tacrolimus early post-transplantation...

BACKGROUND: Coronavirus disease 2019 (COVID-19) infection in lung transplant recipients can be lethal owing to the use of immunosuppressants. Antiviral agents may be administered to these patients. Co-packaged nirmatrelvir-ritonavir is a new agent currently being used in combination. CASE PRESENTATION: In this report, we present a case of a 64-year-old woman, a lung transplant recipient, who experienced hyponatremia and showed a high serum tacrolimus concentration following the administration of the co-packaged nirmatrelvir-ritonavir combination...

BACKGROUND: The antiviral letermovir has been increasingly used as off-label cytomegalovirus prophylaxis in solid organ transplant recipients. Observational studies have reported notable increases in tacrolimus (FK) exposure following letermovir; however, whether a significant interaction occurs in the setting of existing moderate-to-strong CYP3A4 inhibition is unknown. Therefore, the purpose of this study was to evaluate FK trough changes before and after letermovir among lung transplant recipients receiving azole antifungal prophylaxis...

INTRODUCTION: The occurrence of hyperkalemic renal tubular acidosis (RTA) in the post-transplantation period is likely underestimated, and its identification remains important to offer adequate medical management. Transplant recipients frequently present with clinical and biological characteristics that may be associated with the occurrence of this complication. METHODS: This was a single-center retrospective study that compared transplanted patients with hyperkalemic RTA and a control group to identify variables associated with the occurrence of this complication...

Background: Drug-drug interactions (DDIs) are a major but preventable cause of adverse drug reactions. There is insufficient information regarding DDIs in lung transplant recipients. Objective: This study aimed to determine the prevalence of potential DDIs (pDDIs) in intensive care unit (ICU) lung transplant recipients, identify the real DDIs and the most frequently implicated medications in this vulnerable population, and determine the risk factors associated with pDDIs. Methods: This retrospective cross-sectional study included lung transplant recipients from January 2018 to December 2021...

PURPOSE: This study aimed to investigate the potential impact of tacrolimus (TAC) exposure on clinical outcomes after lung transplantation. METHODS: This retrospective observational study enrolled a total of 228 lung transplant recipients. TAC trough levels (C0 ) were collected for 3 intervals: 0-3 months, 3-12 months, and 12-24 months. The intra-patient variability (IPV) was calculated using coefficient of variation. Genotyping of CYP3A5*3 (rs776746) was performed...

BACKGROUND: The appropriate initial dosage of tacrolimus is undefined in Chinese pediatric lung transplant patients with normal hematocrit values. The purpose of this study is to optimize the initial dose of tacrolimus in Chinese children who are undergoing lung transplantation and have normal hematocrit levels. METHODS: The present study is based on a published population pharmacokinetic model of tacrolimus in lung transplant patients and uses the Monte Carlo simulation to optimize the initial tacrolimus dosage in Chinese children with lung transplantation within normal hematocrit levels...

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a common complication after transplantation. We aim to explore potential risk factors of PTDM and its association with outcomes after lung transplantation (LTx). METHODS: A retrospective study was conducted in 100 patients who underwent LTx at our institution from 2017 to 2021. Patients' information was collected, and genotyping for single nucleotide polymorphisms known to potentially increase the risk of Type 2 DM was performed...

The determination of the appropriate initial dose for tacrolimus is crucial in achieving the target concentration promptly and avoiding adverse effects and poor prognosis. However, the trial-and-error approach is still common practice. This study aimed to establish a prediction model for an initial dosing algorithm of tacrolimus in patients receiving a lung transplant. A total of 210 lung transplant recipients were enrolled, and 26 single nucleotide polymorphisms (SNP) from 18 genes that could potentially affect tacrolimus pharmacokinetics were genotyped...

BACKGROUND: Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in heart transplant (HTx) recipients. However, previous studies of PTLD after HTx are limited to single-center analyses or extrapolated from all solid organ transplantations. OBJECTIVES: The authors analyzed the temporal trends, risk factors, and clinical outcome of de novo PTLD specifically after HTx. METHODS: Using multi-institutional, multinational data from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry, the authors evaluated the real-world data of PTLD after HTx, transplanted between January 2000 and June 2015...

INTRODUCTION: Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation. METHODS: This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes...

We present a case of a 16-year-old adolescent female with blood group O+ who was diagnosed with cystic fibrosis (CF). The patient had to be hospitalized due to septic shock and respiratory failure, and extracorporeal membrane oxygenation and mechanical ventilation were applied. Faced with high urgency, she was promptly enlisted for a lung transplant, ultimately receiving a blood group A1 deceased donor lung through rescue allocation. Bilateral incompatible lung transplantation, with parental consent, was successfully performed...

Tacrolimus is one of the calcineurin inhibitors used for maintaining immuno-suppression in thoracic and abdominal transplantations including heart, lung, liver, intestine, pancreas, and renal transplants. It has a narrow therapeutic window requiring therapeutic drug monitoring (TDM). Genetic polymorphism in the expression of cytochrome P3A5 enzyme plays a significant role in the bioavailability of tacrolimus in patients, leading to toxicity or rejection. In this case, we studied a renal transplant patient who received a standard dose of tacrolimus and experienced toxicity related to the poor expression of cytochrome P450 3A5 (CYP3A5), which required the withholding of tacrolimus and cutting the dose for several days with more frequent TDM...

OBJECTIVES: Tacrolimus (TAC) is the most widely used immunosuppressive agent after lung transplantation. Considering that the ciliary beat frequency (CBF) mainly depends on the cytoplasmic calcium concentration and that TAC can affect this due to its binding with the intracellular immunophilin FKBP12, we hypothesized that TAC could also impair the airway mucociliary clearance of rats. METHODS: Sixty rats were divided into two groups (n = 30 each): Control = water; TAC = tacrolimus...

Data on pharmacokinetics of tacrolimus during pregnancy is limited. Therefore, the aim of this retrospective study was to characterize the whole blood pharmacokinetics of tacrolimus throughout pregnancy. In this single-center retrospective cohort study whole blood tacrolimus trough concentrations (corrected for the dose; C/D ratios) were compared before, monthly during and after pregnancy in kidney, liver, and lung transplant recipients who became pregnant and gave birth between 2000 and 2022. Descriptive statistics and linear mixed models were used to characterize changes in tacrolimus C/D ratios before, during and after pregnancy...

BACKGROUND: Lung transplant recipients (LTRs) have a higher risk of hospitalization and mortality due to COVID-19 compared with the immunocompetent population. The use of nirmatrelvir/ritonavir (NR), an effective oral treatment for COVID-19, is quite challenging due to its potent drug-drug interactions with immunosuppressants and azole antifungals. As there are few clinical reports of the use of NR in LTRs, we measured tacrolimus levels in patients receiving NR in our hospital to improve safety when prescribing NR...

The triazole antifungal isavuconazole (ISAVU) is used for prevention and treatment of fungal infections in solid organ transplant (SOT). SOT recipients commonly need to transition from one azole to another due to breakthrough infection, toxicity, or other reasons. The purpose of our study was to evaluate the effect of ISAVU on immunosuppressant concentrations in thoracic transplant recipients when ISAVU was started de novo or transitioned from another azole. We conducted a single-center retrospective cohort study including 68 patients (51 lung, 14 heart, and 3 heart/lung transplant)...

Paxlovid (nirmatrelvir/ritonavir) is an antiviral drug used to treat COVID-19, nirmatrelvir, a SARS-CoV-2 main protease inhibitor, works by inhibiting viral replication in the early stages, and ritonavir is a strong cytochrome P450 (CYP) 3A inhibitor that helps the nirmatrelvir reach and maintain the therapeutic concentrations. Paxlovid has a potential risk of drug interaction by elevating the plasma concentration of other drugs metabolized by CYP3A, like tacrolimus. This report examines the case of a 57-year-old female lung transplant patient self-administered Paxlovid for 5 days without discontinuing tacrolimus...

BACKGROUND: Human natural killer (NK) cells and gamma delta (γδ) T cells may impact outcomes of solid organ transplantation (SOT) such as lung transplantation (LTx), following the differential engagement of an array of activating and inhibitory receptors. Amongst these, CD16 may be particularly important due to its capacity to bind IgG to trigger antibody-dependent cellular cytotoxicity (ADCC) and the production of proinflammatory cytokines. While the use of immunosuppressive drugs (ISDs) is an integral component of SOT practice, their relative impact on various immune cells, especially γδT cells and CD16-induced functional responses, is still unclear...