scholarly journals Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid-Organ Transplant Patients

2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Ryan M. Rivosecchi ◽  
Cornelius J. Clancy ◽  
Ryan K. Shields ◽  
Christopher R. Ensor ◽  
Michael A. Shullo ◽  
...  

ABSTRACT We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, the tacrolimus concentration/dose ratio normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable interpatient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly but, rather, be guided by therapeutic drug monitoring.

Author(s):  
Nataliya Zelikovsky ◽  
Debra S. Lefkowitz

The first successful organ transplant was a kidney transplant performed between identical twins in 1954. Since that time, major medical advances have been made to help improve survival rates for transplant recipients. In 2008, there were 1,964 solid organ transplants performed for children under age 18 (2007 Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients [OPTN/SRTR] Annual Report 1997–2006). Currently, approximately 1,830 pediatric patients are awaiting some type of solid organ transplant (2007 OPTN/SRTR Annual Report 1997–2006). Organ transplantation in children is relatively recent compared to other treatments for children with chronic illnesses. The focus over the first few decades has been on medical advances and improving survival rates for transplant patients. In the recent years, increasing attention has been given to the developmental, neurocognitive, and psychosocial outcomes prior to transplant and in the short-term period post transplant. Most chronic illnesses and acute traumatic medical events have implications for neurocognitive outcomes. End-stage disease of the liver, kidney, heart, and lung are all believed to affect intellectual, academic, and neurocognitive functions. Gross neurodevelopmental deficits have become less common due to early medical intervention (e.g., improved nutrition, surgical intervention, reduced exposure to aluminum (Warady 2002). Organ transplantation is believed to ameliorate the deleterious long-term developmental and neurocognitive effects, but this topic has received little attention in the literature, and the available results with regard to intellectual, academic, and neurodevelopmental results have been mixed. In a combined sample of solid organ transplant patients, 40% had clinically significant cognitive delays (Brosig et al. 2006). Examining the impact of different underlying disease processes and transplantation of each solid organ separately is critical. Thus, we discuss the neurocognitive outcomes of each organ group separately in this chapter. Neurocognitive outcomes can be assessed in a variety of ways depending upon the age of the child. Among infants and toddlers, neurocognitive functioning is measured by an assessment of motor function, social and environmental interaction, and language development. Assessment of older children may involve the evaluation of intelligence, academic achievement, emotional and behavioral functioning, and adaptive skills.


2019 ◽  
Vol 29 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Nadine T. Breslin ◽  
David M. Salerno ◽  
Veli K. Topkara ◽  
Farhana Latif ◽  
Susan Restaino ◽  
...  

Introduction: Amiodarone use prior to heart transplant is independently associated with a higher rate of severe primary graft dysfunction and in-hospital mortality. Amiodarone may also alter the pharmacokinetics of medications metabolized via cytochrome P450. No data exist regarding the interaction between pretransplant amiodarone and tacrolimus concentrations. Design: Single-center retrospective study of transplant patients between January 1, 2014, and June 30, 2016. A therapeutic tacrolimus concentration was defined as a trough level between 8 and 15 ng/mL for 2 consecutive days. The primary outcome was the tacrolimus therapeutic weight-based dosing requirements (mg/kg/day) for patients receiving amiodarone prior to transplant when compared to those without prior receipt of amiodarone. Secondary outcomes include the incidence of cellular rejection and mortality within 6 months posttransplant. Results: Multi-organ transplant recipients (n = 3), retransplants (n = 9), those who died prior to a therapeutic level (n = 1), and those receiving amiodarone posttransplant (n = 7) were excluded from the analysis. Of the 80 patients included, 34 (42%) received amiodarone prior to transplant. Patient characteristics were similar, with the exception of primary graft dysfunction incidence (38% in amiodarone vs 8.5% in control, P = .001). The median therapeutic dose was 0.1 (interquartile range [IQR]: 0.07-0.12) versus 0.13 (IQR: 0.09-0.17) in the amiodarone and control groups, respectively, ( P < .01). No significant difference in mortality or rejection was noted. Conclusion: Patients receiving amiodarone prior to transplant require a lower weight-based dose of tacrolimus.


2007 ◽  
Vol 5 (5) ◽  
pp. 541-549 ◽  
Author(s):  
Marcy Neuburg

This article explores the role of reducing immunosuppression as a therapeutic strategy for the problem of transplant-associated skin cancer. The specific issue of immunosuppression reduction is based on a brief historic review of the epidemiology of skin cancer in transplant patients, followed by a description of the role of immunosuppression as a cause of skin cancer. Finally, the literature pertaining to the hypothesis that reducing immunosuppression in solid organ transplant recipients favorably impacts both the incidence of cutaneous malignancy and outcomes relating to individual aggressive malignancies is presented.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Nuria Montero ◽  
Alexandre Favà ◽  
Anna Manonelles ◽  
José González Costello ◽  
Edoardo Melilli ◽  
...  

Abstract Background and Aims Considering the particular pharmacokinetic (PK) profile of mycophenolate (MMF/MPS) with the important contribution of enterohepatic recirculation (EHC) and the potential alteration in tacrolimus (TAC) exposure, a PK study in solid-organ transplant patients who had undergone intestinal resection was carried out. Method This is a prospective single-center study of MMF/MPS and TAC exposure changes after bowel resection and after reconstruction. Whole blood samples were collected at the following time points: 0, 0.5, 1, 1.5, 2, 4, 6, 8 and 12 hours post-dose. Areas under the curves (AUCs) were determined in both conditions: with ileostomy and after bowel reconstruction. Results Six renal and two cardiac transplant recipients were included. Four subjects completed both pre- and post-reconstruction surgery procedures. Different intestinal anatomic resections were performed (Table 1). Patients with terminal ileostomy showed an under exposure to MMF/MPS. In three patients, initial MPA levels were on target, but they decreased &gt;80% after 4 hours post-drug administration. After bowel reconstruction, the AUC increased maintaining MMF/MPA levels during 12h (Table 2). Before bowel reconstruction, TAC trough levels were within therapeutic target but, after reconstruction, AUCs normalized by dose were much higher than the expected. Conclusion Transplant recipients with ileostomy showed infra-exposure to mycophenolate. After 4 hours post-dose, MMF/MPA was undetectable because of the absence of EHC, which was recovered after anatomical correction. TAC exposure was higher after bowel reconstruction suggesting changes in the absorption. The use of mTORi in such clinical situations would be an alternative.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Samir J. Patel ◽  
Samantha A. Kuten ◽  
Richard J. Knight ◽  
Dana M. Hong ◽  
A. Osama Gaber

Ganciclovir-resistant cytomegalovirus (CMV) is associated with significant morbidity in solid organ transplant recipients. Management of ganciclovir-resistant CMV may be complicated by nephrotoxicity which is commonly observed with recommended therapies and/or rejection induced by “indirect” viral effects or reduction of immunosuppression. Herein, we report a series of four high serologic risk (donor CMV positive/recipient CMV negative) kidney transplant patients diagnosed with ganciclovir-resistant CMV disease. All patients initially developed “breakthrough” viremia while still receiving valganciclovir prophylaxis after transplant and were later confirmed to exhibit UL97 mutations after failing to eradicate virus on adequate dosages of valganciclovir. The patients were subsequently and successfully treated with reduced-dose (1-2 mg/kg) cidofovir and CMV-hyperimmune globulin, given in 2-week intervals. In addition, all patients exhibited stable renal function after completion of therapy, and none experienced acute rejection. The combination of reduced-dose cidofovir and CMV-hyperimmune globulin appeared to be a safe and effective regimen in patients with mild disease due to ganciclovir-resistant CMV.


2021 ◽  
Vol 24 (1) ◽  
pp. 22-26
Author(s):  
Maryam Chorami ◽  
Kamran Bagheri Lankarani ◽  
Fardad Ejtehadi ◽  
Seyed Ali Malek-Hosseini ◽  
Maryam Moini

Background: Chronic hepatitis E infection has been reported in solid organ transplant recipients following acute hepatitis due to the compromised immune status. Almost all reports are from areas where hepatitis E virus (HEV) genotypes 3 and 4 are the dominant genotypes. This study was conducted to investigate the role of hepatitis E infection as an etiology for liver enzymes elevation in liver transplant recipients from the largest liver transplant program in Iran. Methods: In a prospective study from June to December 2015, in a single liver transplantation center in Iran, all adult liver recipients who were investigated for the etiology of persistent elevation of liver enzymes were tested for HEV serology status. Results: Of 122 patients included in the study, 19 (15.6%) were positive for HEV serology. Seropositive patients were significantly older than seronegative ones (mean age 43.79 vs. 31.58, P < 0.001); however, they were not different in other characteristics including sex distribution and mean of liver enzymes in each occasion. Liver biopsies were done in 16 HEV seropositive patients and none of the biopsies showed evidence for acute or chronic viral hepatitis. Conclusion: In this study, with 15.6% rate of HEV seropositivity in liver recipients with persistent elevation of liver enzymes, we were not able to confirm any clinical evidence for active acute or chronic hepatitis E infection. This could theoretically be attributed to the fact that the dominant prevalent HEV genotype in our endemic area is not associated with a chronic form of infection.


2003 ◽  
Vol 16 (6) ◽  
pp. 414-433
Author(s):  
Curtis D. Holt ◽  
Gordon Ingle ◽  
Theodore M. Sievers

Before the early 1980s, patient and allograft survival for solid organ transplant recipients was dismal. By 1983, the first calcineurin blocker, cyclosporine (Sandimmun), had been introduced, and outcomes were dramatically improved. However, cyclosporine macroemulsion had suboptimal pharmacokinetics, significant drug interactions, and several adverse effects, including nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension. Recent advances with cyclosporine include the introduction of modified dosage formulations: Neoral, a microemulsion, and several generic microemulsion products. The potent second-generation calcineurin blocker tacrolimus (Prograf) was introduced in 1994 and has become the drug of choice for several types of transplant recipients. Although tacrolimus has improved pharmacokinetics and therapeutic drugmonitoring parameters, it has adverse effects such as nephrotoxicity, neurotoxicity, and diabetes. Thus, current immunosuppressive regimens implementing calcineurin blockers often involve additional immunosuppressive agents to “spare” the use of these agents, minimizing their adverse effects. This article reviews the mechanisms of action, pharmacokinetics, clinical use, therapeutic drug monitoring, drug interactions, adverse effects, and dosing of cyclosporine and tacrolimus in solid organ transplant recipients.


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