Prior Amiodarone Exposure Reduces Tacrolimus Dosing Requirements in Heart Transplant Recipients

2019 ◽  
Vol 29 (2) ◽  
pp. 129-134 ◽  
Author(s):  
Nadine T. Breslin ◽  
David M. Salerno ◽  
Veli K. Topkara ◽  
Farhana Latif ◽  
Susan Restaino ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Organ Transplant ◽  
Patient Characteristics ◽  
Tacrolimus Concentration ◽  
Transplant Recipients ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Transplant Patients ◽  
Significant Difference ◽  
And Control

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.

Primary Graft Dysfunction in Heart Transplant Recipients—Risk Factors and Longitudinal Outcomes

ASAIO Journal ◽  
2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Nicholas F. Smith ◽  
Sina Salehi Omran ◽  
Michael V. Genuardi ◽  
Edward T. Horn ◽  
Arman Kilic ◽  
...  
Keyword(s):  
Risk Factors ◽  
Heart Transplant ◽  
Transplant Recipients ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Longitudinal Outcomes ◽  
Heart Transplant Recipients

scholarly journals Evaluation of The Therapeutic Regimen in COVID-19 in Transplant Patients: Where Do Immunomodulatory and Antivirals Stand?

2021 ◽  
Author(s):  
Mojtaba Shafiekhani ◽  
Farbod Shahabinezhad ◽  
Tahmoores Niknam ◽  
Seyed Ahmad Tara ◽  
Elham Haem ◽  
...  
Keyword(s):  
Adverse Reactions ◽  
Organ Transplant ◽  
P Value ◽  
Transplant Recipients ◽  
Transplant Patients ◽  
Clinical Complications ◽  
Hospitalization Period ◽  
Significant Difference ◽  
Immunocompromised Status ◽  
Immunomodulatory Drug

Abstract Background The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. Method: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 hours before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. Results A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P-value˂0.001) and Tocilizumab as an immunomodulator drug (P-value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P-value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. Conclusion The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in SOT recipients could be promising treatments of choice to manage COVID-19.

Abstract 13933: High Urgency Candidates for Heart Transplantation Does Not Correlate to the Development of Primary Graft Dysfunction

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Rafael Skorka ◽  
Keith Nishihara ◽  
Adriana Shen ◽  
Evan P Kransdorf ◽  
Lillian Benck ◽  
...  
Keyword(s):  
Heart Transplantation ◽  
Heart Transplant ◽  
Survival Rates ◽  
Control Group ◽  
High Dose ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Assist Device ◽  
Transplant Patients ◽  
High Urgency

Introduction: Primary Graft Dysfunction (PGD) after Heart Transplantation (HTx) is seen in approximately 7-30% of heart transplant patients as described by the literature. Many of these patients have severe PGD which requires support with ECMO. It has been reported that patients who are severely ill on high dose inotropes or on assists devices have greater propensity to develop severe PGD. Many of these patients have borderline blood pressure due to poor cardiac function which may contribute to PGD with its associated vasoplegia. In order to asses risk for the development of PGD we evaluated our patients in terms of their status at the time of transplant to assess risk. Methods: Between 2010 and 2019 we assessed 44 Heart Transplant patients who developed severe PGD immediately after HTx. The UNOS Status at the time of Transplant was recorded along with the presence of a durable assist device, temporary assist device, or no Inotropes or assist device. 30 Day and 1 Year survival were assessed for all status groups including a control group (no PGD, n=799). Results: High urgency status at the time of transplant was not the overwhelming majority of patients that developed severe PGD. Approximately 32% of these patients were patients who were waiting for transplant at home, who were not on Intravenous Inotropes and not on assist devices. 1 Year survival was compromised in all patients who developed severe PGD with survival rates that were significantly lower than patients without PGD in our program (47.7% vs 93.6%, p<0.001) (see Table). Conclusions: High urgency status is not solely associated with the development of severe PGD. Further assessment into these non-urgent patients who develop severe PGD is warranted and is under investigation. Inflammatory markers should be assessed in all patients who develop severe PGD.

Abstract 14108: Does Primary Graft Dysfunction Increase First Year Intimal Thickness After Heart Transplantation?

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Keith Nishihara ◽  
Babak Azarbal ◽  
Evan P Kransdorf ◽  
Lillian Benck ◽  
Jignesh K Patel ◽  
...  
Keyword(s):  
Heart Transplant ◽  
Cell Injury ◽  
Coronary Intervention ◽  
First Year ◽  
Intimal Thickening ◽  
Primary Graft Dysfunction ◽  
Graft Dysfunction ◽  
Cardiac Events ◽  
Antibody Mediated Rejection ◽  
Transplant Patients

Introduction: Primary graft dysfunction (PGD) has been reported in between 7-30% of heart transplant recipients with severe PGD known to have poor outcome. Due to graft dysfunction and potential for endothelial cell injury, it is not known whether all grades of PGD can increase first year intimal thickening, which may be a harbinger for clinical cardiac allograft vasculopathy (CAV). Methods: Between 2010 and 2017, we assessed 769 heart transplant patients and divided them into those patients with mild PGD (n=12), moderate PGD (n=35), severe PGD (n=36) and no PGD (n=686). Endpoints included 3-year survival and freedom from angiographic CAV (stenosis ≥30%) and non-fatal major adverse cardiac events (NF-MACE: myocardial infarction, percutaneous coronary intervention, new congestive heart failure, pacemaker/implantable cardioverter-defibrillator placement, stroke); and 1-year freedom from any treated rejection (ATR), acute cellular rejection (ACR), antibody mediated rejection (AMR). First year intravascular ultrasound (IVUS) was performed at baseline 4-8 weeks and at 1 year after transplant. IVUS parameters included first-year average change in MIT and change in MIT ≥0.5mm. Results: First year change in average MIT and MIT ≥0.5mm and 3-year freedom from CAV were not significantly different in all groups. The severe PGD group compared to all groups had significantly lower 3-year survival and freedom from NF-MACE. There was lower freedom from various types of rejection in the PGD groups compared to the no PGD group. Specifically, 1-year freedom from ACR was significantly lower in the mild PGD group compared to the moderate PGD group and the no PGD group (see table). Conclusions: PGD grades do not appear to lead to increased first year intimal thickening or angiographic CAV at 3 years. Lower freedom from ACR in the mild PGD group and ATR in the severe PGD group will need further study. Larger numbers of patients are needed to confirm these findings.

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 ◽  
...  
Keyword(s):  
Plasma Concentrations ◽  
Organ Transplant ◽  
Tacrolimus Concentration ◽  
Therapeutic Drug ◽  
Solid Organ ◽  
Transplant Recipients ◽  
Dose Ratio ◽  
Transplant Patients ◽  
Daily Dose ◽  
Liver Transplant Recipients

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.

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