Conversion from sirolimus to everolimus in maintenance renal transplant recipients within a calcineurin inhibitor-free regimen: results of a 6-month pilot study

Kamar, Nassim; Jaafar, A.; Esposito, Laure; Ribes, D; Durand, Dominique; Di-Giambattista, F; Tack, Ivan; Rostaing, Lionel

doi:10.5414/cnp70118

Cited by 9 publications

(12 citation statements)

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“…42,48 Conversion from sirolimus to everolimus in kidney graft recipients or conversion from calcineurin inhibitor-based immunosuppression to an everolimus-containing therapy regimen in long-term liver graft recipients was reported in some studies. 28,38,[49][50][51] The study reporting conversion from sirolimus to everolimus in 11 kidney graft recipients observed no changes in kidney function, other laboratory parameters, rejection episodes, or cytomegalovirus infections, which is in accordance with our data. 38 We also report on our practical experience with drug dosing, which is noteworthy because no dosing recommendations are given in the European Medicines Agency and Food and Drug Administration prescribing information.…”

Section: Discussionsupporting

confidence: 91%

“…Conversion from sirolimus to everolimus in kidney graft recipients or conversion from calcineurin inhibitor–based immunosuppression to an everolimus‐containing therapy regimen in long‐term liver graft recipients was reported in some studies . The study reporting conversion from sirolimus to everolimus in 11 kidney graft recipients observed no changes in kidney function, other laboratory parameters, rejection episodes, or cytomegalovirus infections, which is in accordance with our data …”

Section: Discussionsupporting

confidence: 91%

“…In the current study, patients with a sirolimus dose of 0.5 to 1.0 mg once daily received everolimus overlapping in a ratio of 1:2 twice daily. This conversion factor was chosen because of the shorter half‐life of everolimus compared with sirolimus . Single patients with a daily sirolimus dose of 1.5 mg or higher were converted with a lower ratio at the physician's discretion.…”

Section: Methodsmentioning

confidence: 99%

“…This conversion factor was chosen because of the shorter half-life of everolimus compared with sirolimus. 26,38 Single patients with a daily sirolimus dose of 1.5 mg or higher were converted with a lower ratio at the physician's discretion. Everolimus was started and…”

Section: Conversion Protocol From Sirolimus To Everolimusmentioning

confidence: 99%

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Conversion From Sirolimus to Everolimus in Long-Term Liver Graft Recipients

Weiler

Bilge

Troetschler

et al. 2017

The Journal of Clinical Pharmacology

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Immunosuppression by inhibition of the mechanistic target of rapamycin (mTOR) is a promising approach after liver transplantation. The mTOR inhibitor sirolimus was used in selected liver graft recipients despite safety concerns and lack of approval. Everolimus is another mTOR inhibitor approved after liver transplantation. It is currently unknown, whether conversion of sirolimus to everolimus is safe in long-term liver graft recipients. Long-term liver graft recipients treated with sirolimus were converted to everolimus. A systematical analysis of biochemical and clinical data before and after conversion was performed. Sixteen patients were included (female/male, 8/8). Median (range) age at conversion was 66 years (49-78 years), and patients were converted at a median (range) of 10.1 years (4.0-22.3 years) after liver transplantation. In the majority of patients, no dose adjustment was needed after conversion. No rejection and no cytomegalovirus replication episodes were observed. Furthermore, no differences were found with respect to kidney function, diabetes mellitus, or blood pressure before and after conversion. Bilirubin serum concentration was lower, whereas aspartate aminotransaminase, alanine aminotransferase, and triglycerides serum concentrations were higher after conversion to everolimus. Neither clinical- nor graft-associated significant complications were observed after conversion from sirolimus to everolimus in long-term liver graft recipients. Everolimus-based immunosuppression may be offered to patients after liver transplantation formerly treated with sirolimus.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Conversion Protocol From Sirolimus To Everolimusmentioning

confidence: 99%

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Conversion From Sirolimus to Everolimus in Long-Term Liver Graft Recipients

Weiler

Bilge

Troetschler

et al. 2017

The Journal of Clinical Pharmacology

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“…Eleven maintenance renal-transplant patients receiving sirolimus, mycophenolic acid and corticosteroids without CNI therapy were converted to everolimus 8 mg/day (8 to 15 ng/mL). 66 Mean GFR and mean renal-phosphate threshold remained stable throughout the study and no patient died, lost their graft or experienced BPAR after conversion.…”

Section: Dovepressmentioning

confidence: 77%

The use of everolimus in renal-transplant patients

Pascual¹

2009

IJNRD

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Despite advances in immunosuppressive therapy, long-term renal-transplantation outcomes have not significantly improved over the last decade. The nephrotoxicity of calcineurin inhibitors (CNIs) is an important cause of chronic allograft nephropathy (CAN), the major driver of long-term graft loss. Everolimus is a proliferation signal inhibitor with a mechanism of action that is distinct from CNIs. The efficacy and tolerability of everolimus in renal-transplant recipients have been established in a wide range of clinical trials. Importantly, synergism between everolimus and the CNI cyclosporine (CsA) permits CsA dose reduction, enabling nephrotoxicity to be minimized without compromising efficacy. Currently, everolimus is being investigated in regimens where reduced exposure CNIs are used from the initial post-transplant period to improve renal function and prevent CAN. By inhibiting the proliferation of smooth muscle cells, everolimus may itself delay the progression or development of CAN. Although everolimus is associated with specific side effects, these can generally be managed. By targeting the main causes of short- and long-term graft loss, everolimus has a key role to play in renal transplantation, which is being explored further in a number of ongoing Phase III–IV trials.

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Inhibitors of Mammalian Target of Rapamycin

Kahan¹

2010

Immunotherapy in Transplantation

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Conversion from sirolimus to everolimus in maintenance renal transplant recipients within a calcineurin inhibitor-free regimen: results of a 6-month pilot study

Cited by 9 publications

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Conversion From Sirolimus to Everolimus in Long-Term Liver Graft Recipients

Conversion From Sirolimus to Everolimus in Long-Term Liver Graft Recipients

The use of everolimus in renal-transplant patients

Inhibitors of Mammalian Target of Rapamycin

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