BOX WARNING: IMMUNOSUPPRESSION, EXCESS MORTALITY IN DE NOVO LIVER TRANSPLANTATION, AND BRONCHIAL ANASTOMOTIC DEHISCENCE
- Increased susceptibility to infection and the possible development of lymphoma and other malignancies may result from immunosuppression
Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal transplant patients should use Rapamune ® . Patients receiving the drug should be managed in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient [see Warnings and Precautions ( 5.1 ) ].
- Liver Transplantation – Excess Mortality, Graft Loss, and Hepatic Artery Thrombosis (HAT)
The use of Rapamune in combination with tacrolimus was associated with excess mortality and graft loss in a study in de novo liver transplant patients. Many of these patients had evidence of infection at or near the time of death.
In this and another study in de novo liver transplant patients, the use of Rapamune in combination with cyclosporine or tacrolimus was associated with an increase in HAT; most cases of HAT occurred within 30 days post-transplantation and most led to graft loss or death [see Warnings and Precautions ( 5.2 ) ].
- Lung Transplantation– Bronchial Anastomotic Dehiscence
Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when Rapamune has been used as part of an immunosuppressive regimen [see Warnings and Precautions (5.3)].
- The safety and efficacy of Rapamune (sirolimus) as immunosuppressive therapy have not been established in liver or lung transplant patients, and therefore, such use is not recommended [see Warnings and Precautions (5.2, 5.3) ].
Pharmacokinetics in Specific Populations
Rapamune® (sirolimus) is an immunosuppressive agent. Sirolimus is a macrocyclic lactone produced by
Rapamune® (sirolimus) is indicated for the prophylaxis of organ rejection in patients receiving renal transplants. It is recommended that Rapamune be used initially in a regimen with cyclosporine and corticosteroids. In patients at low to moderate immunologic risk cyclosporine should be withdrawn 2 to 4 months after transplantation and Rapamune® dose should be increased to reach recommended blood concentrations (See DOSAGE AND ADMINISTRATION).
The safety and efficacy of cyclosporine withdrawal in high-risk patients have not been adequately studied and it is therefore not recommended. This includes patients with Banff grade III acute rejection or vascular rejection prior to cyclosporine withdrawal, those who are dialysis-dependent, or with serum creatinine > 4.5 mg/dL, black patients, re-transplants, multi-organ transplants, patients with high panel of reactive antibodies (See CLINICAL STUDIES).
Media Articles Related to Rapamune (Sirolimus)
Higher cancer death rate associated with solid-organ transplant recipients
Source: Transplants / Organ Donations News From Medical News Today [2016.01.07]
In solid-organ transplant recipients, the cancer death rate was higher than in the general population in a new study from Ontario, Canada, published online by JAMA Oncology. Nancy N. Baxter, M.D.
Organ transplants: when rejection comes from within
Source: Transplants / Organ Donations News From Medical News Today [2015.12.16]
A new cellular structure responsible for previously unexplained rejection of organ transplants has been identified by researchers at the University of Montreal Hospital Research Centre (CRCHUM.
MHC class II molecules on graft endothelium promote acute rejection
Source: Transplants / Organ Donations News From Medical News Today [2016.01.22]
A limitation of organ transplant is acute rejection of the graft by the host immune system.
Published Studies Related to Rapamune (Sirolimus)
Low-dose sirolimus combined with angiotensin-converting enzyme inhibitor and statin stabilizes renal function and reduces glomerular proliferation in poor prognosis IgA nephropathy. [2011.11]
BACKGROUND: There is a lack of new therapeutic strategies for IgA nephropathy. Low-dose sirolimus inhibits mesangial cell proliferation and renal fibrosis in animal models... CONCLUSION: The addition of low-dose sirolimus to enalapril and statin is safe, stabilizes renal function and reduces glomerular proliferative lesions in patients with poor prognosis IgA nephropathy.
Biodegradable polymer versus permanent polymer drug-eluting stents and everolimus- versus sirolimus-eluting stents in patients with coronary artery disease: 3-year outcomes from a randomized clinical trial. [2011.09.20]
OBJECTIVES: The aim of this study was to compare the 3-year efficacy and safety of biodegradable polymer with permanent polymer stents and of everolimus-eluting stents (EES) with sirolimus-eluting stents (SES). BACKGROUND: Biodegradable polymer drug-eluting stents (DES) offer potential for enhanced late outcomes in comparison with permanent polymer stents. In addition, there is increasing interest in the comparison of EES (Xience, Abbott Vascular, Abbott Park, Illinois) versus SES (Cypher, Cordis Corporation, Miami Lakes, Florida)... CONCLUSIONS: Biodegradable polymer and permanent polymer DES are associated with similar clinical outcomes at 3 years. In addition, EES are comparable to SES in terms of overall clinical efficacy and safety. (Intracoronary Stenting and Angiographic Results: Test Efficacy of 3 Limus-Eluting STents [ISAR-TEST 4]: Prospective, Randomized Trial of 3-limus Agent-eluting Stents With Different Polymer Coatings; NCT00598676). Copyright (c) 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Randomized comparison of everolimus-eluting stent versus sirolimus-eluting stent implantation for de novo coronary artery disease in patients with diabetes mellitus (ESSENCE-DIABETES): results from the ESSENCE-DIABETES trial. [2011.08.23]
CONCLUSION: Everolimus-eluting stents were noninferior to sirolimus-eluting stents in reducing in-segment late loss and reduced angiographic restenosis at 8 months in patients with diabetes mellitus and coronary artery disease.
Lower malignancy rates in renal allograft recipients converted to sirolimus-based, calcineurin inhibitor-free immunotherapy: 24-month results from the CONVERT trial. [2011.08.15]
BACKGROUND: Long-term immunosuppression imposes increased malignancy risk in renal allograft recipients, significantly contributing to overall morbidity and mortality. This study examined malignancy rates in renal allograft recipients at 2 years after conversion to a sirolimus (SRL)-based, calcineurin inhibitor (CNI)-free regimen... CONCLUSION: In renal allograft recipients, SRL-based immunosuppression was associated with a lower rate of malignancy at 2 years postconversion compared with continuation of CNI-based immunosuppression. This reduction was driven by a significant reduction in nonmelanoma skin carcinoma rates; the rate of all other malignancies was numerically lower but did not achieve statistical significance.
Randomized comparison of the nobori biolimus A9-eluting stent with the sirolimus-eluting stent in patients with stenosis in native coronary arteries. [2011.07.29]
Objectives: The aim of this randomized-controlled trial is to compare Biolimus A9-eluting stent (Nobori) to sirolimus eluting stent (Cypher). Background: The Nobori coronary stent is coated only abluminally with a biodegradable polymer, poly-lactic acid, and the antiproliferative agent Biolimus A9.Both stents showed excellent midterm results.
Clinical Trials Related to Rapamune (Sirolimus)
Sirolimus or Everolimus or Temsirolimus and Vorinostat in Advanced Cancer [Recruiting]
The goal of this clinical research study is to find the highest tolerable dose of the
combination vorinostat given in combination with either sirolimus, everolimus or
temsirolimus that can be given to patients with advanced cancer. The safety of this drug
combination will also be studied.
Pharmacokinetic Drug Interaction Between Ezetimibe and Sirolimus After Single Dose Administration in Healthy Subjects [Completed]
Trial of RAD001 and Neurocognition in Tuberous Sclerosis Complex (TSC) [Completed]
Tuberous Sclerosis Complex (TSC) is a multi-system disease, usually presenting with
seizures, mental retardation and autism, and exhibiting a high variability in clinical
findings both among and within families. Investigators are doing research in order to
identify possible neurocognitive benefits from treatment with RAD001 or placebo for a six
month period. There may also be potential for improvements in seizure frequency, sleep and
autistic behaviors. We hope this trial will lead to a better understanding of TSC and to
new forms of treatment, to benefit children and adults with TSC in the future.
Individuals diagnosed with TSC will be asked to participate in this study if they are
between the ages of 6 and 21 years of age and have an IQ of greater than or equal to 60.
Both males and females will be asked to participate. Additionally, to be eligible for study
participation, individuals must have been on the same seizure medication(s), if applicable,
for at least 6 months. Individuals must also be able to participate in neuropsychological
testing and meet certain medical criteria. They will need to sign an informed consent. If
enrolled in the study, participants will have a number of screening tests to help determine
if they are eligible for participation in the clinical trial. If eligible for the treatment
phase of the trial, they will be asked to take either the study drug or a placebo (pill with
no medicine), which is determined by chance.
The study involves about 9 visits, 3 of which can be done locally, over a six month period,
as well as follow-up calls with our research nurse. Study visits will vary in length.
Screening, three month and six month visits may last up to 8 hours, while all other visits
will be less than 2 hours. The study visits include blood draws, laboratory tests and
neuropsychological assessments. There is no fee to participate in this study. Some
compensation may be available for travel costs of out-of-state participants based on fund
availability. The study drug will be provided at no charge during the study.
After all study data has been analyzed, families will be informed of the overall results.
Treatment on this study may or may not improve a child's learning skills (neurocognition).
Future patients may benefit from what is learned.
A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of a Single Dose of Sirolimus in Healthy Subjects [Completed]
Sirolimus for Autoimmune Disease of Blood Cells [Recruiting]
Treatment for patients with autoimmune destruction of blood cells is poor. The part of the
body that fights infections is called the immune system and white blood cells (WBCs) are
part of the immune system. Normally, a person's body creates WBCs to fight infections and
eliminates WBCs which have stopped helping the body function. Patients with autoimmune
destruction of blood cells have difficulty eliminating old WBCs. The abnormal WBCs build up
and can damage other healthy cells, which can lead to anemia, fatigue, jaundice, internal
bleeding, infection, and cancer. Few effective medications exist for treatment for patients
with autoimmune cytopenias and those commonly used are fraught with side effects.
Nevertheless, as scientific understanding of autoimmune diseases has improved, more directed
and less toxic therapies are becoming available. A number of groups have been studying the
efficacy of a medication called sirolimus in patients with autoimmune diseases. This
medicine has been FDA-approved for over 20 years. Sirolimus is a medicine used in children
with other diseases. Sirolimus works, in part, by eliminating old and abnormal WBCs. Our
group and others have shown that sirolimus is effective in mice with autoimmunity and in
children with a rare condition called Autoimmune Lymphoproliferative Syndrome (ALPS). We
believe sirolimus will help children with autoimmune cytopenias. We believe it will improve
their symptoms and make them less sick. We propose to study sirolimus in children with
chronic and/or refractory autoimmune cytopenias.
Reports of Suspected Rapamune (Sirolimus) Side Effects
Disease Progression (15),
Oedema Peripheral (15),
Drug Ineffective (11),
Interstitial Lung Disease (10),
Weight Decreased (9),
Graft Versus Host Disease (8), more >>
Page last updated: 2016-01-22