WARNING: MALIGNANCIES AND SERIOUS INFECTIONS, KIDNEY GRAFT THROMBOSIS; NEPHROTOXICITY; AND MORTALITY IN HEART TRANSPLANTATION
Malignancies and Serious Infections
- Only physicians experienced in immunosuppressive therapy and management of transplant patients should prescribe Zortress. 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)]
- Increased susceptibility to infection and the possible development of malignancies such as lymphoma and skin cancer may result from immunosuppression. [See Warnings and Precautions (5.2 and 5.3)]
Kidney Graft Thrombosis
- An increased risk of kidney arterial and venous thrombosis, resulting in graft loss, was reported, mostly within the first 30 days post-transplantation. [See Warnings and Precautions (5.4)]
- Increased nephrotoxicity can occur with use of standard doses of cyclosporine in combination with Zortress. Therefore reduced doses of cyclosporine should be used in combination with Zortress in order to reduce renal dysfunction. It is important to monitor the cyclosporine and everolimus whole blood trough concentrations. [See Dosage and Administration (2.2 and 2.3) and Warnings and Precautions (5.5) and Clinical Pharmacology (12.7 and 12.8)]
Mortality in Heart Transplantation
- Increased mortality, often associated with serious infections, within the first three months post-transplantation was observed in a clinical trial of de novo heart transplant patients receiving immunosuppressive regimens with or without induction therapy. Use in heart transplantation is not recommended. [See Warnings and Precautions (5.7)]
Zortress (everolimus) is a macrolide immunosuppressant.
Zortress (EVEROLIMUS) is indicated for the following:
- Prophylaxis of organ rejection in adult patients at low-moderate immunologic risk receiving a kidney transplant.
- Use in combination with basiliximab and concurrently with reduced doses of cyclosporine and corticosteroids. (1.1)
- Use in patients at high immunologic risk is not established.
- Use for prophylaxis in organs other than kidney is not established.
- Safety and efficacy in pediatric patients (<18 years) has not been established.
Media Articles Related to Zortress (Everolimus)
Everolimus First Drug to Show Effect in Lung NETs
Source: Medscape Hematology-Oncology Headlines [2015.10.01]
Already approved for use in pancreatic neuroendocrine tumors (NETs), the drug now shows efficacy in tumors originating in lung and gastrointestinal tract.
Medscape Medical News
Novartis drug Afinitor significantly improves progression-free survival in advanced nonfunctional gastrointestinal and lung NET
Source: Endocrinology News From Medical News Today [2015.09.30]
Novartis has announced results of a Phase III pivotal study showing Afinitor® (everolimus) tablets reduced the risk of progression by 52% (hazard ratio [HR] = 0.
Promising Tx in GI Neuroendocrine Tumors
Source: MedPage Today Gastroenterology [2015.09.27]
(MedPage Today) -- Significant boosts in PFS with radiopharmaceutical, everolimus
FDA OKs New Kids' Dose of Cancer Drug
Source: MedPage Today Product Alert [2012.08.30]
WASHINGTON -- The FDA has approved a pediatric dosage of the cancer drug everolimus (Afinitor Disperz) for the treatment of a rare brain tumor.
Age, not post-op infection, more important for kidney transplant success, study finds
Source: Transplants / Organ Donations News From Medical News Today [2015.09.23]
Infection by virus cytomegalovirus (CMV) is a common and major complication following kidney transplantation.
Published Studies Related to Zortress (Everolimus)
Everolimus for subependymal giant cell astrocytoma in patients with tuberous
sclerosis complex: 2-year open-label extension of the randomised EXIST-1 study. 
continuing 4-year extension phase of EXIST-1... INTERPRETATION: These results support the longer-term use of everolimus in
A randomized phase II study of everolimus for advanced pancreatic neuroendocrine
tumors in Chinese patients. 
Everolimus, an oral inhibitor of mammalian target of mTOR, has been recently
shown to have antitumor effect in a phase III, double-blind, randomized trial
(RADIANT-3) of 410 patients with advanced pancreatic neuroendocrine tumors
(PNETs). The purpose of this study was to investigate the specific efficacy and
safety of everolimus in the Chinese patient with PNETs...
Efficacy and safety of everolimus for subependymal giant cell astrocytomas
associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised,
placebo-controlled phase 3 trial. 
subependymal giant cell astrocytomas associated with tuberous sclerosis complex... INTERPRETATION: These results support the use of everolimus for subependymal
Everolimus plus exemestane in postmenopausal patients with HR(+) breast cancer:
BOLERO-2 final progression-free survival analysis. 
this patient population... CONCLUSION: The addition of everolimus to exemestane markedly prolonged PFS in
Everolimus for previously treated advanced gastric cancer: results of the
randomized, double-blind, phase III GRANITE-1 study. 
gastric cancer... CONCLUSION: Compared with BSC, everolimus did not significantly improve overall
Clinical Trials Related to Zortress (Everolimus)
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.
Phase I/Ib Dose Escalation & Biomarker Study of Ceritinib (LDK378) + Everolimus for Locally Advanced or Metastatic Solid Tumors With an Expansion in Non-Small Cell Lung Cancer (NSCLC) Characterized by Abnormalities in Anaplastic Lymphoma Kinase (ALK) Expression [Not yet recruiting]
The goal of this clinical research study is to find the highest tolerable dose of ceritinib
(LDK378) and everolimus that can be given to patients with NSCLC or head and neck cancer.
The safety of the drug combination will also be tested.
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.
Phase 1 TheraSphere + Everolimus With Neuroendocrine Tumors (NETs) + Liver Only or Liver Dominant Disease [Withdrawn]
The goal of this clinical research study is to find the highest tolerable dose of the
combination of everolimus with TheraSphere that can be given to patients with advanced NETs
that have spread to the liver. The safety of everolimus and TheraSphere will also be
Everolimus is designed to block a protein inside the cancer cells, which is also involved in
TheraSphere is a medical device containing a radioactive material called yttrium-90 (Y-90).
Tiny glass beads called microspheres are filled with Y-90 and then injected through an
artery directly into the liver. This allows a large dose of radiation to be given directly
to the tumor, which may lower the risk of side effects from the radiation to other parts of
the body and/or to healthy liver tissue. The radiation from TheraSphere stays in the body
and begins to lose its effect within 12 days. The glass microspheres will stay in the body
from that point on. The radiation will eventually decay (go away). By the time a
participant leaves the hospital, the amount of radiation outside of the body will be low
enough to not be a threat to others.
Bevacizumab, Temsirolimus, Valproic Acid, Cetuximab [Recruiting]
The goal of this clinical research study is to find the highest tolerable dose of Avastin
(bevacizumab) and Torisel (temsirolimus) that can be given in combination with either
valproic acid or cetuximab to patients with advanced cancer that is refractory. The safety
of this drug combination will also be studied.
Bevacizumab is designed to block the growth of blood vessels, which may help to slow or
block the growth of cancer.
Temsirolimus is designed to block the growth of cancer cells, which may cause cancer cells
Valproic acid is an anti-seizure drug that may be able to activate tumor-fighting genes,
causing cancer cells to die.
Cetuximab is designed to block a certain protein, called EGFR, that is thought to cause
cancer cells to grow. This may cause cancer cells to die.
Reports of Suspected Zortress (Everolimus) Side Effects
Liver Transplant Rejection (13),
Abdominal Pain (8),
Liver Function Test Abnormal (8),
Transaminases Increased (6),
Hepatic Enzyme Increased (6),
Hepatitis C (5), more >>
Page last updated: 2015-10-01