|Appearance||Off White Solid|
|Boiling point||998.7±75.0 °C(Predicted)|
|solubility||Soluble in DMSO (up to 100 mg/ml) or in Ethanol (up to 100 mg/ml).|
|Water Solubility||Soluble in dimethysulfoxide,ethanol and chloroform. Slightly soluble in water.|
|RIDADR||UN 1648 3 / PGII|
|Hazardous Substances Data||159351-69-6(Hazardous Substances Data)|
Questions And Answer
IndicationsEverolimus is indicated for the treatment of numerous diseases and disorders. It indicated for the treatment of the following cases including both tumors and organ transplantation:
Patients with advance kidney cancer;
Postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer(advanced HR+ BC) in combination with exemestane, after failure of treatment with letrozole or anastrozole[8-10];
Adult patients with progressive neuroendocrine tumors of pancreatic origin(PNET) with unresectable, locally advanced or metastatic disease[9, 10];
Adult patients with advanced renal cell carcinoma(RCC) after failure of treatment with sunitinib or sorafenib;
Adult patients with renal angiomyolipoma and tuberous sclerosis complex(TSC), not requiring immediate surgery;
Pediatric and adult patients with tuberous sclerosis complex(TSC) for the treatment of subependymal giant cell astrocytoma(SEGA) that requires therapeutic intervention but cannot be curatively resected;
Adult and pediatric patients aged 2 years and older with Tuberous Sclerosis Complex(TSC)-associated partial-onset seizures;
Preventing the organ rejection during/after renal and liver transplantation[14, 15];
Progressive, well-differentiated non-functional, neuroendocrine tumors[NET] of gastrointestinal(GI) or lung origin with unresectable, locally advanced or metastatic disease. ;
OverviewEverolimus is a derivative of Rapamycin(sirolimus), and works similarly to Rapamycin as an mTOR(mammalian target of rapamycin) inhibitor[1-3]. It is currently used as an immunosuppressant to prevent rejection of organ transplants. In a similar fashion to other mTOR inhibitors, Everolimus takes effect solely on the mTORC1 protein and not on the mTORC2 protein. In transplantation medicine, it is marketed under the trade names Zortress(USA) and Certican(Europe). It has been also used for the treatment of tumors, being marketed as Afinitor(general tumours) and Votubia(tumours as a result of TSC) in oncology[5, 6]. ;
Mode of actionThe mammalian target of rapamycin(mTOR) pathway is one of the most clinically important molecular signalling networks to emerge over the past decade. It is the protein kinase at the core of this intricate and continually evolving pathway, controls cellular growth and behavior, impacting vital processes from immune reactivity to cancer progression[17, 18]. Everolimus is an mTOR inhibitor that binds with high affinity to the FK506 binding protein-12(FKBP-12), thereby forming a drug complex that inhibits the activation of mTOR[19-20]. This inhibition reduces the activity of effectors downstream, which leads to a blockage in the progression of cells from G1 into S phase, and subsequently inducing cell growth arrest and apoptosis. Everolimus also inhibits the expression of hypoxia-inducible factor, leading to a decrease in the expression of vascular endothelial growth factor[19, 20]. The result of everolimus inhibition of mTOR is a reduction in cell proliferation, angiogenesis, and glucose uptake. Since highly expression of mTOR is an important factor that promoting the cancer, blocking mTOR by Everolimus can effectively treat some kinds of cancer and the organ rejection due to immune response during/after organ transplantation[21, 22]. ;
Oral everolimus is absorbed rapidly, and reaches peak concentration after 1.3–1.8 hours. Steady state is reached within 7 days, and steady-state peak and trough concentrations, and area under the concentration-time curve (AUC), are proportional to dosage. In adults, everolimus pharmacokinetic characteristics do not differ according to age, weight or sex, but bodyweight-adjusted dosages are necessary in children.;
Adverse reactionsSome serious adverse reactions associated with Everolimus include non-infection pneumonitis, infections, severe hypersensitivity reactions, angioedema with concomitant use of ACE inhibitors, stomatitis, renal failure, impaired wound healing, metabolic disorders and myelosuppression. Various common side effects include Bloating or swelling of the face, arms, hands, lower legs, or fee bloody nose, chest pain or tightness, chills, cough, decreased weight, diarrhea, difficult or labored breathing, difficulty with swallowing, fever, general feeling of discomfort or illness, hoarseness, lower back or side pain, painful or difficult urination, rapid weight gain, sores, ulcers, or white spots on the lips, tongue, or inside the mouth and tingling of the hands or feet. Less common side effects include bleeding gums, bloody urine, blurred vision, burning, crawling, itching, numbness, prickling, or tingling feelings, coughing up blood, extreme tiredness or weakness, fast, pounding, or irregular heartbeat or pulse, increased thirst or urination, irregular breathing, loss of appetite, nausea, nervousness, nosebleeds, prolonged bleeding from cuts, red or black, tarry stools, red or dark brown urine, slow heartbeat, stomach ache, sweating, unusual tiredness or weakness and vomiting. ;
Warning and precautionsPeople who are allergic to Everolimus should be disabled. Since it can increase your risk of serious infections or getting certain cancers, such as lymphoma or skin cancer. The patients should ask their doctor about the specific risk[10, 23].
Patients who have the following conditions should consult for doctor for advice before administration: problem in digesting lactose or galactose(sugar); high cholesterol or triglycerides; liver disease; a heart transplantation; or skin cancer in them or their family members.
Since it may harm the unborn baby as well as affect fertility(the capability to have children), women should take effective birth control during administration of Everolimus and for at least eight weeks after stopping drugs. Should consult the doctor for advice if you want to or has become pregnant. It may also affect the fertility of men as well. It is generally not recommended to have breast-feed during the administration of Everolimus for women[10, 23]. ;
- Junge, G., et al. "EVEROLIMUS, MTORC1 INHIBITION, AND IMPACT ON HEPATOCELLULAR CARCINOMA RECURRENCE AFTER LIVER TRANSPLANTATION-12, 24, AND 36 MONTHS DATA FROM 719 LTX RECIPIENTS." Transplant International 27(2014]: 23-23.
- Yao, J. C., et al. "Everolimus for advanced pancreatic neuroendocrine tumors. " New England Journal of Medicine 364.6(2011]: 514-23.
- Motzer, Robert J, et al. "Nivolumab versus Everolimus in Advanced Renal-Cell Carcinoma." Lancet Oncology 17.7(2016]: 917-927.
- Nachtnebel, A. "Everolimus[Afinitor] for advanced/metastatic kidney cancer.".
- Matin, Surena F. "Everolimus for the treatment of TSC-associated tumors." Community Oncology 9.12(2012]:361–362.
- Cappellano, A. M., et al. "Successful everolimus therapy for SEGA in pediatric patients with tuberous sclerosis complex." Childs Nervous System Chns Official Journal of the International Society for Pediatric Neurosurgery 29.12(2013]:2301-2305.
- Bilbao, Itxarone, et al. "Multiple indications for everolimus after liver transplantation in current clinical practice." World Journal of Transplantation 4.2(2014]: 122-132.
- Ganschow, Rainer, et al. "The role of everolimus in liver transplantation." Clinical & Experimental Gastroenterology 7.default(2014]:329-343.
- Dunn, C, and K. F. Croom. "Everolimus: a review of its use in renal and cardiac transplantation. " Drugs 66.4(2006]:547-570.
- Geissler, Edward K., H. J. Schlitt, and G. Thomas. "mTOR, Cancer and Transplantation." American Journal of Transplantation 8.11(2010]:2212-2218.
- Young, D. A., and C. L. Nickersonnutter. "mTOR--beyond transplantation. " Current Opinion in Pharmacology 5.4(2005]: 418-423.
- Anandappa, G., A. Hollingdale, and T. Eisen. "Everolimus – a new approach in the treatment of renal cell carcinoma." Cancer Management & Research 2.1(2010]:61.
- Raimondo, L., et al. "Everolimus induces Met inactivation by disrupting the FKBP12/Met complex:" Oncotarget 7.26(2016]:40073-40084.
- Sabatini, David M. "mTOR and cancer: insights into a complex relationship." Nature Reviews Cancer 6.9(2006]:729.
- Efeyan, Alejo, and D. M. Sabatini. "mTOR and cancer: many loops in one pathway." Current Opinion in Cell Biology 22.2(2010]:169-176.