Everolimus is a macrocyclic lactone used in transplantation medicine to prevent rejection after heart and kidney transplants. It has a high structural similarity to the actinomycete-derived tacrolimus, but is produced synthetically.
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Everolimus
DefinitionThis section has been translated automatically.
Pharmacodynamics (Effect)This section has been translated automatically.
Everolimus belongs to the group of drugs called immunosuppressants. The active substance suppresses the immune response in a very specific way. Everolimus (like tacrolimus) binds with great affinity to a cytosolic receptor protein of T lymphocytes (FKBP). The resulting FKBP-everolimus complex inhibits the protein mTOR (mammalian target of rapamycin). As a key enzyme in the signal transduction of the IL-2 receptor, this kinase ensures a regulated cell cycle. The blockade of this signal transduction leads to an inhibition of the IL-2-controlled maturation and proliferation of T cells. The biological function of T cells and downstream of B cells are suppressed.
Also, proliferation processes in tumor cells, endothelial cells, fibroblasts and blood vessel-associated smooth muscle cells are suppressed.More generally, everolimus can be described as a "potent inhibitor of proliferation factors".
The mean half-life of everolimus is approximately 30.0 h.
IndicationThis section has been translated automatically.
Prophylaxis of graft rejection after kidney, heart or liver transplantation.
Advanced stages (under precisely described conditions in each case) of the following diseases:
- hormone receptor positive breast carcinoma
- neuroendocrine tumours of pancreatic origin and of lung or gastrointestinal origin
- gastrointestinal tract
- advanced renal cell carcinoma
- renal angiomyolipoma and a specific giant cell astrocytoma.
Dosage and method of useThis section has been translated automatically.
Mode of administration oral. Dosage usually 1 x 10 mg/day
Undesirable effectsThis section has been translated automatically.
Infections, anemia, angioedema, pneumonitis, stomatitis, proteinuria, renal failure (monitoring of renal function is recommended).
Other common side effects: loss of appetite, vomiting, weight loss, hyperglycemia, hypercholesterolemia, dehydration, hypokalemia, hypocalcemia, insomnia, headache, hypertension, dysphagia, dyspepsia, arthralgia, peripheral edema, fatigue.
Dermatological side effects: exanthema (including hand-foot syndrome); pruritus, nail changes, diffuse alopecia.
Note(s)This section has been translated automatically.
In many human tumors, the activity of "mTOR" is significantly increased.
LiteratureThis section has been translated automatically.
- Faivre S et al. (2006) Current development of mTOR inhibitors as anticancer agents. Nature Rev Drug Discov 5: 671-688.
- Rini B et al (2007) Temsirolimus. Nature Rev Drug Discov. 6: 599–600
- Schuler W et al. (1997) SDZ RAD, a new rapamycin derivative: pharmacological properties in vitro and in vivo. Transplantation 64: 36-42
- Sedrani, R. et al. (1998) Chemical modification of rapamycin: the discovery of SDZ RAD. Transplant Proc 30: 2192-2194 .