In combination with ciclosporin for microemulsion & corticosteroids for the prophylaxis of organ rejection in adult patients at low to moderate immunological risk receiving an allogeneic renal or cardiac transplant. In combination with tacrolimus & corticosteroids for the prophylaxis of organ rejection in patients receiving hepatic transplant.
At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12. In the presence of everolimus, the growth factor-stimulated phosphorylation of the p70 S6 kinase is inhibited. Since p70 S6 kinase phosphorylation is under the control of FRAP (also called m-TOR), this finding suggests that the everolimus-FKBP-12 complex binds to and thus, interferes with the function of FRAP. FRAP is a key regulatory protein which governs cell metabolism, growth and proliferation; disabling FRAP function thus explains the cell cycle arrest caused by everolimus.
Dosage & Administration
Hepatic transplant: 1 mg bd with initial dose starting 4 wk after transplantation.
Advanced Hormone Receptor-Positive, HER2-Negative Breast Cancer, Advanced NET, Advanced RCC, And Renal Angiomyolipoma With TSC: The recommended dose is 10 mg, to be taken once daily at the same time every day. Administer either consistently with food or consistently without food. Everolimus Tablets should be swallowed whole with a glass of water. Do not break or crush tablets. Continue treatment until disease progression or unacceptable toxicity occurs.
Pregnancy & Lactation
Lactation: Distribution into breast milk is unknown; not recommended
Precautions & Warnings
Elicits immunosuppressive effects and may increase risk for infections; some infections have been severe or fatal; monitor for signs and symptoms and treat promptly. Pneumocystis jiroveci pneumonia, some with a fatal outcome, reported; this may be associated with concomitant use of corticosteroids or other immunosuppressive agents
Mouth ulcers, stomatitis, and oral mucositis are common; management includes mouthwashes (without alcohol or peroxide) and topical treatments May delay wound healing and increase wound-related complications (eg, dehiscence, wound infection, incisional hernia, lymphocele, and seroma)
- Cases of renal failure (including acute renal failure), some fatal, have been observed
- May cause angioedema and fluid accumulation
- Decreases Hgb, lymphocytes, ANC, platelets; increases cholesterol, TG, glucose, creatinine
- Elevations of serum creatinine, urinary protein, blood glucose, and lipids may occur;
- decreases in hemoglobin, neutrophils, and platelets may also occur; monitor renal
- function, blood glucose, lipids, and hematologic parameters prior to treatment and periodically thereafter
- May impair male fertility
- Child-Pugh Class C hepatic impairment
- Avoid use of live vaccines during treatment and close contact with live vaccine recipients
- Can cause fetal harm when administered to a pregnant woman; advise female patients of reproductive potential to use highly effective contraception while receiving everolimus and for up to 8 weeks after ending treatment.