II. Indications

  1. Solid Organ Transplant Immunosuppression (maintenance prevention of rejection)
    1. Not approved for Heart Transplant (increased mortality)
    2. Renal Transplant
    3. Liver Transplant
  2. Malignancy
    1. Breast Cancer (postmenopausal, advanced, Hormone receptor-positive, HER2-negative)
    2. Neuroendocrine tumors of pancreatic origin (PNET, adults, progressive)
    3. Renal Cell Carcinoma (RCC, advanced, refractory)
    4. Renal angiomyolipoma (adults not requiring immediate surgery)
    5. Tuberous sclerosis complex (TSC, adults not requiring immediate surgery)
      1. Also indicated in age >1 year with subependymal giant cell astrocytoma (SEGA, non-resectable needing treatment)

IV. Medications

  1. Everolimus (Afinitor, Zortress) tablets: 0.25 mg, 0.5 mg, 0.75 mg

V. Dosing

  1. See other references for specific dosing regimens per indication
  2. Prescribers are typically specialists knowledgeable about the risks and monitoring
  3. Decrease dose in renal dysfunction, and adjust doses based on serum levels

VI. Adverse Effects

  1. Nephrotoxicity including Proteinuria
  2. Myelosuppression
  3. Rash
  4. Delayed Wound Healing
  5. Secondary Malignancy (including Lymphoma)
  6. Male Infertility
  7. Cardiopulmonary
    1. Interstitial Lung Disease or Pulmonary fibrosis
    2. Hyperlipidemia
    3. Edema
    4. Thrombosis
      1. Hepatic artery thrombosis
      2. Kidney graft thrombosis
  8. Thrombotic Thrombocytopenic Purpura (TTP) or Hemolytic Uremic Syndrome (HUS)
    1. More common in combination with Cyclosporine
  9. Angioedema
    1. More common in combination with ACE Inhibitors
  10. Serious Infections (including Polyoma Virus Infections)
    1. Latent Viral Infection activation
    2. BK virus associated nephropathy

VII. Drug Interactions

  1. See Cytochrome P-450 3A4
  2. Many Drug Interactions
  3. Agents that increase Purine Synthesis Inhibitor concentrations
    1. Linezolid potentiates myelosuppression
    2. Erythromycin (and Clarithromycin to a lesser extent)
  4. Agents that decrease Purine Synthesis Inhibitor concentrations
    1. Rifampin
  5. Cyclosporine
    1. Decrease Cyclosporine dosing to decrease nephrotoxic effects
  6. Live Virus Vaccines
    1. Avoid while using Everolimus

VIII. Safety

  1. Avoid in Lactation
  2. Avoid in Pregnancy (despite original Pregnancy Category C designation)
    1. Use reliable Contraception during treatment and for at least 8 weeks after completion

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Related Studies

Cost: Medications

everolimus (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
EVEROLIMUS 0.5 MG TABLET Generic $12.55 each

Ontology: everolimus (C0541315)

Definition (NCI_NCI-GLOSS) A drug used to treat advanced kidney cancer that did not respond to treatment with certain other anticancer drugs. It is also being studied in the treatment of other types of cancer. Afinitor stops cancer cells from dividing and may block the growth of new blood vessels that tumors need to grow. It also decreases the body's immune responses. It is a type of immunosuppressant and a type of antiangiogenesis agent.
Definition (NCI) A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. (NCI05)
Definition (PDQ) A derivative of the natural macrocyclic lactone sirolimus with immunosuppressant and anti-angiogenic properties. In cells, everolimus binds to the immunophilin FK Binding Protein-12 (FKBP-12) to generate an immunosuppressive complex that binds to and inhibits the activation of the mammalian Target of Rapamycin (mTOR), a key regulatory kinase. Inhibition of mTOR activation results in the inhibition of T lymphocyte activation and proliferation associated with antigen and cytokine (IL-2, IL-4, and IL-15) stimulation and the inhibition of antibody production. Check for "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=372905&idtype=1" active clinical trials or "http://www.cancer.gov/Search/ClinicalTrialsLink.aspx?id=372905&idtype=1&closed=1" closed clinical trials using this agent. ("http://nciterms.nci.nih.gov:80/NCIBrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=C48387" NCI Thesaurus)
Concepts Pharmacologic Substance (T121) , Organic Chemical (T109)
MSH C107135
SnomedCT 428127005, 428698007
LNC LP65523-0, MTHU026817
English 40-O-(2-hydroxyethyl)-rapamycin, (1R,9S,12S,15R,16E,18R,19R,21R,23S,24E,26E,28E,30S,32S,35R)-1,18-Dihydroxy-12-((1R)-2-((1S,3R,4R)-4-(2-hydroxyethoxy)-3-methoxycyclohexyl)-1-methylethyl)-19,30-dimethoxy-15,17,21,23,29,35-hexamethyl-11,36-dioxa-4-azatricyclo(30.3.1.04,9)hexatriaconta-16,24,26,28-tetraene-2,3,10,14,20-pentaone, 42-O-(2-Hydroxy)ethyl Rapamycin, Everolimus, Everolimus (product), Everolimus (substance), EVEROLIMUS, SDZ-RAD, SDZ RAD, everolimus
Spanish everolimus, everolimus (sustancia), everolimus (producto)