Pharm

Everolimus

search

Everolimus, Afinitor, Zortress

  • See Also
  1. mTOR Inhibitor
  2. mTOR Pathway
  • 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)
  • Mechanism
  1. mTOR Inhibitor
  2. See Mammalian Target of Rapamycin Pathway (mTOR Pathway)
  • Medications
  1. Everolimus (Afinitor, Zortress) tablets: 0.25 mg, 0.5 mg, 0.75 mg
  • 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
  • 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
  • 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
  • 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
  • Resources
  1. Everolimus Oncology Indications (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=45d54974-3fc4-4237-a2fa-3158ca1a8105
  2. Everolimus Transplant Indications (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=cf2dd54b-7a1d-4401-9a01-75e68235e433
  • References
  1. Cimino (2016) Am Fam Physician 93(3): 203-10 [PubMed]
  2. Costanzo (2010) J Heart Lung Transplant 29(8): 914-56 [PubMed]