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Aromatase Inhibitor

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Aromatase Inhibitor, Letrozole, Femara, Anastrozole, Arimidex, Exemestane, Aromasin, Aminoglutethimide, Cytadren

  • See Also
  1. Hormonally Active Chemotherapy
  2. Endometriosis
  3. Breast Cancer Management
  • Indications
  1. Postmenopausal Breast Cancer (adjuvant treatment if Estrogen or Progesterone positive)
  2. Severe Endometriosis (off-label)
  • Contraindications
  1. Pregnancy
  2. Premenopausal women
  • Mechanism
  1. Aromatase
    1. Converts Cholesterol to pregnenolone
    2. Aromatizes peripheral androgens (Androstenedione, Testosterone) into Estrogens (estrone, Estradiol)
    3. Aromatase is a Cytochrome P-450 enzyme found on the endoplasmic reticulum of the cell
      1. Cells containing aromatase include those in the Breast, ovary and liver
  2. Aromatase Inhibitors
    1. Non-steroidal inhibitors selectively decrease circulating Estradiol levels
  • Medications
  1. Letrozole (Femara)
    1. Selective, reversible, third generation Aromatase Inhibitor
    2. More potent than Anastrozole
    3. Dosed 2.5 mg orally daily
      1. Decrease to 2.5 mg every other day in Cirrhosis or severe liver Impairment
  2. Anastrozole (Arimidex)
    1. Selective, reversible, third generation Aromatase Inhibitor
    2. Similar structure to Paclitaxel
    3. Dosed 1 mg orally daily
  3. Exemestane (Aromasin)
    1. Steroidal, synthetic androgen analog, and an irreversible Aromatase Inhibitor
    2. Dosed 25 mg orally daily
      1. Increase dose to 50 mg if concurrent use of a Strong CYP3A4 inducer
  4. Aminoglutethimide (Cytadren)
    1. Listed for historical purposes, but replaced by other Aromatase Inhibitors
    2. Synthetic derivative of glutethimide (Sedative, anticonvulsant)
    3. Blocks adrenal steroidogenesis (Cholesterol to delta5-pregnenolone)
    4. Does not decrease ovarian Estrogen production
    5. Has also been used in treating Cushing's Disease and ACTH Secreting tumors
  • Adverse Effects
  1. Osteoporosis
    1. Decreases Bone Mineral Density, and increases risks of fragility Fractures
  2. Cardiovascular Disease Risk may be increased (including CVA risk)
    1. Hyperlipidemia
    2. Hypertension
  3. Menopausal symptoms
    1. Hot Flashes
    2. Vaginal Dryness
  4. Other common adverse effects
    1. Ovarian Follicular Cysts
    2. Gastrointestinal symptoms
    3. Headaches
    4. Arthralgias and bone pain
    5. Myalgias
  • Safety
  1. Pregnancy Category X
  2. Unknown safety in Lactation
  3. Monitoring
    1. Bone Mineral Density (e.g. DEXA Scan)
    2. 25-hydroxy Vitamin D Level baseline
  • Efficacy
  1. Letrozole, Anastrazole, Exemastane appear to have similar efficacy in the adjuvant treatment of Breast Cancer
  2. More effective than Tamoxifen in reducing recurrence rates
  • Drug Interactions
  1. Tamoxifen
    1. Avoid in combination (no significant added benefit of Tamoxifen when added to Aromatase Inhibitors)
  2. Estrogens
    1. May decrease the activity of Aromatase Inhibitors
  3. Strong CYP3A4 inducers
    1. Decreases Exemestane levels (increase dose to 50 mg daily)
  • Resources
  1. Letrozole (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b73bf908-7979-4955-af20-0414388920da
  2. Anastrozole (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=acbfaaa9-503c-4691-9828-76a7146ed6de
  3. Exemestane (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=11d5a86e-7861-43f1-ae04-84daa0de7888
  • References
  1. (2012) Med Lett Drugs Ther 53(1366): 47-8 [PubMed]