II. Indications
- Postmenopausal Breast Cancer (adjuvant treatment if Estrogen or Progesterone positive)
- Severe Endometriosis (off-label)
III. Contraindications
- Pregnancy
- Premenopausal women
IV. Mechanism
- Aromatase
- Converts Cholesterol to pregnenolone
- Aromatizes peripheral androgens (Androstenedione, Testosterone) into Estrogens (estrone, Estradiol)
- Aromatase is a Cytochrome P-450 enzyme found on the endoplasmic reticulum of the cell
- Cells containing aromatase include those in the Breast, ovary and liver
- Aromatase Inhibitors
- Non-steroidal inhibitors selectively decrease circulating Estradiol levels
V. Medications
- Letrozole (Femara)
- Selective, reversible, third generation Aromatase Inhibitor
- More potent than Anastrozole
- Dosed 2.5 mg orally daily
- Decrease to 2.5 mg every other day in Cirrhosis or severe liver Impairment
- Anastrozole (Arimidex)
- Selective, reversible, third generation Aromatase Inhibitor
- Similar structure to Paclitaxel
- Dosed 1 mg orally daily
- Exemestane (Aromasin)
- Steroidal, synthetic androgen analog, and an irreversible Aromatase Inhibitor
- Dosed 25 mg orally daily
- Increase dose to 50 mg if concurrent use of a Strong CYP3A4 inducer
- Aminoglutethimide (Cytadren)
- Listed for historical purposes, but replaced by other Aromatase Inhibitors
- Synthetic derivative of glutethimide (Sedative, anticonvulsant)
- Blocks adrenal steroidogenesis (Cholesterol to delta5-pregnenolone)
- Does not decrease ovarian Estrogen production
- Has also been used in treating Cushing's Disease and ACTH Secreting tumors
VI. Adverse Effects
-
Osteoporosis
- Decreases Bone Mineral Density, and increases risks of fragility Fractures
- Cardiovascular Disease Risk may be increased (including CVA risk)
- Menopausal symptoms
- Other common adverse effects
- Ovarian Follicular Cysts
- Gastrointestinal symptoms
- Headaches
- Arthralgias and bone pain
- Myalgias
VII. Safety
- Pregnancy Category X
- Unknown safety in Lactation
- Monitoring
- Bone Mineral Density (e.g. DEXA Scan)
- 25-hydroxy Vitamin D Level baseline
VIII. Efficacy
- Letrozole, Anastrazole, Exemastane appear to have similar efficacy in the adjuvant treatment of Breast Cancer
- More effective than Tamoxifen in reducing recurrence rates
IX. Drug Interactions
X. Resources
- Letrozole (DailyMed)
- Anastrozole (DailyMed)
- Exemestane (DailyMed)
XI. References
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Related Studies
| letrozole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| LETROZOLE 2.5 MG TABLET | Generic | $0.11 each |
| anastrozole (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| ANASTROZOLE 1 MG TABLET | Generic | $0.11 each |
| exemestane (on 12/21/2022 at Medicaid.Gov Survey of pharmacy drug pricing) | ||
| EXEMESTANE 25 MG TABLET | Generic | $0.71 each |