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Pronunciation: LET-roe-zole
Class: Aromatase inhibitor

Trade Names

- Tablets 2.5 mg


A nonsteroidal competitive inhibitor of the aromatase enzyme system; inhibits the conversion of androgens to estrogens.

Slideshow: Breast Cancer Therapy: Right On Target



Rapidly and completely absorbed. Steady state reached in 2 to 6 wk.


Weakly protein bound. Vd is approximately 1.9 L/kg.


Slowly metabolized (CYP3A4, CYP2A6) to inactive metabolites.


Renal excretion of inactive metabolites is major pathway of Cl; 6% of dose recovered as unchanged letrozole. Elimination half-life is approximately 2 days.

Special Populations

Renal Function Impairment

No change in letrozole steady-state plasma concentrations in patients with moderate renal impairment (CrCl, 20 to 50 mL/min).

Hepatic Function Impairment

AUC was 37% higher in patients with mild to moderate hepatic impairment (Child-Pugh class A and B). AUC increased 2-fold and systemic Cl reduced 47% in patients with severe hepatic impairment (Child-Pugh class C).

Indications and Usage

Extended adjuvant treatment of early breast cancer in postmenopausal women who have received 5 y of adjuvant tamoxifen therapy; first-line treatment of postmenopausal women with hormone receptor–positive or hormone receptor–unknown locally advanced or metastatic cancer; advanced breast cancer in postmenopausal women with disease progression following antiestrogen therapy; adjuvant treatment of postmenopausal women with hormone receptor–positive early breast cancer.

Unlabeled Uses

Delayed puberty in adolescent males; ovulation stimulation to improve chances of pregnancy.


Women who are or may become pregnant.

Dosage and Administration


PO 2.5 mg once daily.

Hepatic Function Impairment

PO 2.5 mg every other day in patients with cirrhosis and severe hepatic impairment.

General Advice

  • Should be taken orally without regard to meals.
  • Discontinue treatment at tumor relapse.


Store between 59° and 86°F.

Drug Interactions


Plasma concentrations of letrozole may be decreased. Closely monitor for clinical and laboratory signs of reduced letrozole antitumor effects.

Adverse Reactions


Vascular disorders (54%); flushing (50%); hypertension (8%); cerebrovascular accident, thromboembolic event (3%); angina, coronary heart disease, hemiparesis, hemorrhagic or thrombotic strokes, MI, myocardial ischemia, portal vein thrombosis, pulmonary edema, thrombophlebitis, transient ischemic attacks, venous thrombosis (2% or less).


Asthenia, nervous system disorders (34%); headache (20%); dizziness (14%); fatigue, psychiatric disorders (13%); insomnia (7%); weakness (6%); somnolence (3%); anxiety, depression, vertigo (less than 5%); light-headedness (3%).


Skin disorders (32%); increased sweating (24%); night sweats (15%); rash (5%); alopecia (less than 5%); pruritus (2%); erythema multiforme, TEN (postmarketing).


Cataract (2%); blurred vision (postmarketing).


GI disorders (28%); nausea (17%); constipation (11%); diarrhea (8%); vomiting (7%); abdominal pain (6%); anorexia, renal disorders (5%); dyspepsia (4%).


Reproductive disorders (12%); breast pain (7%); UTI (6%); renal disorder, vaginal hemorrhage, vaginal irritation, vulvovaginal dryness (5%); endometrial hyperplasia/cancer (1%).


Hepatitis, increased hepatic enzymes (postmarketing).


Anaphylactic reactions, angioedema (postmarketing).


Metabolic disorders (22%); edema (18%); hypercholesterolemia (16%); increased weight (13%); decreased weight (7%); peripheral edema (5%); hypercalcemia (less than 5%); pain in extremity (4%).


Musculoskeletal disorders (38%); arthralgia/arthritis (25%); bone pain, musculoskeletal pain (22%); back pain (18%); bone fracture (14%); fracture, limb pain (10%); myalgia (9%); osteoporosis (5%); osteopenia (4%).


Dyspnea (18%); cough (13%); respiratory disorders (11%); chest wall pain (6%).


Hot flashes/flushes (34%); chest pain (8%); infections/infestations, investigations, postmastectomy lymphedema (7%); influenza, viral infection (6%); pain (5%); pleural effusion (less than 5%); second malignancies (4%).



Monitor bone mineral density (BMD) by dual-energy x-ray absorptiometry (DEXA) bone scan at baseline and annually during therapy. Monitor BMD closely in patients with osteopenia. Monitor serum cholesterol. Closely monitor for clinical and laboratory signs of reduced letrozole antitumor effects in patients taking letrozole immediately after tamoxifen.


Category X . May cause fetal harm when administered to a pregnant woman and offer no clinical benefit to premenopausal women with breast cancer. Femara is contraindicated in women who are or may become pregnant.


Undetermined. Letrozole has a very long half-life, which could lead to higher plasma levels over time. The transfer of small amounts of letrozole to an infant could seriously impair bone growth or sexual development. Discontinue breast-feeding or the drug.


Safety and efficacy not established.

Hepatic Function

Dose reduction recommended in patients with cirrhosis and/or severe hepatic impairment.

Hazardous Tasks

May cause drowsiness, fatigue, and/or dizziness.

Bone effects

May cause decreases in BMD.


An increase of at least 1.5 × ULN in total cholesterol has been observed.



Limited data available.

Patient Information

  • Advise patient that medication can be taken without regard to meals, but to take with food if stomach upset occurs.
  • Advise patient that if a dose is missed to take it as soon as possible. If close to next scheduled dose, skip the missed dose and take the next dose at the scheduled time. Caution patient not to double the dose to catch up.
  • Instruct patient to report persistent or intolerable adverse reactions to health care provider.
  • Caution patient that drug may cause drowsiness, fatigue, and/or dizziness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.
  • Inform patients of the necessity of adequate contraception in women who have the potential to become pregnant.

Copyright © 2009 Wolters Kluwer Health.