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تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
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Letrozole: Drug information

Letrozole: Drug information
(For additional information see "Letrozole: Patient drug information" and see "Letrozole: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Femara
Brand Names: Canada
  • ACH-Letrozole;
  • AG-Letrozole;
  • APO-Letrozole;
  • BIO-Letrozole;
  • CCP-Letrozole [DSC];
  • Femara;
  • JAMP-Letrozole;
  • Mar-Letrozole;
  • MINT-Letrozole;
  • NAT-Letrozole;
  • NRA-Letrozole;
  • PMS-Letrozole;
  • RAN-Letrozole [DSC];
  • RIVA-Letrozole;
  • SANDOZ Letrozole;
  • TEVA-Letrozole
Pharmacologic Category
  • Antineoplastic Agent, Aromatase Inhibitor
Dosing: Adult
Breast cancer, adjuvant therapy

Breast cancer, adjuvant therapy:

Early breast cancer, adjuvant treatment: Postmenopausal patients: Oral: 2.5 mg once daily for a planned duration of 5 years; discontinue at relapse.

Early breast cancer, extended adjuvant treatment: Postmenopausal patients: Oral: 2.5 mg once daily for a planned duration of 5 years (after 5 years of tamoxifen); discontinue at relapse. In clinical trials, letrozole was initiated within 3 months of discontinuing tamoxifen (Ref).

Early breast cancer, high-risk, adjuvant treatment in premenopausal patients (off-label use): Oral: 2.5 mg once daily (in combination with ovarian function suppression) for a duration of 5 years (Ref).

Duration of adjuvant endocrine therapy: American Society of Clinical Oncology (ASCO) guidelines for adjuvant endocrine therapy for women with hormone receptor–positive (HR+) breast cancer (focused update) recommend a duration of 5 to 10 years of adjuvant endocrine therapy; some patients may be appropriate candidates for extended aromatase inhibitor (AI) therapy for up to a total of 10 years based on disease recurrence risk and nodal disease status. Refer to the guidelines for specific recommendations based on menopausal status and tolerability (Ref). Treatment with an additional 5 years of AI therapy (for a total of 10 years of endocrine therapy) demonstrated a significantly improved rate of disease-free survival and a decreased risk of disease recurrence and contralateral breast cancer (when compared to placebo); although, overall survival was not significantly different between groups, and bone-related adverse events occurred more frequently with letrozole versus placebo (Ref).

Breast cancer, advanced, first- or second-line treatment

Breast cancer, advanced, first- or second-line treatment: Postmenopausal patients: Oral: 2.5 mg once daily; continue until tumor progression.

Breast cancer off-label combinations

Breast cancer off-label combinations:

Breast cancer, advanced, estrogen receptor-positive, HER2-negative, first-line treatment: Postmenopausal patients: Oral: 2.5 mg once daily (in combination with palbociclib) until disease progression or unacceptable toxicity (Ref) or 2.5 mg once daily (in combination with ribociclib) until disease progression or unacceptable toxicity (Ref) or 2.5 mg once daily (in combination with abemaciclib) until disease progression or unacceptable toxicity (Ref).

Breast cancer, metastatic, hormone receptor–positive, HER2-positive: Postmenopausal patients: Oral: 2.5 mg once daily (in combination with lapatinib) until disease progression or unacceptable toxicity (Ref).

Breast cancer, metastatic, hormone receptor–positive, HER2-positive, salvage therapy: Postmenopausal patients: Oral: 2.5 mg once daily (in combination with trastuzumab and lapatinib) until disease progression or unacceptable toxicity (Ref). Note: Patients in the study had received prior endocrine therapy and had disease progression during or after a prior regimen containing trastuzumab plus chemotherapy in the neo(adjuvant) setting and/or first-line metastatic setting.

Breast cancer in male patients, hormone receptor–positive

Breast cancer in male patients, hormone receptor–positive (off-label use): Note: Should be used in combination with a gonadotropin-releasing hormone agonist/antagonist (Ref).

Adjuva nt therapy (alternative agent): May be used as adjuvant therapy in male patients with hormone receptor–positive (HR+) breast cancer with a contraindication to tamoxifen. ASCO guidelines for management of male breast cancer recommend an initial duration of 5 years of adjuvant endocrine therapy; if there still is a high risk of recurrence, 5 additional years of endocrine therapy may be offered if the initial 5 years of adjuvant therapy have been completed and tolerated (Ref).

Advanced or metastatic disease: Oral: 2.5 mg once daily until disease progression or unacceptable toxicity (Ref). Endocrine therapy for males with advanced or metastatic, HR+, HER2-negative breast cancer may be sequenced as in females (Ref).

Infertility/Ovulation stimulation in anovulatory patients with polycystic ovary syndrome

Infertility/Ovulation stimulation in anovulatory patients with polycystic ovary syndrome (off-label use): Initial dose: Oral: 2.5 mg once daily for 5 days, starting on day 3, 4, or 5 following menses or progestin induced bleed; may increase to 5 mg/day for 5 days in subsequent cycles if ovulation does not occur. Maximum dose: 7.5 mg/day (Ref). Dosing for up to 5 cycles was used in 1 study (Ref).

Ovarian cancer, epithelial, recurrent

Ovarian cancer, epithelial, recurrent (off-label use): Oral: 2.5 mg once daily; continue until disease progression or unacceptable toxicity (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function: No dosage adjustment necessary for any degree of kidney dysfunction (Ref).

Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (lipophilic and relatively large Vd): No supplemental dose or dosage adjustment necessary (Ref).

Peritoneal dialysis: Unlikely to be dialyzed (lipophilic and relatively large Vd): No dosage adjustment necessary (Ref).

CRRT: No dosage adjustment necessary (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (Ref).

Dosing: Hepatic Impairment: Adult

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.

Severe impairment (Child-Pugh class C) and cirrhosis: 2.5 mg every other day

Noncirrhotic patients with elevated bilirubin: There are no dosage adjustments provided in the manufacturer's labeling (effect has not been determined).

Dosing: Adjustment for Toxicity: Adult

Hyperlipidemia: May require antihyperlipidemic medication.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Letrozole: Pediatric drug information")

Constitutional delay of growth and puberty

Constitutional delay of growth and puberty (CDGP): Limited data available: Male Adolescents ≥14 years: Oral: 2.5 mg once daily with or without testosterone therapy (Ref). A phase 3 randomized comparative controlled trial in adolescent males (n= 30; mean age: ~15 years; testosterone group n=15; letrozole n=15) reported subjects treated with letrozole showed higher levels of the puberty markers LH, FSH, testosterone, and inhibin B and significantly greater testicular growth compared to the testosterone treatment group (Ref). When used in combination with testosterone, bone maturation was delayed, predicted adult height values were significantly increased, and markers of puberty progressed during the 12 months of therapy (Ref).

McCune-Albright syndrome; precocious puberty

McCune-Albright syndrome; precocious puberty: Very limited data available: Female Children >2 to 8 years at time of treatment initiation: Oral: Initial: 0.5 mg/m2/day in divided doses every 12 hours for days 1 to 7, then 1 mg/m2/day in divided doses every 12 hours on days 8 to 14, then 1.5 mg/m2/day in divided doses every 12 hours beginning on day 15; if needed, may further increase to 2 mg/m2/day in divided doses if markers of precocious puberty including serum estradiol levels continue to progress. Dosing based on a pilot study of nine girls (3 to 8 years at time of therapy initiation) which showed long-term therapy (up to 36 months) decreased rates of growth and bone maturation; although ovarian volume decreased during the first 6 months of treatment, the mean ovarian volume increased over 1 to 2 years of therapy with cyst redevelopment in some patients. During the pilot study, dosing was divided twice daily to alleviate GI discomfort; however, pharmacokinetic analysis showed once daily dosing would be appropriate for young children if tolerated (Ref). In a case series (n=3, age range at treatment: 3 to 7 years), a fixed dose of 2.5 mg once daily was used for 5 to 19 months duration (Ref).

Short stature; idiopathic

Short stature; idiopathic: Limited data available: Male Children ≥9 years and Adolescents <17 years: Oral: 2.5 mg once daily. Dosing based on experience in a double-blind, placebo-controlled trial of 30 males (treatment group: n=16; age range: 9 to 14 years) and a retrospective observation (n=24; age range: 9 to 16 years); the duration of letrozole therapy was up to 2 years (range: 4 to 24 months); bone maturation delay with increases in predicted adult height values were observed with treatment (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, data suggests no dosage adjustment is required.

Dosing: Hepatic Impairment: Pediatric

There are no pediatric-specific recommendations; based on experience in adult patients, dosing adjustment suggested.

Adverse Reactions (Significant): Considerations
Bone mineral density loss/increased fracture risk

Letrozole is associated with a decreased bone mineral density (BMD); decreases (from baseline) in total hip and lumbar spine BMD have been reported. Letrozole has been linked to bone resorption in postmenopausal females, an increased risk of osteoporosis and bone fracture should be considered with administering treatment (Ref).

Mechanism: Time-related; letrozole decreases plasma estrogen levels. Low levels of estrogen have been linked to bone resorption leading to decreased BMD, especially at the lumbar spine and hip. This results in increased risk of osteoporosis and fracture (Ref).

Onset: Delayed; bone loss occurred during the first 2 years of treatment (Ref).

Risk factors:

• Longer durations of aromatase inhibitors (>3 years of therapy) (Ref)

• Preexisting known risk factors for BMD loss, osteoporosis, and fracture; includes preexisting osteopenia, age >65 years, years since menopause, body mass index <20 kg/m2, personal/family history, chronic glucocorticoid use >6 months, prior fragility fracture history, low bone mineral density, rheumatoid arthritis, and smoking (Ref)

Ischemic cardiovascular events

Ischemic heart disease has been reported, with an increased incidence of ischemic cardiovascular events in patients with preexisting ischemic heart disease. Angina pectoris and acute myocardial infarction (MI) have occurred.

Mechanism: Non–dose-related; idiosyncratic. Aromatase inhibitors (AI), such as letrozole, reduce the protective effects of estrogen, consequently leading to increases in vasoconstriction and atherosclerosis. Additionally, there is dysregulation of lipid metabolism and potential risk of hyperlipidemia. Together, these factors may increase the risk of cardiovascular disease (CVD) in patients receiving AI for breast cancer treatment (Ref).

Onset: Varied; cardiac ischemia may occur at any time during treatment (Ref).

Risk factors:

• Preexisting CVD (including ischemic heart disease) or risk factors associated with CVD. In a large SEER-Medicare cohort evaluating MI risk with adjuvant hormone therapy, several preexisting conditions were associated with MI including diabetes with complications, heart failure, prior MI, coronary artery disease, and peripheral vascular disease. In patients with prior history of MI, hazard ratio was nearly 3-fold higher (Ref).

• Longer durations of AI therapy (>3 years of therapy) are associated with 18% to 26% increased risk of CVD (Ref).

Musculoskeletal effects

Musculoskeletal effects (including new onset or exacerbation of existing arthralgia, joint stiffness, and/or ostealgia) may occur with letrozole (Ref). Aromatase inhibitor-induced arthralgia presents with symmetrical joint pains most commonly affecting hands, wrists, and knees (Ref). Tenosynovitis (trigger finger) and carpal tunnel syndrome may also be common complaints (Ref). These adverse reactions may significantly affect quality of life and the risk of treatment nonadherence or discontinuation should be considered (Ref).

Mechanism: Non–dose-related; idiosyncratic. Exact mechanism is unknown; however, multiple mechanisms have been proposed involving estrogen depletion either as a direct or indirect cause. Proposed estrogen depletion mechanisms include direct local effects on joint tissues, increased inflammatory parameters, such as IL-6 indirectly affecting central and peripheral nociception (Ref), decreased estradiol leading to a decrease in endogenous opioid levels (Ref), collagen degradation, and impaired regulation of cartilage structure (Ref).

Onset: Varied; the median time to onset of symptoms is 1.6 months with a range of 0.4 to 10 months. Symptoms have been shown to peak ~6 months after initiation of treatment (Ref).

Risk factors:

• Prior menopausal hormone therapy and previous chemotherapy (Ref)

• Certain CYP19A1 single nucleotide polymorphisms (SNPs) have been associated with increased arthralgia symptoms and/or association with discontinuation of therapy due to intolerable arthralgia (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Edema (7% to 18%), flushing (50%)

Dermatologic: Diaphoresis (24%), night sweats (15%)

Endocrine & metabolic: Hot flash (19% to 34%), hypercholesterolemia (52%), weight gain (13%)

Gastrointestinal: Nausea (9% to 17%)

Nervous system: Dizziness (3% to 14%), fatigue (10% to 13%)

Neuromuscular & skeletal: Arthralgia (≤25%) (table 1), arthritis (≤25%) (table 2), asthenia (6% to 34%) (table 3), back pain (5% to 18%), bone fracture (10% to 15%), ostealgia (5% to 22%) (table 4), osteoporosis (5% to 15%) (table 5)

Letrozole: Adverse Reaction: Arthralgia

Drug (Letrozole)

Comparator

Placebo

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Number of Patients (Placebo)

Comments

≤25%

≤21%

N/A

Adjuvant treatment of early breast cancer

2,448

2,447

N/A

Comparator: Tamoxifen; described as "arthralgia/arthritis"

22%

N/A

18%

Adjuvant treatment of early breast cancer

2,563

N/A

2,573

N/A

16%

15%

N/A

First-line treatment of advanced breast cancer

455

455

N/A

Comparator: Tamoxifen

Letrozole: Adverse Reaction: Arthritis

Drug (Letrozole)

Comparator

Placebo

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Number of Patients (Placebo)

Comments

≤25%

≤21%

N/A

Adjuvant treatment of early breast cancer

2,448

2,447

N/A

Comparator: Tamoxifen; described as "arthralgia/arthritis"

7%

N/A

5%

Adjuvant treatment of early breast cancer

2,563

N/A

2,573

N/A

Letrozole: Adverse Reaction: Asthenia

Drug (Letrozole)

Comparator

Placebo

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Number of Patients (Placebo)

Comments

34%

N/A

32%

Adjuvant treatment of early breast cancer

2,563

N/A

2,573

N/A

6%

4%

N/A

First-line treatment of advanced breast cancer

455

455

N/A

Comparator: Tamoxifen

Letrozole: Adverse Reaction: Ostealgia

Drug (Letrozole)

Comparator

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Comments

5%

5%

Adjuvant treatment of early breast cancer

2,448

2,447

Comparator: Tamoxifen

22%

21%

First-line treatment of advanced breast cancer

455

455

Comparator: Tamoxifen

Letrozole: Adverse Reaction: Osteoporosis

Drug (Letrozole)

Comparator

Placebo

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Number of Patients (Placebo)

Comments

15%

N/A

8%

Adjuvant treatment of early breast cancer

N/A

N/A

N/A

N/A

12%

N/A

6%

Adjuvant treatment of early breast cancer

N/A

N/A

N/A

N/A

5%

3%

N/A

Adjuvant treatment of early breast cancer

2,448

2,447

N/A

Comparator: Tamoxifen

Respiratory: Cough (13%), dyspnea (6% to 18%)

1% to 10%:

Cardiovascular: Acute myocardial infarction (1% to 2%) (table 6), angina pectoris (1%) (table 7), cardiac failure (1% to 2%), cerebrovascular accident (≤3%), chest pain (6% to 8%), chest wall pain (6%), hemorrhagic stroke (≤2%), hypertension (6% to 8%), peripheral edema (5%), thromboembolism (≤3%; including portal vein thrombosis, pulmonary embolism, thrombophlebitis, venous thrombosis), thrombotic stroke (≤2%), transient ischemic attacks (≤3%)

Letrozole: Adverse Reaction: Acute Myocardial Infarction

Drug (Letrozole)

Comparator

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Comments

2%

1%

Adjuvant treatment of early breast cancer

2,448

2,447

At median follow-up of 96 months; comparator: Tamoxifen

1%

0.5%

Adjuvant treatment of early breast cancer

2,448

2,447

At median treatment duration of 60 months; comparator: Tamoxifen

Letrozole: Adverse Reaction: Angina Pectoris

Drug (Letrozole)

Comparator

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Comments

1%

1%

Adjuvant treatment of early breast cancer

2,448

2,447

Angina pectoris requiring surgery; at median follow-up of 96 months; comparator: Tamoxifen

1%

1%

Adjuvant treatment of early breast cancer

2,448

2,447

Angina pectoris requiring surgery; at median treatment duration of 60 months; comparator: Tamoxifen

Dermatologic: Alopecia (3%)

Endocrine & metabolic: Weight loss (6% to 7%)

Gastrointestinal: Anorexia (≤4%), constipation (2% to 10%), diarrhea (8%), vomiting (3% to 7%)

Genitourinary: Mastalgia (2% to 7%), urinary tract infection (6%), vaginal hemorrhage (5%), vaginal irritation (5%)

Hematologic & oncologic: Lymphedema (7%; post-mastectomy), second primary malignant neoplasm (2% to 5%)

Infection: Infection (7%), influenza (6%)

Nervous system: Depression (5%), headache (4% to 8%), hemiparesis (≤2%), insomnia (6% to 7%), lethargy (<10%), malaise (<10%), pain (5%)

Neuromuscular & skeletal: Limb pain (4% to 10%), myalgia (7% to 9%) (table 8), osteopenia (4%) (table 9)

Letrozole: Adverse Reaction: Myalgia

Drug (Letrozole)

Comparator

Placebo

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Number of Patients (Placebo)

Comments

9%

9%

N/A

Adjuvant treatment of early breast cancer

2,448

2,447

N/A

Comparator: Tamoxifen

7%

N/A

5%

Adjuvant treatment of early breast cancer

2,563

N/A

2,573

N/A

Letrozole: Adverse Reaction: Osteopenia

Drug (Letrozole)

Comparator

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Comments

4%

3%

Adjuvant treatment of early breast cancer

2,448

2,447

Comparator: Tamoxifen

Ophthalmic: Cataract (2%)

Renal: Renal disease (5%)

<1%:

Cardiovascular: Ischemic heart disease (table 10)

Letrozole: Adverse Reaction: Ischemic Heart Disease

Drug (Letrozole)

Comparator

Indication

Number of Patients (Letrozole)

Number of Patients (Comparator)

Comments

0.2%

0.4%

Adjuvant treatment of early breast cancer

2,448

2,447

Comparator: Tamoxifen

Endocrine & metabolic: Ovarian cyst

Genitourinary: Endometrial hyperplasia

Hematologic & oncologic: Endometrial carcinoma, thrombocytopenia

Postmarketing:

Cardiovascular: Arterial thrombosis, hypersensitivity angiitis (Kim 2020), palpitations, prolonged QT interval on ECG (Grouthier 2018), tachycardia, ventricular arrhythmia (Grouthier 2018)

Dermatologic: Erythema multiforme, erythema nodosum (Kim 2020), skin rash (Finn 2016), toxic epidermal necrolysis (Chia 2006), urticaria, xeroderma (Finn 2016)

Endocrine & metabolic: Increased thirst

Gastrointestinal: Abdominal pain (Finn 2016), dysgeusia (Finn 2016), dyspepsia (Finn 2016), increased appetite, stomatitis (Finn 2016), xerostomia

Genitourinary: Urinary frequency, vaginal discharge

Hematologic & oncologic: Anemia (Finn 2016), leukopenia (Finn 2016), neutropenia (Finn 2016)

Hepatic: Hepatitis

Hypersensitivity: Anaphylaxis, angioedema

Nervous system: Anxiety (Finn 2016), carpal tunnel syndrome (Niravath 2013), dysesthesia, irritability (Goodwin 2006), memory impairment, nervousness, paresthesia

Neuromuscular & skeletal: Decreased bone mineral density (Perez 2006), subacute cutaneous lupus erythematosus (Kim 2020), tenosynovitis (trigger finger) (Niravath 2013)

Ophthalmic: Blurred vision, dry eye syndrome (Turaka 2013), eye irritation

Miscellaneous: Fever (Finn 2016)

Contraindications

Known hypersensitivity to letrozole or any component of the formulation; pregnancy.

Canadian labeling: Additional contraindications (not in the US labeling): Hypersensitivity to other aromatase inhibitors; use in patients <18 years of age; premenopausal patients; breastfeeding.

Warnings/Precautions

Concerns related to adverse effects:

• CNS depression: May cause dizziness, fatigue, and somnolence; patients should be cautioned before performing tasks which require mental alertness (eg, operating machinery or driving).

• Increased cholesterol: May increase total serum cholesterol. In patients treated with adjuvant therapy and cholesterol levels within normal limits, an increase of ≥1.5 x ULN in total cholesterol (nonfasting) has been demonstrated in 8.2% of letrozole-treated patients (25% requiring lipid-lowering medications) versus 3.2% of tamoxifen-treated patients (16% requiring medications).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Femara: 2.5 mg

Generic: 2.5 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Femara Oral)

2.5 mg (per each): $31.79

Tablets (Letrozole Oral)

2.5 mg (per each): $10.41 - $18.13

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Femara: 2.5 mg [contains corn starch]

Generic: 2.5 mg

Administration: Adult

Oral: Administer without regard to meals.

Administration: Pediatric

Oral: May administer without regard to meals.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Breast cancer in postmenopausal patients:

Adjuvant treatment of hormone receptor-positive early breast cancer.

Extended adjuvant treatment of early breast cancer after 5 years of adjuvant tamoxifen therapy.

First-line treatment of hormone receptor-positive, locally-advanced or metastatic breast cancer.

Treatment of advanced breast cancer in patients with disease progression following antiestrogen therapy.

Use: Off-Label: Adult

Breast cancer, high-risk, hormone receptor–positive, adjuvant endocrine therapy in premenopausal patients (in combination with ovarian function suppression); Breast cancer in male patients, hormone receptor–positive; Infertility/Ovulation stimulation in anovulatory patients with polycystic ovary syndrome; Ovarian (epithelial) cancer, recurrent

Medication Safety Issues
Sound-alike/look-alike issues:

Femara may be confused with Famvir, femhrt, Provera

Letrozole may be confused with anastrozole

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs that have a heightened risk of causing significant patient harm when used in error.

International issues:

Letaris, a formerly marketed Dutch brand name product for letrozole, may be confused with Letairis, a US brand name for ambrisentan.

Metabolism/Transport Effects

Substrate of CYP2A6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Levomethadone: Aromatase Inhibitors may increase the serum concentration of Levomethadone. Risk C: Monitor therapy

Methadone: Aromatase Inhibitors may increase the serum concentration of Methadone. Risk C: Monitor therapy

Nintedanib: Letrozole may increase the serum concentration of Nintedanib. Risk C: Monitor therapy

Tamoxifen: May decrease the serum concentration of Letrozole. Risk X: Avoid combination

Reproductive Considerations

A pregnancy test is recommended prior to starting letrozole therapy in all patients who could become pregnant.

When used for management of breast cancer, effective contraception should be used during letrozole therapy and for at least 3 weeks following the last letrozole dose.

Letrozole is used off-label for ovulation induction in patients with polycystic ovarian syndrome (PCOS) and anovulatory infertility when no other causes of infertility are present (ACOG 194 2018; Teede 2018). Baseline pregnancy testing is done prior to letrozole therapy to rule out unexpected ovulation, which prevents exposure in early pregnancy (Legro 2016). Because data related to newborn outcomes following maternal use are limited, guidelines recommend counseling patients of the off-label status prior to use (ACOG 194 2018).

Pregnancy Considerations

Use is contraindicated in patients with an established pregnancy.

Based on the mechanism of action and data from animal reproduction studies, letrozole may cause fetal harm if used during pregnancy.

Breastfeeding Considerations

It is not known if letrozole is present in breast milk.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for at least 3 weeks after the letrozole last dose.

Dietary Considerations

Calcium and vitamin D supplementation are recommended.

Monitoring Parameters

Hormone receptor status. Hepatic function tests (at baseline); consider monitoring cholesterol panel and bone mineral density. Evaluate pregnancy status (prior to treatment in patients who could become pregnant). Monitor adherence.

For infertility/ovarian stimulation (off-label use), a pregnancy test is recommended prior to initiation. Midluteal progestin concentrations (in a clinical study, nonresponse to treatment was defined as a progesterone concentration <3 ng/mL during the midluteal phase; poor ovulatory response was defined as progesterone concentrations indicating ovulation but just above the cutoff point) (Legro 2014).

Cardiovascular monitoring for patients with breast cancer: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; estimate 10-year cardiovascular disease risk in patients without cardiovascular disease at baseline; assess cardiovascular risk annually in patients with a high 10-year risk (ASCO [Armenian 2017]; ESC [Lyon 2022]).

Mechanism of Action

Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system which binds to the heme group of aromatase, a cytochrome P450 enzyme which catalyzes conversion of androgens to estrogens (specifically, androstenedione to estrone and testosterone to estradiol). This leads to inhibition of the enzyme and a significant reduction in plasma estrogen (estrone, estradiol and estrone sulfate) levels. Letrozole does not appear to affect synthesis of adrenal or thyroid hormones, aldosterone, or androgens.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: Rapid and well absorbed; not affected by food

Distribution: Vd: ~1.9 L/kg

Protein binding, plasma: Weak

Metabolism: Hepatic via CYP3A4 and 2A6 to an inactive carbinol metabolite

Half-life elimination: Terminal: ~2 days

Time to steady state, plasma: 2 to 6 weeks; steady state serum concentrations are 1.5 to 2 times higher than single-dose values. In girls 3 to 9 years, steady state concentrations were 25% to 67% that of the mean adult values (Feuillan 2007)

Excretion: Urine (~90%; 6% as unchanged drug, 75% as glucuronide carbinol metabolite, 9% as unidentified metabolites)

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

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

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Cinfaletro | Femara | Letara | Letrozole denk | Rozlet;
  • (AR) Argentina: Cendalon | Cravetol | Fada letrozol | Femara | Idelara | Ingelet | Letrofarm gp pharm | Letrozol Biotenk | Letrozol eczane | Letrozol gen med | Letrozol glenmark | Letrozol hlb | Letrozol microsules | Letrozol varifarma | Trotech | Veuen;
  • (AT) Austria: Femara | Letrofam | Letrozol +pharma | Letrozol accord | Letrozol actavis | Letrozol Arcana | Letrozol Bluefish | Letrozol G.L. | Letrozol Genericon | Letrozol Kabi | Letrozol Medico Uno | Letrozol Ratiopharm | Letrozol Sandoz | Letrozol stada;
  • (AU) Australia: Apo letrozole | Chemmart letrozole | Femara | Femolet | Fera | Gynotril | Letara | Letroz | Letrozole actavis | Letrozole an | Letrozole drla | Letrozole fbm | Letrozole ga | Letrozole gh | Letrozole rbx | Letrozole sandoz | Letrozole synthon | Lezole | Pharmacor letrozole | Pharmacy choice letrozole | Stada letrozole | Terry white chemists letrozole;
  • (BD) Bangladesh: Femara | Femzole | Fezol | Lenor | Letrogen | Ovazol | Zoleta;
  • (BE) Belgium: Femara | Letrozarom | Letrozol actavis | Letrozole accord | Letrozole apotex | Letrozole EG | Letrozole Mylan | Letrozole sandoz | Letrozole teva;
  • (BF) Burkina Faso: Letero;
  • (BG) Bulgaria: Clarzole | Femara | Letrocon | Letrofemin | Letrogratis | Letrozol Nucleus | Letrozole alvogen | Letrozole neopharma | Letrozole winthrop | Lortanda | Zequipra;
  • (BR) Brazil: Breelet | Femara | Ivevi | Lefemi | Lemol | Letrozol | Letrozol bergamo/amgen | Letrozol blau | Liliya | Noazy | Sabine | Soletre;
  • (CH) Switzerland: Femara | Letrozol actavis | Letrozol devatis | Letrozol helvepharm | Letrozol labatec | Letrozol Mylan | Letrozol orion | Letrozol Sandoz | Letrozol teva | Letrozol Zentiva;
  • (CI) Côte d'Ivoire: Letero | Ranmast;
  • (CL) Chile: Femara | Letrovitae | Letrozol | Losiral | Tiadis;
  • (CN) China: Femara | Fu rui | Letrozol;
  • (CO) Colombia: Creatinon | Femara | Femgard | Gesamaf | Hb oncobreast | Latoren | Let | Letara | Letmam | Letoval | Letro seven | Letrocare | Letrole | Letroz | Letrozol | Lezoria;
  • (CZ) Czech Republic: Aletro | Apo letrozol | Arofek | Brenea | Dracenax | Etruzil | Femara | Lerana | Lestara | Letmylan | Letromedac | Letrovena | Letrozol +pharma | Letrozol apotex | Letrozol Mylan | Letrozol Ratiopharm | Letrozol stada | Letrozol teva | Letrozole Medico Uno | Letrozole Pharmacenter | Likarda | Ninivet | Oncozol | Trozara | Trozel;
  • (DE) Germany: Femar | Femara | Letro cell | Letroarom | Letroblock | Letrohexal | Letromedac | Letrozol 1 A Pharma | Letrozol 1a pharma | Letrozol AbZ | Letrozol accord | Letrozol actavis | Letrozol AL | Letrozol Aristo | Letrozol Axios | Letrozol Beta | Letrozol Biomo | Letrozol Bluefish | Letrozol CT | Letrozol denk | Letrozol devatis | Letrozol Dura | Letrozol Fair Med Healthcare | Letrozol glenmark | Letrozol Haemato | Letrozol hetero | Letrozol Heumann | Letrozol Hormosan | Letrozol Kabi | Letrozol onkovis | Letrozol Pfizer | Letrozol puren | Letrozol Q | Letrozol Ratiopharm | Letrozol stada | Letrozol sun | Letrozol Tecnimede | Letrozol Winthrop;
  • (DO) Dominican Republic: Losiral | Lupriza | Trozet;
  • (EC) Ecuador: Antif | Femara | Losiral | Lupriza;
  • (EE) Estonia: Femara | Letrozol Ratiopharm | Letrozole accord | Letrozole Genericon | Letrozole polpharma | Letrozole Swiss | Letrozole teva | Lortanda;
  • (EG) Egypt: Femapent | Femara | Letrotume;
  • (ES) Spain: Devazol | Femara | Galdar | Letrozol accord | Letrozol actavis | Letrozol Almus | Letrozol alter | Letrozol apotex | Letrozol Bluefish | Letrozol Cinfamed | Letrozol Combix | Letrozol Kern pharma | Letrozol mabo | Letrozol Mylan | Letrozol Normon | Letrozol Pensa | Letrozol pensa pharma | Letrozol Ratiopharm | Letrozol Sandoz | Letrozol stada | Letrozol sun | Letrozol tarbis | Letrozol Tecnigen | Letrozol teva | Letrozol vir | Letrozol Winthrop | Loxifan | Zarax;
  • (ET) Ethiopia: Femara | Letrozol denk | Mamazol;
  • (FI) Finland: Femar | Letrolan | Letrozol accord | Letrozol actavis | Letrozol Arrow | Letrozol Mylan | Letrozol orifarm | Letrozol orion | Letrozol Ratiopharm | Letrozol teva | Letrozole bluefish | Letrozole sandoz | Letrozole Stada;
  • (FR) France: Femara | Letrozole accord healthcare | Letrozole almus | Letrozole alter | Letrozole Arrow | Letrozole biogaran | Letrozole bluefish | Letrozole cristers | Letrozole EG | Letrozole evolugen | Letrozole Isomed | Letrozole Mylan | Letrozole phr lab | Letrozole ranbaxy | Letrozole ratiopharm | Letrozole sandoz | Letrozole Sun | Letrozole teva | Letrozole Zentiva | Letrozole Zydus;
  • (GB) United Kingdom: Femara | Letrozole Arrow | Letrozole sandoz | Letrozole teva;
  • (GR) Greece: Aromed | Femara | Femazac | Leoncon | Letropen | Letrozin | Letrozole Specifar | Letrozole teva | Letrozole/generics | Letrozole/mylan | Levinox | Linol | Mimor | Ratroz | Religan | Stefaplex | Trezor | Viobrest;
  • (HK) Hong Kong: Femara | Letrozol Farmoz;
  • (HR) Croatia: Avomit | Femara | Lametta | Letrilan | Letrofar | Letrozol actavis | Letrozol Genera | Letrozol JGL | Letrozol Sandoz | Siletris;
  • (HU) Hungary: Etruzil | Famos | Femara | Letromataz | Letronorm | Letrovena | Letrozol actavis | Letrozol Kabi | Letrozol phace | Letrozol Polpharma | Letrozol Ratiopharm | Letrozol Sandoz | Letrozole bluefish | Letrozole Medico Uno | Letrozole mediner | Letrozole Mylan | Letrozole Pharmacenter | Letrozole teva | Lexeroll | Lortanda | Ninivet | Picozone;
  • (ID) Indonesia: Aromara | Femaplex | Femara | Lebrest | Lezra | Trozet;
  • (IE) Ireland: Eirfem | Femara | Letrozole actavis | Letrozole bluefish | Letrozole Mylan | Letrozole teva | Letzo;
  • (IL) Israel: Femara;
  • (IN) India: Anolet | Aromatin | Brelet | Caditraz | Ccq l | Celofem | Chemlet | Clomipure l | Culet | E ova l | Evatrol | Fabova | Femara | Fempro | Feofer | Fertolet | Fertroz | Foliripe | Folletro | Goodova l | Herhope | Herlet | Induz | Letall | Letero | Letisha | Letnine | Letov | Letoval | Letozis | Letpro | Letroact | Letrocyt | Letrofil | Letroher | Letrohope | Letrolife | Letromac | Letronat | Letrova | Letroz | Letsi | Letzol | Lutrozole | Lytrol | Mamazol | Momazol | Newova | Oncolet | Oneova | Oreta | Ova plus l | Samlet | Stimu Let | Stimucor | Stimufol | Stimulet | Trozet | Zolet | Zuvitroz;
  • (IS) Iceland: Letromal;
  • (IT) Italy: Brestoral | Calantha | Femara | Gosuran | Letrix | Letrozolo | Letrozolo Actavis | Letrozolo AHCL | Letrozolo almus | Letrozolo alter | Letrozolo Crinos | Letrozolo Doc Generici | Letrozolo fidia | Letrozolo germed | Letrozolo Mylan | Letrozolo pensa | Letrozolo Sandoz | Letrozolo Sun | Letrozolo tecnigen | Letrozolo Teva | Letrozolo Zentiva;
  • (JO) Jordan: Estrodex | Etofem | Fempro | Lefftara;
  • (JP) Japan: Femara | Letrozole ffp | Letrozole sandoz;
  • (KE) Kenya: Femara | Fempro | Glotraz | Intez | Letero | Letroday | Letrofem | Letrol | Letroz;
  • (KR) Korea, Republic of: Bretra | Esmara | Femara | Lenara | Letron | Pamellar | Parnuel | Peratra | Teva letrozole | Trozet;
  • (KW) Kuwait: Femara;
  • (LB) Lebanon: Apo letrozole | Emvia | Femaplex | Femara | Femazol | Lefftara | Letrozole Arrow | Letrozole biogaran | Letrozole bluefish | Trozet;
  • (LT) Lithuania: Femara | Letrozol Polpharma | Letrozol Ratiopharm | Letrozole accord | Letrozole sanoswiss | Letrozole teva | Likarda | Picozone;
  • (LU) Luxembourg: Femara | Letrozole EG;
  • (LV) Latvia: Femara | Letrozole Genericon | Letrozole ratiopharm | Letrozole sanoswiss | Letrozole teva | Likarda;
  • (MA) Morocco: Femara | Femolet | Letrozole cooper | Letrozole zenith;
  • (MX) Mexico: Asuletus | Bionontrol | Femara | Gesamaf | Leroz | Letrozol | Letz | Rajendra | Solestrasa in | Trodis | Zolstro;
  • (MY) Malaysia: Femara | Lebreta | Letara | Letero | Letronat | Trozet;
  • (NG) Nigeria: Drecan | Femara | Impregnil | Letrozole denk;
  • (NL) Netherlands: Femara | Letroman | Letrozol | Letrozol accord | Letrozol actavis | Letrozol CF | Letrozol focus | Letrozol Mylan | Letrozol Sandoz | Letrozol sun | Letrozol teva;
  • (NO) Norway: Femar | Femara | Letrozol | Letrozol accord | Letrozol medical valley | Letrozol Mylan | Letrozol orifarm | Letrozole sandoz;
  • (NZ) New Zealand: Femara | Letara | Letraccord | Letrole | Letromyl;
  • (PE) Peru: Antif | Fecinole | Femara | Let | Letrovitae | Letrozol;
  • (PH) Philippines: Celofem | Dracenax | Femara | Hentrozole | Letero | Letoripe | Letov | Letrostad | Letroz | Letvex | Lezra | Mamazol;
  • (PK) Pakistan: Adezol | Aqate | Aromek | Avegest | Bloozol | Breta | Cansa | Cellzol | Febres | Femaget | Femaplex | Femara | Femizole | Femol | Fempro | Fetrozole | Fimra | Hilet | Interoz | Latromina | Leep | Leerose | Letara | Letfer | Letocor | Letonko | Letorel | Letova | Letra | Letraben | Letramed | Letrasan | Letrazo | Letrodrx | Letrofold | Letrofoz | Letrolex | Letrowrd | Lets | Letson | Letz sure | Letzole | Lezra | Litrazon | Litrex | Livazole | Losiral | Mamozol | Medlee | Oreta | Osume | Senora | Shelet | Sliczole | Synlet | Tapestro | Troza | Trozet | Trozo | Trozol | U salet | Walzole | Wimzole | Zolara | Zolix | Zomed | Zor;
  • (PL) Poland: Apo Letro | Arogen | Aromek | Clarzole | Etruzil | Femara | Lametta | Letralan | Letromedac | Letrozol teva | Letrozole accord | Letrozole apotex | Letrozole bluefish | Letrozolum polpharma | Lortanda | Lostar | Mionic | Symletrol | Trozebax;
  • (PR) Puerto Rico: Femara;
  • (PT) Portugal: Femara | Letrozol | Letrozol accord | Letrozol actavis | Letrozol alter | Letrozol Farmoz | Letrozol Generis | Letrozol Hikma | Letrozol Kabi | Letrozol Pharmakern | Letrozol Sandoz | Letrozol stada | Letrozol synthon | Letrozol Tecnimede | Letrozol teva | Letrozol Tolife;
  • (PY) Paraguay: Famara | Fecinole | Femara | Letroz | Letrozol bioteng | Letrozol gebina | Letrozol imedic | Letrozol intas | Letrozol microsules | Letrozol quimfa | Letrozol seven | Letrozol suntec | Letrozol tuteur | Letrozol varifarma | Losiral | Lupriza;
  • (QA) Qatar: Femara;
  • (RO) Romania: Elozora | Etruzil | Femara | Letralan | Letrozol atb | Letrozol stada | Letrozol teva | Lezra | Lortanda | Trozel | Zequipra | Zotrol;
  • (RU) Russian Federation: Estrolet | Etruzil | Extraza | Femara | Lestrodex | Letrose | Letrosun | Letrotera | Letroza | Letrozol | Letrozole teva | Loreta | Nexazole | Oreta;
  • (SA) Saudi Arabia: Apo letrozole | Femaplex | Femara | Lefftara | Letara | Pms letrozole | Rozlet;
  • (SE) Sweden: Femar | Letrozol 2care4 | Letrozol abacus medicine | Letrozol accord | Letrozol actavis | Letrozol Arrow | Letrozol ebb | Letrozol medical valley | Letrozol Mylan | Letrozol orifarm | Letrozol orion | Letrozol stada | Letrozol teva | Letrozole bluefish | Letrozole sandoz;
  • (SG) Singapore: Femara | Letero | Letrozole sandoz;
  • (SI) Slovenia: Femara | Femtozone | Lenizol | Letrozol teva | Lotestrol | Picozone;
  • (SK) Slovakia: Aletro | Brenea | Clarzole | Etruzil | Femara | Letromyl | Letrovena | Letrozol +pharma | Letrozol Mylan | Letrozol Polpharma | Letrozol Ratiopharm | Letrozol Sandoz | Letrozol stada | Letrozol teva | Letrozole Medico Uno | Letrozole Pharmacenter | Lidiozol | Lortanda | Ninivet | Oralet | Trozel;
  • (TH) Thailand: Femara | Letero | Letov | Letrozole alvogen | Trozet;
  • (TN) Tunisia: Femaplex | Femara | Gynotril | Lefftara | Letrozole actavis | Letrozole neapolis;
  • (TR) Turkey: Femara | Letrasan | Letroks | Letrol | Letu;
  • (TW) Taiwan: Femara | Lenozole | Letara | Letero | Letramase | Letrozole alvogen | Trozet;
  • (UA) Ukraine: Aralet | Etruzil | Femara | Lesra | Letero | Letoripe | Letromara | Letrotera | Letrovista | Letrozol | Letrozole genepharm | Letrozole krka | Letrozole vista ac;
  • (UG) Uganda: Chemlet | Letero | Letrozole denk;
  • (UY) Uruguay: Fecinole | Femara | Letrofarm | Letroz | Lupriza;
  • (VE) Venezuela, Bolivarian Republic of: Letrozol;
  • (ZA) South Africa: Accord letrozole | Cipla letrozole | Femara | Femzole | Laradex | Letraz | Letrozole hetero | Trozolt;
  • (ZM) Zambia: Oncolet | Trozet;
  • (ZW) Zimbabwe: Femara | Letero | Letrasan
  1. <800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
  2. American College of Obstetricians and Gynecologists (ACOG) Committee on Practice Bulletins—Gynecology. American College of Obstetricians and Gynecologists Practice Bulletin No. 194: polycystic ovary syndrome. Obstet Gynecol. 2018;131(6):e157-e171. doi: 10.1097/AOG.0000000000002656. [PubMed 29794677]
  3. Amir E, Seruga B, Niraula S, Carlsson L, Ocaña A. Toxicity of adjuvant endocrine therapy in postmenopausal breast cancer patients: a systematic review and meta-analysis. J Natl Cancer Inst. 2011;103(17):1299-1309. doi:10.1093/jnci/djr242 [PubMed 21743022]
  4. Armenian SH, Lacchetti C, Barac A, et al. Prevention and monitoring of cardiac dysfunction in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017;35(8):893-911. doi:10.1200/JCO.2016.70.5400 [PubMed 27918725]
  5. Balen AH, Morley LC, Misso M, et al. The management of anovulatory infertility in women with polycystic ovary syndrome: an analysis of the evidence to support the development of global WHO guidance. Hum Reprod Update. 2016;22(6):687-708. [PubMed 27511809]
  6. Bercaw-Pratt JL, Moorjani TP, Santos XM, Karaviti L, Dietrich JE. Diagnosis and management of precocious puberty in atypical presentations of McCune-Albright syndrome: a case series review. J Pediatr Adolesc Gynecol. 2012;25(1):e9-e13. doi:10.1016/j.jpag.2011.09.005 [PubMed 22051789]
  7. Borrie AE, Rose FA, Choi YH, et al. Genetic and clinical predictors of arthralgia during letrozole or anastrozole therapy in breast cancer patients. Breast Cancer Res Treat. 2020;183(2):365-372. doi:10.1007/s10549-020-05777-1 [PubMed 32632513]
  8. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO clinical practice guideline focused update. J Clin Oncol. 2019;37(5):423-438. doi:10.1200/JCO.18.01160 [PubMed 30452337]
  9. Burstein HJ, Lacchetti C, Anderson H, et al. Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: American Society of Clinical Oncology clinical practice guideline update on ovarian suppression. J Clin Oncol. 2016;34(14):1689-1701. doi:10.1200/JCO.2015.65.9573 [PubMed 26884586]
  10. Buzdar AU, Robertson JF, Eiermann W, Nabholtz JM. An overview of the pharmacology and pharmacokinetics of the newer generation aromatase inhibitors anastrozole, letrozole, and exemestane. Cancer. 2002;95(9):2006-2016. doi:10.1002/cncr.10908 [PubMed 12404296]
  11. Chia WK, Lim YL, Greaves MW, Ang P. Toxic epidermal necrolysis in patient with breast cancer receiving letrozole. Lancet Oncol. 2006;7(2):184-185. doi:10.1016/S1470-2045(06)70581-2 [PubMed 16455483]
  12. Chirgwin JH, Giobbie-Hurder A, Coates AS, et al. Treatment adherence and its impact on disease-free survival in the Breast International Group 1-98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol. 2016;34(21):2452-2459. doi:10.1200/JCO.2015.63.8619 [PubMed 27217455]
  13. Coates AS, Keshaviah A, Thurlimann B, et al, “Five Years of Letrozole Compared With Tamoxifen as Initial Adjuvant Therapy for Postmenopausal Women With Endocrine-Responsive Early Breast Cancer: Update of Study BIG 1-98,” J Clin Oncol, 2007, 25(5):486-92. [PubMed 17200148]
  14. Crew KD, Greenlee H, Capodice J, et al. Prevalence of joint symptoms in postmenopausal women taking aromatase inhibitors for early-stage breast cancer. J Clin Oncol. 2007;25(25):3877-3883. doi:10.1200/JCO.2007.10.7573 [PubMed 17761973]
  15. De Laet C, Kanis JA, Odén A, et al. Body mass index as a predictor of fracture risk: a meta-analysis. Osteoporos Int. 2005;16(11):1330-1338. doi:10.1007/s00198-005-1863-y [PubMed 15928804]
  16. De Laurentiis M, Borstnar S, Campone M, et al. Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population. Breast Cancer Res Treat. 2021;189(3):689-699. doi:10.1007/s10549-021-06334-0 [PubMed 34414532]
  17. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials. Lancet Oncol. 2022;23(3):382-392. doi:10.1016/S1470-2045(21)00758-0 [PubMed 35123662]
  18. Expert opinion. Senior Renal Editorial Team: Kenar D. Jhaveri, MD; Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
  19. Femara (letrozole) [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; May 2020.
  20. Femara (letrozole) [product monograph]. Dorval, Quebec, Canada: Novartis Pharmaceuticals Canada Inc; October 2022.
  21. Feuillan P, Calis K, Hill S, Shawker T, Robey PG, Collins MT. Letrozole treatment of precocious puberty in girls with McCune-Albright syndrome: a pilot study. J Clin Endocrinol Metab. 2007;92:2100-2106. [PubMed 17405850]
  22. Finn RS, Martin M, Rugo HS, et al. Palbociclib and letrozole in advanced breast cancer. N Engl J Med. 2016;375(20):1925-1936. doi:10.1056/NEJMoa1607303 [PubMed 27959613]
  23. Franik S, Eltrop SM, Kremer JA, et al. Aromatase inhibitors (letrozole) for subfertile women with polycystic ovary syndrome. Cochrane Database Syst Rev. 2018;5:CD010287. doi: 10.1002/14651858.CD010287.pub3. [PubMed 29797697]
  24. Gaillard S, Stearns V. Aromatase inhibitor-associated bone and musculoskeletal effects: new evidence defining etiology and strategies for management. Breast Cancer Res. 2011;13(2):205. doi:10.1186/bcr2818 [PubMed 21457526]
  25. Goetz MP, Toi M, Campone M, et al. MONARCH 3: Abemaciclib as initial therapy for advanced breast cancer. J Clin Oncol. 2017;35(32):3638-3646. [PubMed 28968163]
  26. Goldvaser H, Barnes TA, Šeruga B, et al. Toxicity of extended adjuvant therapy with aromatase inhibitors in early breast cancer: a systematic review and meta-analysis. J Natl Cancer Inst. 2018;110(1):10.1093/jnci/djx141. doi:10.1093/jnci/djx141 [PubMed 28922781]
  27. Goodwin GM. Aromatase inhibitors and bipolar mood disorder: a case report. Bipolar Disord. 2006;8(5 Pt 1):516-518. doi:10.1111/j.1399-5618.2006.00367.x [PubMed 17042891]
  28. Goss PE, Ingle JN, Martino S, et al. A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer. N Engl J Med. 2003;349(19):1793-1802. [PubMed 14551341]
  29. Goss PE, Ingle JN, Pritchard KI, et al. Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years. N Engl J Med. 2016;375(3):209-219. [PubMed 27264120]
  30. Grouthier V, Lebrun-Vignes B, Glazer AM, et al. Increased long QT and torsade de pointes reporting on tamoxifen compared with aromatase inhibitors. Heart. 2018;104(22):1859-1863. doi:10.1136/heartjnl-2017-312934 [PubMed 29720397]
  31. Hadji P, Jackisch C, Bolten W, et al. COMPliance and Arthralgia in Clinical Therapy: the COMPACT trial, assessing the incidence of arthralgia, and compliance within the first year of adjuvant anastrozole therapy. Ann Oncol. 2014;25(2):372-377. doi:10.1093/annonc/mdt513 [PubMed 24355487]
  32. Haque R, Shi J, Schottinger JE, et al. Cardiovascular disease after aromatase inhibitor use. JAMA Oncol. 2016;2(12):1590-1597. doi:10.1001/jamaoncol.2016.0429 [PubMed 27100398]
  33. Hassett MJ, Somerfield MR, Baker ER, et al. Management of male breast cancer: ASCO guideline. J Clin Oncol. 2020;38(16):1849-1863. doi:10.1200/JCO.19.03120 [PubMed 32058842]
  34. Henry NL, Giles JT, Ang D, et al. Prospective characterization of musculoskeletal symptoms in early stage breast cancer patients treated with aromatase inhibitors. Breast Cancer Res Treat. 2008;111(2):365-372. doi:10.1007/s10549-007-9774-6 [PubMed 17922185]
  35. Hero M, Norjavaara E, Dunkel L. Inhibition of estrogen biosynthesis with a potent aromatase inhibitor increases predicted adult height in boys with idiopathic short stature: a randomized controlled trial. J Clin Endocrinol Metab. 2005;90:6396-6402. [PubMed 16189252]
  36. Hortobagyi GN, Stemmer SM, Burris HA, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18):1738-1748. [PubMed 27717303]
  37. Hortobagyi GN, Stemmer SM, Burris HA, et al. Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer. Ann Oncol. 2018;29(7):1541-1547. doi:10.1093/annonc/mdy155 [PubMed 29718092]
  38. Hu S, Yu Q, Wang Y, et al. Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2018;297(5):1081-1088. doi: 10.1007/s00404-018-4688-6 [PubMed 29392438]
  39. Im SA, Lu YS, Bardia A, et al. Overall survival with ribociclib plus endocrine therapy in breast cancer. N Engl J Med. 2019;381(4):307-316. doi:10.1056/NEJMoa1903765 [PubMed 31166679]
  40. Jin H, Tu D, Zhao N, et al. Longer-term outcomes of letrozole versus placebo after 5 years of tamoxifen in the NCIC CTG MA.17 trial: analyses adjusting for treatment crossover. J Clin Oncol. 2012;30:718-721. [PubMed 22042967]
  41. Johnston S, Pippen J Jr, Pivot X, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol. 2009;27(33):5538-5546. [PubMed 19786658]
  42. Johnston SRD, Hegg R, Im SA, et al. Phase III, randomized study of dual human epidermal growth factor receptor 2 (HER2) blockade with lapatinib plus trastuzumab in combination with an aromatase inhibitor in postmenopausal women with HER2-positive, hormone receptor-positive metastatic breast cancer: updated results of ALTERNATIVE. J Clin Oncol. 2021;39(1):79-89. doi:10.1200/JCO.20.01894 [PubMed 32822287]
  43. Kamaraju S, Shi Y, Smith E, Nattinger AB, Laud P, Neuner J. Are aromatase inhibitors associated with higher myocardial infarction risk in breast cancer patients? A Medicare population-based study. Clin Cardiol. 2019;42(1):93-100. doi:10.1002/clc.23114 [PubMed 30443921]
  44. Kanis JA, Johansson H, Johnell O, et al. Alcohol intake as a risk factor for fracture. Osteoporos Int. 2005;16(7):737-742. doi:10.1007/s00198-004-1734-y [PubMed 15455194]
  45. Kanis JA, Johansson H, Oden A, et al. A family history of fracture and fracture risk: a meta-analysis. Bone. 2004;35(5):1029-1037. doi:10.1016/j.bone.2004.06.017 [PubMed 15542027]
  46. Kanis JA, Johansson H, Oden A, et al. A meta-analysis of prior corticosteroid use and fracture risk. J Bone Miner Res. 2004;19(6):893-899. doi:10.1359/JBMR.040134 [PubMed 15125788]
  47. Kanis JA, Johnell O, De Laet C, et al. A meta-analysis of previous fracture and subsequent fracture risk. Bone. 2004;35(2):375-382. doi:10.1016/j.bone.2004.03.024 [PubMed 15268886]
  48. Kanis JA, Johnell O, Oden A, et al. Smoking and fracture risk: a meta-analysis. Osteoporos Int. 2005;16(2):155-162. doi:10.1007/s00198-004-1640-3 [PubMed 15175845]
  49. Karmazin A, Moore WV, Popovic J, Jacobson JD. The effect of letrozole on bone age progression, predicted adult height, and adrenal gland function. J Pediatr Endocrinol Metab. 2005;18:285-293. [PubMed 15813607]
  50. Kim YJ, Cohen PR. Anastrozole-induced dermatitis: report of a woman with an anastrozole-associated dermatosis and a review of aromatase inhibitor-related cutaneous adverse events. Dermatol Ther (Heidelb). 2020;10(1):221-229. doi:10.1007/s13555-020-00353-3 [PubMed 31965545]
  51. Legro RS. Ovulation induction in polycystic ovary syndrome: current options. Best Pract Res Clin Obstet Gynaecol. 2016;37:152-159. doi: 10.1016/j.bpobgyn.2016.08.001. [PubMed 27866938]
  52. Legro RS, Brzyski RG, Diamond MP, et al; NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome. N Engl J Med. 2014;371(2):119-29. doi: 10.1056/NEJMoa1313517. [PubMed 25006718]
  53. Lombard JM, Zdenkowski N, Wells K, et al. Aromatase inhibitor induced musculoskeletal syndrome: a significant problem with limited treatment options. Support Care Cancer. 2016;24(5):2139-2146. doi:10.1007/s00520-015-3001-5 [PubMed 26556210]
  54. Lyon AR, López-Fernández T, Couch LS, et al; ESC Scientific Document Group. 2022 ESC guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022;43(41):4229-4361. doi:10.1093/eurheartj/ehac244 [PubMed 36017568]
  55. Matthews A, Stanway S, Farmer RE, et al. Long term adjuvant endocrine therapy and risk of cardiovascular disease in female breast cancer survivors: systematic review. BMJ. 2018;363:k3845. doi:10.1136/bmj.k3845 [PubMed 30297439]
  56. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801-1811. doi:10.1056/NEJM199906103402306 [PubMed 10362825]
  57. Mieog JS, Morden JP, Bliss JM, Coombes RC, van de Velde CJ; IES Steering Committee. Carpal tunnel syndrome and musculoskeletal symptoms in postmenopausal women with early breast cancer treated with exemestane or tamoxifen after 2-3 years of tamoxifen: a retrospective analysis of the Intergroup Exemestane Study. Lancet Oncol. 2012;13(4):420-432. doi:10.1016/S1470-2045(11)70328-X [PubMed 22265698]
  58. Misso ML, Wong JL, Teede HJ, et al. Aromatase inhibitors for PCOS: a systematic review and meta-analysis. Hum Reprod Update. 2012;18(3):301-312. [PubMed 22431566]
  59. Niravath P. Aromatase inhibitor-induced arthralgia: a review. Ann Oncol. 2013;24(6):1443-1449. doi:10.1093/annonc/mdt037 [PubMed 23471104]
  60. Palmert MR, Dunkel L. Clinical practice. Delayed puberty. N Engl J Med. 2012;366(5):443-453. [PubMed 22296078]
  61. Perez EA, Josse RG, Pritchard KI, et al. Effect of letrozole versus placebo on bone mineral density in women with primary breast cancer completing 5 or more years of adjuvant tamoxifen: a companion study to NCIC CTG MA.17. J Clin Oncol. 2006;24(22):3629-3635. doi:10.1200/JCO.2005.05.4882 [PubMed 16822845]
  62. Perrone F, De Laurentiis M, De Placido S, et al. Adjuvant zoledronic acid and letrozole plus ovarian function suppression in premenopausal breast cancer: HOBOE phase 3 randomised trial. Eur J Cancer. 2019;118:178-186. doi:10.1016/j.ejca.2019.05.004 [PubMed 31164265]
  63. Piacentini F, Omarini C, Barbieri E. Lapatinib and renal impairment: a case report. Tumori. 2013;99(3):e134-135. doi:10.1177/030089161309900334 [PubMed 24158084]
  64. Presant CA, Bosserman L, Young T, et al. Aromatase inhibitor-associated arthralgia and/ or bone pain: frequency and characterization in non-clinical trial patients. Clin Breast Cancer. 2007;7(10):775-778. doi:10.3816/CBC.2007.n.038 [PubMed 18021478]
  65. Ramirez PT, Schmeler EM, Milam MR, et al, “Efficacy of Letrozole in the Treatment of Recurrent Platinum- and Taxane-Resistant High-Grade Cancer of the Ovary or Peritoneum,” Gynecol Oncol, 2008, 110(1):56-9. [PubMed 18457865]
  66. Ranganathan P, Armamento-Villareal R. Aromatase inhibitors and osteoporosis: comment on the review by Felson and Cummings. Arthritis Rheum. 2006;54(4):1355-1356. doi:10.1002/art.21741 [PubMed 16575867]
  67. Refer to manufacturer's labeling.
  68. Sestak I, Cuzick J, Sapunar F, et al. Risk factors for joint symptoms in patients enrolled in the ATAC trial: a retrospective, exploratory analysis. Lancet Oncol. 2008;9(9):866-872. doi:10.1016/S1470-2045(08)70182-7 [PubMed 18703382]
  69. Shulman DI, Francis GL, Palmert MR, et al. Use of aromatase inhibitors in children and adolescents with disorders of growth and adolescent development. Pediatrics. 2008;121(4):e975-983. [PubMed 18381525]
  70. Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. J Neurosci. 2006;26(21):5777-5785. doi:10.1523/JNEUROSCI.5223-05.2006 [PubMed 16723535]
  71. Teede HJ, Misso ML, Costello MF, et al; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018;110(3):364-379. doi: 10.1016/j.fertnstert.2018.05.004. [PubMed 30033227]
  72. Thurlimann B, Keshaviah A, Coates AS, et al; Breast International Group (BIG) 1-98 Collaborative Group. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer [published correction appears in N Engl J Med. 2006;354(20):2200]. N Engl J Med. 2005;353(26):2747-2757. doi:10.1056/NEJMoa052258 [PubMed 16382061]
  73. Tripathy D, Im SA, Colleoni M, et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor positive, advanced breast cancer (MONALEESA-7): a randomized phase 3 trial. Lancet Oncol. 2018;19(7):904-915. doi:10.1016/S1470-2045(18)30292-4 [PubMed 29804902]
  74. Tulandi T, Martin J, Al-Fadhli R, et al. Congenital malformations among 911 newborns conceived after infertility treatment with letrozole or clomiphene citrate. Fertil Steril. 2006;85(6):1761-1765. [PubMed 16650422]
  75. Turaka K, Nottage JM, Hammersmith KM, Nagra PK, Rapuano CJ. Dry eye syndrome in aromatase inhibitor users. Clin Exp Ophthalmol. 2013;41(3):239-243. doi:10.1111/j.1442-9071.2012.02865.x [PubMed 22957932]
  76. US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/default.html. Updated September 2016. Accessed October 5, 2016.
  77. van Staa TP, Leufkens HG, Abenhaim L, Zhang B, Cooper C. Oral corticosteroids and fracture risk: relationship to daily and cumulative doses. Rheumatology (Oxford). 2000;39(12):1383-1389. doi:10.1093/rheumatology/39.12.1383 [PubMed 11136882]
  78. Varimo T, Huopio H, Kariola L, et al. Letrozole versus testosterone for promotion of endogenous puberty in boys with constitutional delay of growth and puberty: a randomised controlled phase 3 trial. Lancet Child Adolesc Health. 2019;3(2):109-120. doi:10.1016/S2352-4642(18)30377-8 [PubMed 30612946]
  79. Waning DL, Guise TA. Cancer-associated muscle weakness: What's bone got to do with it? Bonekey Rep. 2015;4:691. doi:10.1038/bonekey.2015.59 [PubMed 25992285]
  80. Wickman S, Sipilä I, Ankarberg-Lindgren C, Norjavaara E, Dunkel L. A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled. Lancet. 2001;357:1743-1748. [PubMed 11403810]
  81. Zagouri F, Sergentanis TN, Azim HA Jr, et al. Aromatase inhibitors in male breast cancer: a pooled analysis. Breast Cancer Res Treat. 2015;151(1):141-147. doi:10.1007/s10549-015-3356-9 [PubMed 25850534]
  82. Zagouri F, Sergentanis TN, Koutoulidis V, et al. Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series. Br J Cancer. 2013;108(11):2259-2263. doi:10.1038/bjc.2013.255 [PubMed 23722469]
  83. Zaman K, Thürlimann B, Huober J, et al. Bone mineral density in breast cancer patients treated with adjuvant letrozole, tamoxifen, or sequences of letrozole and tamoxifen in the BIG 1-98 study (SAKK 21/07). Ann Oncol. 2012;23(6):1474-1481. doi:10.1093/annonc/mdr448 [PubMed 22003243]
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