Femara (letrozole) is a nonsteroidal aromatase inhibitor indicated for the adjuvant treatment of hormone receptor-positive early breast cancer in postmenopausal women. It represents a cornerstone in endocrine therapy, specifically designed to suppress estrogen production—a key driver in hormone-sensitive malignancies. By targeting the aromatase enzyme system, Femara demonstrates superior efficacy in reducing recurrence risk and improving disease-free survival compared to earlier therapeutic options. Its well-characterized pharmacokinetic profile and oral administration make it a preferred choice among oncologists for long-term management strategies.

Features

• Contains 2.5 mg letrozole per film-coated tablet
• Nonsteroidal aromatase inhibitor class medication
• High specificity for cytochrome P450 aromatase enzyme
• Oral administration with once-daily dosing
• Bioavailability of 99.9% with food-independent absorption
• Mean elimination half-life of approximately 2 days
• Hepatic metabolism via CYP3A4 and CYP2A6 isoenzymes
• Renal excretion as inactive glucuronide metabolites

Benefits

• Significantly reduces risk of cancer recurrence in hormone-sensitive early breast cancer
• Demonstrates superior efficacy compared to tamoxifen in postmenopausal women
• Improves disease-free survival rates across all patient subgroups
• Red contralateral breast cancer incidence by approximately 40%
• Well-tolerated profile enables long-term adjuvant therapy adherence
• Oral administration facilitates outpatient management and quality of life

Common use

Femara is primarily prescribed as extended adjuvant treatment following standard tamoxifen therapy completion in postmenopausal women with hormone receptor-positive early breast cancer. It is also indicated as first-line treatment for advanced breast cancer in this population. Clinical practice increasingly utilizes Femara in neoadjuvant settings to reduce tumor size before surgery. Off-label applications include ovulation induction in fertility treatments, though this requires careful specialist supervision due to differing dosing protocols and monitoring requirements.

Dosage and direction

The recommended dosage is one 2.5 mg tablet administered orally once daily, with or without food. Treatment duration typically continues for five years based on individual risk assessment, though extended therapy may be considered for higher-risk patients. Tablets should be swallowed whole with water and administered at approximately the same time each day to maintain steady-state concentrations. No initial dosage adjustment is required for elderly patients or those with mild-to-moderate hepatic impairment. For patients with creatinine clearance <30 mL/min, careful monitoring is advised though formal dosage adjustment is not routinely recommended.

Precautions

Regular monitoring of bone mineral density is essential due to accelerated bone loss associated with estrogen suppression. Baseline DEXA scanning with follow-up assessments every 1-2 years is recommended, with concomitant calcium/vitamin D supplementation and consideration of bisphosphonate therapy. Liver function tests should be performed periodically, particularly in patients with pre-existing hepatic impairment. Cardiovascular risk assessment is advised given potential lipid profile alterations. Patients should be monitored for emerging cognitive changes or mood disturbances. Ophthalmologic examinations are recommended for patients reporting visual changes.

Contraindications

Femara is contraindicated in premenopausal women, pregnant patients, and those with known hypersensitivity to letrozole or any excipients in the formulation. It must not be administered concurrently with estrogen-containing therapies or other endocrine agents except in specifically validated sequencing protocols. Patients with severe hepatic impairment (Child-Pugh Class C) should avoid use due to insufficient safety data. Concomitant use with drugs that strongly induce CYP3A4 may significantly reduce letrozole concentrations and efficacy.

Possible side effects

• Very common (≥10%): Hot flashes (27%), arthralgia (21%), fatigue (16%), headache (14%), hypercholesterolemia (16%)
• Common (1-10%): Night sweats, weight increase, nausea, osteoporosis, fractures, hypertension, depression, dizziness
• Uncommon (0.1-1%): Thromboembolic events, cerebrovascular accident, endometrial hyperplasia, vaginal bleeding
• Rare (<0.1%): Hepatitis, anaphylactoid reactions, Stevens-Johnson syndrome
• Post-marketing reports: Palpitations, tachycardia, peripheral neuropathy, memory impairment

Drug interaction

Strong CYP3A4 inducers (rifampicin, phenytoin, carbamazepine, St. John’s wort) may significantly decrease letrozole plasma concentrations. CYP2A6 inhibitors may potentially increase exposure, though clinical significance remains uncertain. Tamoxifen co-administration reduces letrozole plasma concentrations by 38% and is not recommended. No clinically significant interactions observed with warfarin, cimetidine, or commonly used antihypertensive agents. Caution advised with other medications that prolong QT interval.

Missed dose

If a dose is missed, patients should take it as soon as remembered unless less than 12 hours remain until the next scheduled dose. In such cases, the missed dose should be skipped and the regular dosing schedule resumed. Doubling doses to compensate for missed administration is not recommended. Consistent timing maintenance is important for optimal therapeutic effect, though minor variations (within 4 hours) are not clinically significant given the drug’s long half-life.

Overdose

No specific antidote exists for letrozole overdose. Reported cases of intentional overdose (up to 62.5 mg single dose) demonstrated no severe adverse events. General supportive measures should be instituted with monitoring of vital signs. Gastrointestinal decontamination may be considered if ingestion occurred within 2 hours. Hemodialysis is unlikely to be beneficial due to high protein binding and extensive tissue distribution. Symptomatic management should address any clinical manifestations, particularly focusing on cardiovascular stability.

Storage

Store at room temperature (15-30°C/59-86°F) in original packaging to protect from light and moisture. Keep blister strips intact until immediate use to maintain stability. Do not store in bathroom areas where humidity fluctuations may occur. Keep out of reach of children and pets. Do not use beyond the expiration date printed on packaging. Proper disposal of unused medication through take-back programs is recommended to prevent environmental contamination.

Disclaimer

This information does not replace professional medical advice. Treatment decisions must be made by qualified healthcare providers based on individual patient characteristics and current clinical guidelines. Dosage and administration may vary based on specific clinical circumstances. Patients should report any adverse effects to their healthcare provider and never adjust dosage without medical supervision. The full prescribing information contains complete details on warnings, precautions, and adverse reactions.

Reviews

Clinical trials demonstrate consistent efficacy across multiple large-scale studies. The BIG 1-98 trial (N=8,028) showed Femara significantly improved disease-free survival compared to tamoxifen (HR 0.82; p=0.007) with particular benefit in reducing distant metastases. The MA-17 trial confirmed extended adjuvant therapy reduced recurrence risk by 42% versus placebo. Real-world evidence supports maintained efficacy in diverse populations, though individual responses may vary based on tumor biology and compliance. Most clinicians report favorable risk-benefit profiles, noting manageable side effects that typically don’t require therapy discontinuation.