Is taking 2.5 mg of Femara (letrozole) every other day as effective as taking it daily?

Femara (Letrozole) Every Other Day Dosing

No, taking 2.5 mg of Femara every other day is not as effective as daily dosing and should only be used in patients with severe hepatic impairment or cirrhosis. 1

Standard Dosing Recommendation

• The FDA-approved dose of letrozole is 2.5 mg once daily without regard to meals. 1
• Daily dosing is required to maintain consistent aromatase inhibition and estrogen suppression throughout treatment. 2, 3
• Clinical trials demonstrating letrozole's efficacy in breast cancer used the 2.5 mg daily dose, not intermittent dosing. 2, 4, 5

Pharmacokinetic Rationale Against Every-Other-Day Dosing

• Letrozole has a terminal half-life that increases by approximately 42% at steady state compared to single-dose kinetics, reaching steady state with daily dosing. 6
• The drug achieves over 98% peripheral aromatase inhibition and suppresses blood and urinary estrogen levels by over 95% after 2 weeks of daily treatment. 3
• Interrupting daily dosing would compromise the sustained estrogen suppression necessary for therapeutic efficacy. 3, 6
• At steady state with daily dosing, approximately 70% of the administered dose is excreted in urine, with only 6% as unchanged drug, indicating the importance of continuous daily administration for maintaining therapeutic levels. 6

The Only Exception: Hepatic Impairment

• Patients with cirrhosis or severe hepatic impairment should receive 2.5 mg every other day. 1
• This is the only FDA-approved indication for alternate-day dosing and reflects reduced drug clearance in severe liver disease. 1

Clinical Efficacy Data

• All pivotal trials showing letrozole's superiority over tamoxifen in adjuvant therapy, extended adjuvant therapy, and advanced breast cancer used daily 2.5 mg dosing. 2, 4, 5
• Letrozole 2.5 mg daily achieved objective response rates of 19.5-23.6% with median response durations of 24-33 months in advanced disease. 3
• No clinical trial data support the efficacy of every-other-day dosing in patients without severe hepatic impairment. 2, 3, 4

Common Pitfall to Avoid

• Do not reduce dosing frequency to minimize side effects without medical justification, as this compromises treatment efficacy. 2, 3
• If tolerability is a concern, address specific adverse events (hot flushes, arthralgia, myalgia) with supportive measures rather than altering the dosing schedule. 2, 5
• Patients should continue 2.5 mg daily unless they have documented cirrhosis or severe hepatic impairment requiring dose modification. 1