FEMARA

Absorption and Distribution: Letrozole is rapidly and completely absorbed from the gastrointestinal tract and absorption is not affected by food. It is metabolized slowly to an inactive metabolite whose glucuronide conjugate is excreted renally, representing the major clearance pathway. About 90% of radiolabeled letrozole is recovered in urine. Letrozole’s terminal elimination half-life is about 2 days and steady-state plasma concentration after daily 2.5 mg dosing is reached in 2-6 weeks. Plasm...

Figure 1: Disease-Free Survival (Median follow-up 73 months, ITT Approach) Femara fig2 Femara fig 3 Femara fig 4 Femara Fig 5 14.1 Updated Adjuvant Treatment of Early Breast Cancer In a multicenter study (BIG 1-98, NCT00004205) enrolling over 8,000 postmenopausal women with resected, receptor-positive early breast cancer, one of the following treatments was randomized in a double-blind manner: Option 1: Tamoxifen for 5 years Femara for 5 years Tamoxifen for 2 years followed by Femara for 3 years Femara for 2 years followed by tamoxifen for 3 years Option 2: A. Tamoxifen for 5 years B. Femara f...

The following adverse reactions are discussed in greater detail in other sections of the labeling. Bone effects [see Warnings and Precautions (5.1)] Increases in cholesterol [see Warnings and Precautions (5.2)] Fatigue and Dizziness [see Warnings and Precautions (5.4)] The most common adverse reactions (greater than 20%) were hot flashes, arthralgia; flushing, asthenia, edema, arthralgia, headache, dizziness, hypercholesterolemia, sweating increased, bone pain; and musculoskeletal. ( 6 ) To repo...

Pregnancy: Letrozole can cause fetal harm [see Use in Specific Populations (8.1)] . Known hypersensitivity to the active substance, or to any of the excipients [see Adverse Reactions (6)] . Pregnancy. ( 4 ) Known hypersensitivity to the active substance, or to any of the excipients. ( 4 )

Decreases in bone mineral density may occur. Consider bone mineral density monitoring. ( 5.1 ) Increases in total cholesterol may occur. Consider cholesterol monitoring. ( 5.2 ) Fatigue, dizziness, and somnolence may occur. Exercise caution when operating machinery. ( 5.4 ) Embryo-Fetal Toxicity: Can cause fetal harm when administered to pregnant women. Obtain a pregnancy test in females of reproductive potential. Advise females of reproductive potential to use effective contraception. ( 5.6 , 8...

7 DRUG INTERACTIONS Tamoxifen Coadministration of Femara and tamoxifen 20 mg daily resulted in a reduction of letrozole plasma levels of 38% on average (Study P015). Clinical experience in the second-line breast cancer trials (AR/BC2 and AR/BC3) indicates that the therapeutic effect of Femara therapy is not impaired if Femara is administered immediately after tamoxifen. Cimetidine A pharmacokineti...