h letrozole is unknown. The planned duration of treatment in the study was 5 years with 73% of the patients having completed adjuvant therapy. Treatment should be discontinued at relapse [see Clinical Studies (14.1)].
2.3 Use in Extended Adjuvant Treatment of Early Breast CancerIn the extended adjuvant setting, the optimal treatment duration with Femara is not known. The planned duration of treatment in the study was 5 years. In the final updated analysis, conducted at a median follow-up of 62 months, the median treatment duration was 60 months. Seventy-one percent of patients were treated for at least 3 years and 58% of patients completed at least 4.5 years of extended adjuvant treatment. The treatment should be discontinued at tumor relapse [see Clinical Studies (14.2)].
2.4 Use in First and Second-Line Treatment of Advanced Breast CancerIn patients with advanced disease, treatment with Femara should continue until tumor progression is evident [see Clinical Studies (14.4, 14.5)].
2.5 Use in Hepatic ImpairmentNo dosage adjustment is recommended for patients with mild to moderate hepatic impairment, although Femara blood concentrations were modestly increased in subjects with moderate hepatic impairment due to cirrhosis. The dose of Femara in patients with cirrhosis and severe hepatic dysfunction should be reduced by 50% [see Warnings and Precautions (5.3)]. The recommended dose of Femara for such patients is 2.5 mg administered every other day. The effect of hepatic impairment on Femara exposure in noncirrhotic cancer patients with elevated bilirubin levels has not been determined.
2.6 Use in Renal ImpairmentNo dosage adjustment is required for patients with renal impairment if creatinine clearance is ≥10 mL/min [see Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
2.5 mg tablets: dark yellow, film-coated, round, slightly biconvex, with beveled edges (imprinted with the letters FV on one side and CG on the other side).
4 CONTRAINDICATIONS
Femara may cause fetal harm when administered to a pregnant woman and the clinical benefit to premenopausal women with breast cancer has not been demonstrated. Femara is contraindicated in women who are or may become pregnant. If Femara is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)].
5 WARNINGS AND PRECAUTIONS
5.1 Bone EffectsUse of Femara may cause decreases in bone mineral density (BMD). Consideration should be given to monitoring BMD. Results of a substudy to eva luate safety in the adjuvant setting comparing the effect on lumbar spine (L2-L4) bone mineral density (BMD) of adjuvant treatment with letrozole to that with tamoxifen showed at 24 months a median decrease in lumbar spine BMD of 4.1% in the letrozole arm compared to a median increase of 0.3% in the tamoxifen arm (difference = 4.4%) (P<0.0001) [see Adverse reactions (6.1)]. Updated results from the BMD substudy in the extended adjuvant setting demonstrated that at 2 years patients receiving letrozole had a median decrease from baseline of 3.8% in hip BMD compared to a median decrease of 2.0% in the placebo group. The changes from baseline in lumbar spine BMD in letrozole and pla |
