. Clinical experience in the second-line breast cancer trials indicates that the therapeutic effect of Femara therapy is not impaired if Femara is administered immediately after tamoxifen.
Cimetidine
A pharmacokinetic interaction study with cimetidine showed no clinically significant effect on letrozole pharmacokinetics.
Warfarin
An interaction study with warfarin showed no clinically significant effect of letrozole on warfarin pharmacokinetics.
Other anticancer agents
There is no clinical experience to date on the use of Femara in combination with other anticancer agents.
8 USE IN SPECIFIC POPULATIONS
8.1 PregnancyPregnancy Category X [see Contraindications (4)]. 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 this drug 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.
Femara caused adverse pregnancy outcomes, including congenital malformations, in rats and rabbits at doses much smaller than the daily maximum recommended human dose (MRHD) on a mg/m2 basis. Effects included increased post-implantation pregnancy loss and resorptions, fewer live fetuses, and fetal malformations affecting the renal and skeletal systems. Animal data and letrozole’s mechanism of action raise concerns that letrozole could be a human teratogen as well.
Reproduction studies in rats showed embryo and fetal toxicity at letrozole doses during organogenesis equal to or greater than 1/100 the daily maximum recommended human dose (MHRD) (mg/m2 basis). Adverse effects included: intrauterine mortality; increased resorptions and postimplantation loss; decreased numbers of live fetuses; and fetal anomalies including absence and shortening of renal papilla, dilation of ureter, edema and incomplete ossification of frontal skull and metatarsals. Letrozole doses 1/10 the daily MHRD (mg/m2 basis) caused fetal domed head and cervical/centrum vertebral fusion. In rabbits, letrozole caused embryo and fetal toxicity at doses about 1/100,000 and 1/10,000 the daily MHRD respectively (mg/m2 basis). Fetal anomalies included incomplete ossification of the skull, sternebrae, and fore- and hind legs [see Nonclinical Toxicology (13.2)].
Physicians should discuss the need for adequate contraception with women who are recently menopausal. Contraception should be used until postmenopausal status is clinically well established.
8.3 Nursing MothersIt is not known if letrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from letrozole, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric UseThe safety and effectiveness in pediatric patients have not been established.
8.5 Geriatric UseThe median age of patients in all studies of first-line and second-line treatment of metastatic breast cancer was 64-65 years. About 1/3 of the patients were ≥70 years old. In the first-line study, patients ≥70 years of age experience |
