Fulvestrant

Monotherapy FASLODEX is indicated for the treatment of: • Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or • HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy FASLODEX is indicated for the treatment of: • HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. • HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy.

Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines. In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts. Fulvestrant showed no agonist-type effects in in vivo uterotrophic assays in immature or ovariectomized mice and rats.

• FASLODEX 500 mg should be administered intramuscularly into the buttocks (gluteal area) slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on Days 1, 15, 29, and once monthly thereafter. • A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock (gluteal area) slowly (1 - 2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter.

FASLODEX is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with FASLODEX. • Hypersensitivity.

• Risk of Bleeding: Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. • Increased Exposure in Patients with Hepatic Impairment: Use a 250 mg dose for patients with moderate hepatic impairment. • Injection Site Reaction: Use caution while administering FASLODEX at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. • Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. • Immunoassay Measurement of Serum Estradiol: FASLODEX can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.

The following adverse reactions are discussed in more detail in other sections of the labeling: • Risk of Bleeding • Increased Exposure in Patients with Hepatic Impairment • Injection Site Reaction • Embryo-Fetal Toxicity • The most common adverse reactions occurring in ≥5% of patients receiving FASLODEX 500 mg were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation. • Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of FASLODEX patients and were not dose-dependent.

There are no known drug-drug interactions. Although, fulvestrant is metabolized by CYP 3A4 in vitro, drug interactions studies with ketoconazole or rifampin did not alter fulvestrant pharmacokinetics. Dose adjustment is not needed in patients co-prescribed CYP 3A4 inhibitors or inducers. • There are no known drug-drug interactions.

REFRIGERATE, 2°-8°C (36°-46°F). TO PROTECT FROM LIGHT, STORE IN THE ORIGINAL CARTON UNTIL TIME OF USE.