Fulvestrant 250 mg/5 ml

INDICATIONS

Fulvestrant is an estrogen receptor antagonist 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.
HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. ... Read moreFulvestrant is an estrogen receptor antagonist 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.
HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy.
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.

PHARMACOLOGY

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. In in vivo studies in immature rats and ovariectomized monkeys, fulvestrant blocked the uterotrophic action of estradiol. In postmenopausal women, the absence of changes in plasma concentrations of FSH and LH in response to fulvestrant treatment (250 mg monthly) suggests no peripheral steroidal effects.

DOSAGE & ADMINISTRATION

Fulvestrant 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.Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

INTERACTION

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

SIDE EFFECTS

The most common adverse reactions occurring in ≥5% of patients receiving fulvestrant 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 fulvestrant patients and were not dose-dependent.

PREGNANCY & LACTATION

There are no available data in pregnant women to inform the drug-associated risk. There is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant.

PRECAUTIONS & WARNINGS

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 Fulvestrant 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: Fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.

THERAPEUTIC CLASS

Cytotoxic Chemotherapy

STORAGE CONDITIONS

Refrigerate 2°-8°C. To protect from light, store in the original carton until the time of use.