Fulvestrant is an estrogen receptor antagonist used for the treatment of certain types of advanced breast cancer. It is indicated for:

• Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women who have not previously received endocrine therapy.
• HR-positive advanced breast cancer in postmenopausal women whose disease has progressed after previous endocrine therapy.
• HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women when used together with Ribociclib as the initial endocrine-based treatment or after disease progression on endocrine therapy.
• HR-positive, HER2-negative advanced or metastatic breast cancer in combination with Palbociclib or Abemaciclib in women whose cancer has progressed following endocrine therapy.

Many breast cancers contain estrogen receptors (ER), and estrogen can stimulate the growth of these tumors. Fulvestrant works as an estrogen receptor antagonist that competitively binds to estrogen receptors with an affinity similar to estradiol. After binding, it reduces and degrades the estrogen receptor protein in breast cancer cells, thereby inhibiting tumor growth.

Laboratory (in-vitro) studies have shown that fulvestrant can inhibit the growth of both tamoxifen-resistant and estrogen-sensitive human breast cancer cell lines (MCF-7). In animal studies, fulvestrant delayed the formation of tumors from human breast cancer xenografts and inhibited the growth of established tumors, including those resistant to tamoxifen.

Unlike some hormonal agents, fulvestrant does not show estrogen-like stimulating effects in uterine tissue during animal studies. It also blocks the uterine-stimulating action of estradiol. In postmenopausal women receiving fulvestrant (250 mg monthly), there were no significant changes in plasma levels of FSH and LH, suggesting that the drug has no peripheral steroid-like hormonal effects.

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.

Fulvestrant currently has no significant known drug–drug interactions. Although fulvestrant is metabolized in laboratory studies by the enzyme CYP3A4, clinical interaction studies with drugs such as Ketoconazole (a CYP3A4 inhibitor) and Rifampin (a CYP3A4 inducer) did not significantly affect fulvestrant pharmacokinetics. Therefore, dose adjustment is generally not required when fulvestrant is used together with CYP3A4 inhibitors or inducers.

The most commonly reported adverse reactions occurring in ≥5% of patients receiving fulvestrant 500 mg include injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremities, hot flush, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation.

Elevations in hepatic enzymes (ALT, AST, ALP) were observed in more than 15% of patients treated with fulvestrant and were not related to dose.

There is no adequate data available regarding the use of fulvestrant in pregnant women to determine the associated risks. It is also unknown whether fulvestrant passes into human breast milk, affects milk production, or harms a breastfed infant.

• Risk of Bleeding: Use carefully in patients with bleeding disorders, low platelet count, or those taking anticoagulant medicines.
• Hepatic Impairment: Patients with moderate liver impairment should receive a reduced dose of 250 mg.
• Injection Site Reaction: Administer carefully at the dorsogluteal injection site due to the nearby sciatic nerve.
• Embryo-Fetal Toxicity: Fulvestrant may cause harm to a developing fetus. Women of reproductive potential should use effective contraception during treatment.
• Estradiol Test Interference: Fulvestrant may interfere with laboratory immunoassays used to measure serum estradiol, leading to falsely elevated results.

Information about fulvestrant overdose in humans is limited. A few cases of overdose have been reported, but no serious adverse effects were observed in healthy volunteers who received high intravenous doses producing plasma levels 10–15 times higher than those seen after intramuscular injection.

The potential toxicity at these or higher levels in cancer patients with other medical conditions remains unclear. There is no specific antidote for fulvestrant overdose. In case of overdose, treatment should focus on supportive care and symptomatic management.

Cytotoxic Chemotherapy

Store in a refrigerator at 2°C–8°C. Keep the medicine in its original carton to protect it from light until it is ready for use.