Fulvestrant

Fulvestrant is primarily indicated for the treatment of hormone receptor-positive (HR+) advanced or metastatic breast cancer in postmenopausal women.

Approved Indications:

• Advanced Breast Cancer: For postmenopausal women with HR+ metastatic breast cancer whose disease has progressed following anti-estrogen therapy (e.g., tamoxifen or aromatase inhibitors).
• Combination Therapy: Can be used in combination with CDK4/6 inhibitors (e.g., palbociclib, ribociclib, abemaciclib) for HR+, HER2-negative advanced or metastatic breast cancer in women who have received prior endocrine therapy.

Off-label / Clinically Accepted Uses:

• Neoadjuvant Therapy: Occasionally considered in selected cases of locally advanced HR+ breast cancer for tumor reduction prior to surgery.
• Endocrine-Resistant Breast Cancer: Used in cases where resistance to other anti-estrogen therapies has developed.

Adults:

• Standard Dose: 500 mg administered intramuscularly (IM) once every 28 days.
• Loading Dose: On initiation, 500 mg IM on day 0, followed by 500 mg IM on day 14, then every 28 days thereafter.

Pediatrics:

• Safety and efficacy in pediatric populations have not been established; use is not recommended.

Special Populations:

• Hepatic Impairment: No dose adjustment required in mild to moderate impairment; use with caution in severe hepatic impairment.
• Renal Impairment: No dose adjustment recommended; monitor for tolerability.
• Elderly: Dose adjustments not necessary; standard dosing applies.

Administration Route:

• Intramuscular injection, preferably alternating between gluteal muscles.

Fulvestrant is a selective estrogen receptor degrader (SERD). It binds competitively to estrogen receptors (ERs) on breast cancer cells, blocking estrogen-mediated transcriptional activity. Upon binding, fulvestrant accelerates proteasomal degradation of the ER, leading to downregulation of ER expression. This dual action—receptor blockade and degradation—reduces tumor cell proliferation in HR+ breast cancer.

• Absorption: Slowly absorbed after IM injection; peak plasma concentrations occur approximately 4–6 days post-injection.
• Distribution: Highly protein-bound (~99%) and widely distributed in body tissues.
• Metabolism: Primarily metabolized in the liver via CYP3A4-mediated pathways.
• Half-life: Terminal half-life approximately 40 days.
• Excretion: Mainly fecal (~90%), minor renal elimination.
• Onset of Action: Therapeutic effects are gradual; clinical responses typically observed after 1–2 months.

• Pregnancy: Animal studies indicate potential teratogenicity; human data are limited. Use during pregnancy is contraindicated unless the potential benefit outweighs risk.
• Lactation: Unknown if excreted in human milk; breastfeeding is not recommended during treatment.
• Caution: Women of childbearing potential should use effective contraception during treatment and for 3 months after the last dose.

• Primary Class: Antiestrogen / Hormonal therapy
• Subclass: Selective Estrogen Receptor Degrader (SERD)

• Known hypersensitivity to fulvestrant or any excipients in the formulation.
• Pregnancy due to potential teratogenic effects.
• Severe uncontrolled liver disease.

• Hepatic Impairment: Monitor liver function tests periodically.
• Injection Site Reactions: May cause pain, swelling, or erythema; rotate injection sites.
• Thromboembolic Events: Monitor in patients with a history of venous thromboembolism.
• Bone Health: Long-term estrogen deprivation may increase risk of osteoporosis; monitor bone density in at-risk patients.

Common:

• Hot flashes
• Injection site reactions
• Nausea, vomiting
• Fatigue, asthenia
• Headache

Serious / Rare:

• Hepatic enzyme elevations
• Thromboembolic events (DVT, PE)
• Severe hypersensitivity reactions
• Rare cases of osteoporosis-related fractures

Timing & Severity:

• Side effects may occur within the first few weeks; injection site reactions usually mild and self-limiting.

• CYP3A4 Inducers (e.g., rifampicin, carbamazepine): May reduce fulvestrant plasma concentrations, potentially decreasing efficacy.
• CYP3A4 Inhibitors (e.g., ketoconazole): Can increase fulvestrant exposure; monitor for adverse effects.
• Other Hormonal Therapies: Concomitant use with estrogen-containing products may reduce therapeutic effectiveness.

• Updated guidelines recommend fulvestrant as standard therapy for postmenopausal women with HR+, HER2-negative advanced breast cancer following progression on aromatase inhibitors.
• Combination therapy with CDK4/6 inhibitors is now a standard first- or second-line option for endocrine-resistant disease.
• Emphasis on alternating gluteal IM injections to reduce local site reactions.

• Store at 2°C to 8°C (refrigerated).
• Protect from light; do not freeze.
• Keep in original packaging until use.
• Bring to room temperature before administration; do not shake vigorously.