Introduction
Faslodex (fulvestrant) is an estrogen receptor antagonist indicated for the treatment of hormone receptor-positive advanced breast cancer in postmenopausal women. As a selective estrogen receptor downregulator (SERD), it represents an important therapeutic option in endocrine therapy for metastatic breast cancer.
Mechanism of Action
Fulvestrant competitively binds to estrogen receptors with an affinity comparable to estradiol. Unlike selective estrogen receptor modulators (SERMs), fulvestrant lacks agonist activity and induces a conformational change that results in receptor degradation. This leads to complete estrogen receptor blockade and downregulation of cellular estrogen receptor protein levels, effectively inhibiting estrogen-mediated signaling pathways.
Indications
FDA-approved for:
- Treatment of hormone receptor-positive, HER2-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
- Treatment of hormone receptor-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy
- Combination therapy with palbociclib or abemaciclib for women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer with disease progression after endocrine therapy
Dosage and Administration
Standard dosing: 500 mg intramuscularly on days 1, 15, 29, and once monthly thereafter Administration: Administer as two 5 mL injections (250 mg each) slowly into the gluteal muscles Special populations:- Renal impairment: No dosage adjustment necessary for mild to moderate impairment
- Hepatic impairment: Use with caution in moderate to severe impairment
- Elderly: No dosage adjustment required
Pharmacokinetics
Absorption: Slowly absorbed following IM administration with peak concentrations reached in approximately 7 days Distribution: Volume of distribution ~3-5 L/kg; highly bound to plasma proteins (99%) Metabolism: Extensive hepatic metabolism via multiple pathways similar to endogenous steroids Elimination: Primarily fecal excretion (≈90%); terminal half-life approximately 40 days Steady-state: Achieved after 3-6 months of monthly administrationContraindications
- Known hypersensitivity to fulvestrant or any component of the formulation
- Pregnancy or women of childbearing potential
- Patients with bleeding diatheses or thrombocytopenia
- Patients receiving anticoagulant therapy (relative contraindication due to IM administration)
Warnings and Precautions
Injection site reactions: May include pain, inflammation, and rarely, sterile abscess formation Hepatic impairment: Use with caution in patients with moderate to severe hepatic impairment Coagulation disorders: Caution required in patients with bleeding diatheses or thrombocytopenia Embryo-fetal toxicity: Can cause fetal harm; pregnancy must be excluded before initiation Concurrent anticoagulants: Increased risk of bleeding with IM administrationDrug Interactions
Strong CYP3A4 inducers: (e.g., rifampin, carbamazepine) may decrease fulvestrant concentrations Anticoagulants: (e.g., warfarin, direct oral anticoagulants) may increase bleeding risk due to IM administration No clinically significant interactions with tamoxifen or aromatase inhibitorsAdverse Effects
Very common (≥10%):- Injection site reactions (pain, inflammation) (34%)
- Nausea (26%)
- Fatigue (19%)
- Hot flashes (18%)
- Arthralgia (15%)
- Headache (15%)
- vomiting, diarrhea, constipation
- back pain, bone pain
- dyspnea, pharyngitis
- rash, sweating
- urinary tract infections
- Hepatic enzyme elevations (2%)
- Thromboembolic events (1%)
- Severe injection reactions including sterile abscess
Monitoring Parameters
Baseline:- Pregnancy test in women of childbearing potential
- Liver function tests
- Complete blood count
- Assessment of coagulation parameters if indicated
- Injection sites for reactions
- Symptoms of thromboembolism
- Liver function periodically
- Disease response assessment per standard guidelines
- Bone health monitoring (especially with combination CDK4/6 inhibitors)
Patient Education
- This medication requires monthly intramuscular injections administered by healthcare professionals
- Report any signs of injection site problems: increasing pain, redness, swelling, or drainage
- Notify your healthcare provider if you experience unusual bleeding or bruising
- Use effective contraception during treatment and for 1 year after discontinuation
- Report symptoms of blood clots: sudden shortness of breath, chest pain, leg pain or swelling
- Maintain regular follow-up appointments for monitoring
- Inform all healthcare providers about your Faslodex treatment
References
1. FDA Prescribing Information: Fulvestrant (Faslodex) 2. Robertson JFR, et al. Fulvestrant 500 mg versus anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON): overall survival results. Lancet Oncol. 2021;22(10):1409-1418 3. Di Leo A, et al. Final overall survival: fulvestrant 500 mg vs 250 mg in the randomized CONFIRM trial. J Natl Cancer Inst. 2014;106(1):djt337 4. National Comprehensive Cancer Network (NCCN) Guidelines: Breast Cancer Version 3.2023 5. Howell A, et al. Fulvestrant versus anastrozole for the treatment of advanced breast cancer in postmenopausal women: prospective follow-up of the 'FACT' trial. Breast Cancer Res Treat. 2017;163(3):489-494 6. Cardoso F, et al. 5th ESO-ESMO international consensus guidelines for advanced breast cancer (ABC 5). Ann Oncol. 2020;31(12):1623-1649
This information is intended for educational purposes and should not replace professional medical advice. Always consult with a qualified healthcare provider for personalized medical recommendations.