Dosing and uses of Faslodex (fulvestrant)
Adult dosage forms and strengths
injectable solution
- 50mg/mL
Breast Cancer
Monotherapy
- Indicated for hormone receptor (HR) positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy
- 500 mg IM on days 1, 15, 29, then once monthly thereafter
Combination with palbocicliB
- Indicated for HR-positive, (HER2)-negative advanced or metastatic breast cancer in combination with palbociclib in women (regardless of menopausal status) with disease progression after endocrine therapy
- Fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter
- Palbociclib starting dose: 125 mg PO qDay with food x21 days followed by 7 days off therapy to comprise a complete cycle of 28 days
- Pre/perimenopausal women treated with the palbociclib combination should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards
Dosage modifications
Hepatic impairment
- Moderate hepatic impairment (Child-Pugh class B): 250 mg IM on days 1, 15, 29, then once monthly thereafter
- Severe impairment: Not studied
Pediatric dosage forms and strengths
injectable solution
- 50mg/mL
Precocious Puberty (Off-label)
Indicated in females for progressive precocious puberty associated with McCune-Albright syndrome
4 mg/kg IM qMonth
Hepatic Impairment
- Dose adjustment may be required, although no specific recommendations defined for children with hepatic impairment (in adults with Child-Pugh class B, the dose is decreased by 50%)
Faslodex (fulvestrant) adverse (side) effects
>10%
Nausea (26%)
Asthenia (23%)
Pain (19%)
Vasodilatation (18%)
Pharyngitis (16%)
HA (15%)
Back pain (14%)
Constipation (13%)
Vomiting (13%)
Abd pain (12%)
Diarrhea (12%)
Inj site pain (11%)
1-10%
Cough (10%)
Anorexia (9%)
Peripheral edema (9%)
Chest pain (7%)
Flu-like syndrome (7%)
Rash (7%)
Depression (6%)
Fever (6%)
UTI (6%)
Anemia (5%)
<1%
Angioedema
Leukopenia
Myalgia
Thrombosis
Osteoporosis
Postmarketing Reports
Injection site reaction
Thromboembolic phenomena
Myalgia
Vertigo
Leukopenia
Hypersensitivity reactions including angioedema and urticaria
Vaginal bleeding (mainly during the first 6 weeks after changing from existing hormonal therapy)
Elevated bilirubin, gamma GT, hepatitis, and liver failure
Warnings
Contraindications
Hypersensitivity to fulvestrant or any component of formulation
Cautions
Caution in bleeding diathesis, thrombocytopenia, therapeutic anticoagulation
Hepatic impairment; decrease dose to 250 mg dose with moderate hepatic impairment (Child-Pugh class B)
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception; see Pregnancy section
Therapy can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels
Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy reported; caution should be taken while administering therapy at dorsogluteal injection site due to proximity of underlying sciatic nerve
Pregnancy and lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman
In animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis resulted in embryo-fetal toxicity at daily doses that are significantly less than the maximum recommended human dose
Advise pregnant women of the potential risk to a fetus
Advise females of reproductive potential to use effective contraception during treatment and for 1 year after the last dose
Lactation
Excretion in human milk unknown; do not breastfeed
Pregnancy category: d
Lactation: excretion in milk unknown; contraindicated
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Faslodex (fulvestrant)
Mechanism of action
Breast cancer: Competitively binds to estrogen receptors on tumors and other tissue targets, producing nuclear complex that decreases DNA synthesis and inhibits estrogen effects; no estrogen-receptor agonist activity; downregulates estrogen receptors and inhibits breast tumor growth
Precocious puberty (off-label): Estrogen receptor antagonist
Absorption
Peak Plasma Time: 7 days
Duration: Plasma levels detected for 1 month
Distribution
Protein Bound: 99%
Vd: 3-5 L/kg
Metabolism
Via multiple hepatic pathways
Excretion
Half-Life: 40 days
Excretion: Feces >90%; urine <1%
Administration
IM Administration
Administer IM in buttocks slowly (over 1-2 minutes per injection) as two 5-mL (250 mg) injections, on in each buttock (or one 5-mL IM injection for moderate hepatic impairment)
