(fool VES trant)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Faslodex: 250 mg/5 mL (5 mL) [contains alcohol, usp, benzyl alcohol, benzyl benzoate]
Brand Names: U.S.
- Antineoplastic Agent, Estrogen Receptor Antagonist
Estrogen receptor antagonist; competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that causes a dose-related down-regulation of estrogen receptors and inhibits tumor growth.
Vd: ~3 to 5 L/kg
Hepatic via multiple biotransformation pathways (CYP3A4 substrate involved in oxidation pathway, although relative contribution to metabolism unknown); metabolites formed are either less active or have similar activity to parent compound
Feces (~90%); urine (<1%)
Clearance: Children 1 to 8 years (based on a 4 mg/kg dose): Decreased by 32% compared to adults
Duration of Action
IM: Steady state concentrations reached within first month, when administered with additional dose given 2 weeks following the initial dose; plasma levels maintained for at least 1 month
Children 1 to 10 years: 70.4 ± 8.1 days
Adults 250 mg: ~40 days
99%; to plasma proteins (VLDL, LDL and HDL lipoprotein fractions)
Special Populations: Hepatic Function Impairment
In moderate hepatic impairment (Child-Pugh class B), the average AUC of fulvestrant increased by 70% compared with patients with normal hepatic function.
Use: Labeled Indications
Breast cancer, metastatic: Treatment of hormone-receptor (HR)-positive metastatic breast cancer (as monotherapy) in postmenopausal women with disease progression following antiestrogen therapy
Breast cancer, advanced or metastatic (second-line endocrine-based combination therapy): Treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer (in combination with palbociclib) in women with disease progression following endocrine therapy
Known hypersensitivity to fulvestrant or any component of the formulation
Breast cancer, metastatic (postmenopausal women): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly. In studies, the 500 mg once monthly dose was administered at 28 days ± 3 days (Di Leo 2014).
Breast cancer, advanced or metastatic (second-line endocrine-based combination therapy): Adult females (HER-2 negative): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days. Administer in combination with palbociclib (and an LHRH agonist [eg, goserelin] if pre- or perimenopausal); continue until disease progression or unacceptable toxicity (Turner 2015). Note: Refer to Palbociclib monograph for dosing in combination with fulvestrant.
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, renal elimination of fulvestrant is negligible.
Dosing: Hepatic Impairment
Mild impairment (Child-Pugh class A): No dosage adjustment is necessary.
Moderate impairment (Child-Pugh class B): Reduce initial doses and maintenance dose to 250 mg.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (use has not been evaluated).
For IM administration only. Administer 500 mg dose as two 5 mL IM injections (one in each buttocks) slowly over 1 to 2 minutes per injection.
Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Store in original carton at 2°C to 8°C (36°F to 46°F). Protect from light.
There are no known significant interactions.
Adverse reactions reported with 500 mg dose.
Endocrine & metabolic: Hot flushes (7% to 13%)
Hepatic: Alkaline phosphatase increased (>15%; grades 3/4: 1% to 2%), transaminases increased (>15%; grades 3/4: 1% to 2%)
Local: Injection site pain (12% to 14%)
Neuromuscular & skeletal: Joint disorders (14% to 19%)
1% to 10%:
Cardiovascular: Ischemic disorder (1%)
Central nervous system: Fatigue (8%), headache (8%)
Gastrointestinal: Nausea (10%), anorexia (6%), vomiting (6%), constipation (5%), weight gain (≤1%)
Genitourinary: Urinary tract infection (2% to 4%)
Neuromuscular & skeletal: Bone pain (9%), arthralgia (8%), back pain (8%), extremity pain (7%), musculoskeletal pain (6%), weakness (6%)
Respiratory: Cough (5%), dyspnea (4%)
<1% (Limited to important or life-threatening; reported with 250 mg or 500 mg dose): Angioedema, hepatitis, hypersensitivity reactions, leukopenia, liver failure, osteoporosis, thrombosis, vaginal bleeding
Concerns related to adverse effects:
• Hypersensitivity: Hypersensitivity reactions, including urticaria and angioedema, have been reported.
• Bleeding risks: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration.
• Hepatic impairment: Exposure is increased and dosage adjustment is recommended in patients with moderate impairment. Safety and efficacy have not been established in severe impairment.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).
Liver function tests; pregnancy testing is recommended within 7 days prior to fulvestrant initiation (for females of reproductive potential); monitor for signs/symptoms of bleeding
Adverse events were observed in animal reproduction studies. Based on the mechanism of action, fulvestrant may cause fetal harm if administered during pregnancy. For females of reproductive potential, pregnancy testing is recommended within 7 days prior to initiation of fulvestrant and effective contraception should be used during treatment and for 1 year after the last fulvestrant dose. Although not approved for use in men, animal data suggest that fulvestrant may affect male fertility.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience hot flashes, nausea, headache, back pain, constipation, lack of appetite, pharyngitis, or injection site pain or irritation. Have patient report immediately to prescriber paresthesia, depression, severe arthralgia, significant myalgia, considerable osteodynia, angina, dyspnea, intolerable asthenia, dysuria, or difficult urination (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
More about fulvestrant
- Other brands: Faslodex