Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intramuscular:
Faslodex: 250 mg/5 mL (5 mL) [contains alcohol, usp, benzyl alcohol, benzyl benzoate, castor oil (ricine oil)]
Generic: 250 mg/5 mL (5 mL)
Pharmacology
Mechanism of Action
Fulvestrant is an 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.
Pharmacokinetics/Pharmacodynamics
Distribution
Vd: ~3 to 5 L/kg
Metabolism
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
Excretion
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
Half-Life Elimination
Children 1.7 to 8.5 years: 70.4 ± 8.1 days (Sims 2012)
Adults: 250 mg: ~40 days
Protein Binding
99%; to plasma proteins (VLDL, LDL and HDL lipoprotein fractions)
Use in Specific Populations
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 (monotherapy):
Treatment of hormone-receptor (HR)-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy
Treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy
Breast cancer (combination therapy):
Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer (in combination with ribociclib) in postmenopausal women as initial endocrine-based therapy or following disease progression on endocrine therapy
Treatment of HR-positive, HER2-negative advanced or metastatic breast cancer (in combination with palbociclib or abemaciclib) in women with disease progression following endocrine therapy
Contraindications
Known hypersensitivity to fulvestrant or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Pregnant or lactating women
Dosage and Administration
Dosing: Adult
Note: A luteinizing hormone-releasing hormone (LHRH) agonist should be administered to pre-/perimenopausal women receiving fulvestrant in combination with abemaciclib, palbociclib, or ribociclib. In a dose comparison study, the once monthly fulvestrant maintenance dose was administered at 28 days ± 3 days (Di Leo 2014).
Breast cancer, advanced (postmenopausal women; HR positive): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly
Breast cancer, advanced (postmenopausal women; HR positive, HER2 negative): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly (Robertson 2016)
Breast cancer, advanced or metastatic (postmenopausal women; HR positive, HER2 negative): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days. Administer in combination with ribociclib; continue until disease progression or unacceptable toxicity (Slamon 2018). Note: Refer to Ribociclib monograph for ribociclib dosing in combination with fulvestrant.
Breast cancer, advanced or metastatic (second-line endocrine-based combination therapy): Adult females (HR positive, HER2-negative): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days. Administer in combination with palbociclib or abemaciclib; continue until disease progression or unacceptable toxicity (Sledge 2017; Turner 2018). Note: Refer to Palbociclib or Abemaciclib monograph for palbociclib or abemaciclib dosing in combination with fulvestrant.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
McCune-Albright Syndrome (MAS); progressive precocious puberty: Limited data available (Neyman 2017): Female children 1 to 10 years: IM: 4 mg/kg once monthly; dosing based on a trial in 30 girls ≤10 years of age (range: 1 to 8.5 years) who received monthly injections for 1 year; significant decrease in vaginal bleeding and reduction in rates of skeletal maturation were reported (Sims 2012)
Administration
IM: For IM administration only. Administer 500 mg dose as two 5 mL IM injections (one in each buttocks [gluteal area]) slowly over 1 to 2 minutes per injection. If administering at the dorsogluteal site, use caution during injection due to the proximity of underlying sciatic nerve. Refer to facility policy for IM administration of large volumes.
To prepare each syringe for administration, hold syringe upright; carefully tilt syringe cap back and forth (without twisting) until the cap disconnects for removal; pull cap off by pulling up without touching the syringe tip (to maintain sterility); attach safety needle to syringe tip and twist firmly to lock. Remove needle cap by pulling straight off to avoid damaging needle point, remove needle sheath and expel excess air from syringe prior to administration. Refer to product labeling for detailed instructions.
Storage
Storage requirements may vary by product; also refer to manufacturer's labeling.
Refrigerated storage only formulations: Store in original carton at 2°C to 8°C (36°F to 46°F). Protect from light.
Variable temperature storage formulations: May store refrigerated between 2°C to 8°C (36°F to 46°F) or at room temperature between 20°C to 25°C (68°C to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Do not freeze; store in original carton to protect from light.
Drug Interactions
There are no known significant interactions.
Test Interactions
Due to a similarity in structures, fulvestrant may interfere with estradiol immunoassay, resulting in falsely elevated estradiol levels.
Adverse Reactions
>10%:
Central nervous system: Fatigue (8% to 32%), headache (8% to 15%)
Endocrine & metabolic: Increased gamma-glutamyl transferase (49%), decreased serum glucose (18%), hot flash (7% to 11%)
Gastrointestinal: Nausea (10% to 28%), diarrhea (6% to 25%), abdominal pain (13% to 16%), vomiting (6% to 15%), stomatitis (10% to 13%), decreased appetite (8% to 13%), constipation (5% to 12%)
Hematologic & oncologic: Anemia (4% to 40%; grade 3: ≤2%), lymphocytopenia (35%; grade 3: 2%)
Hepatic: Increased serum aspartate aminotransferase (5% to 48%), increased serum alanine aminotransferase (5% to 37%), increased liver enzymes (>15%)
Infection: Infection (25% to 31%)
Local: Pain at injection site (12%)
Neuromuscular & skeletal: Arthralgia (8% to 17%)
Renal: Increased serum creatinine (≤74%)
Respiratory: Cough (5% to 15%), dyspnea (4% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (7%)
Central nervous system: Dizziness (6% to 8%)
Dermatologic: Pruritus (6% to 7%), skin rash (4% to 7%), alopecia (2% to 6%)
Endocrine & metabolic: Decreased serum albumin (8%), decreased serum phosphate (8%), weight loss (2%)
Gastrointestinal: Anorexia (6%), dysgeusia (3%)
Hematologic & oncologic: Leukopenia (≤5%; grade 3: 1%; grade 4: 1%), thrombocytopenia (3%; grade 4: <1%), neutropenia (2%; grade 3: 1%; grade 4: <1%)
Neuromuscular & skeletal: Ostealgia (9%), back pain (8% to 9%), myalgia (7%), limb pain (6% to 7%), musculoskeletal pain (6%), asthenia (5% to 6%)
Miscellaneous: Fever (5% to 7%)
Frequency not defined: Central nervous system: Neuralgia, peripheral neuropathy, sciatica
<1%, postmarketing, and/or case reports: Hepatic failure, hepatitis, increased serum bilirubin, vaginal hemorrhage, venous thromboembolism
Warnings/Precautions
Concerns related to adverse effects:
- Hypersensitivity: Hypersensitivity reactions, including urticaria and angioedema, have been reported.
- Injection-site reactions: Events related to injection site, including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy, have been reported with fulvestrant administration. Due to the proximity of underlying sciatic nerve, use caution if administering at the dorsogluteal site.
Disease-related concerns:
- Bleeding disorders: 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 suggest 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.
Monitoring Parameters
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
Pregnancy
Pregnancy Considerations
Based on findings from animal reproduction studies and 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.
Patient Education
What is this drug used for?
- It is used to treat breast cancer.
- This drug may be used with other drugs to treat your health condition. If you are also taking other drugs, talk with your doctor about the risks and side effects that may happen.
Frequently reported side effects of this drug
- Hot flashes
- Nausea
- Loss of strength and energy
- Vomiting
- Headache
- Back pain
- Bone pain
- Muscle pain
- Joint pain
- Constipation
- Painful extremities
- Lack of appetite
- Cough
- Throat irritation
- Abdominal pain
- Pelvic pain
- Diarrhea
- Dizziness
- Fatigue
- Trouble sleeping
- Sweating a lot
- Flu-like symptoms
- Injection site pain
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Infection
- Urinary tract infection like blood in the urine, burning or painful urination, passing a lot of urine, fever, lower abdominal pain, or pelvic pain.
- Leg numbness or tingling
- Leg weakness
- Anxiety
- Bruising
- Bleeding
- Depression
- Chest pain
- Shortness of breath
- Swelling of arms or legs
- Signs of a significant reaction like 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. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
