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, monotherapy (postmenopausal women; HR positive): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly
Breast cancer, advanced, monotherapy (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, combination therapy (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, combination therapy (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.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, renal elimination of fulvestrant is negligible.
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Pugh class B): Reduce initial and maintenance doses: Initial: 250 mg on days 1, 15, and 29; Maintenance: 250 mg once monthly.
Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (use has not been evaluated).
(For additional information see "Fulvestrant: Pediatric drug information")
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).
There are no pediatric-specific recommendations available; based on experience in adult patients, renal elimination of fulvestrant is negligible.
There are no pediatric-specific recommendations available; based on experience in adult patients, dosing adjustment is suggested.
Refer to adult dosing.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, 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)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, 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)
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.
For IM administration only; inject slowly over 1 to 2 minutes per injection; do not administer IV, SubQ, or intra-arterially. Pediatric patients may be able to receive entire dose as one injection; maximum dose volume in adults: 5 mL per injection per buttock.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, administration, and disposal. Gloves (single) should be worn during receiving, unpacking, and placing in storage.
NIOSH recommends double gloving, a protective gown, ventilated engineering controls (a class II biological safety cabinet or a compounding aseptic containment isolator), and closed system transfer devices (CSTDs) for preparation. Double gloving and a protective gown are recommended during administration (NIOSH 2016).
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
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Endocrine & metabolic: Decreased serum glucose (18%), hot flash (7% to 11%), increased gamma-glutamyl transferase (49%)
Gastrointestinal: Abdominal pain (13% to 16%), constipation (5% to 12%), decreased appetite (8% to 13%), diarrhea (6% to 25%), nausea (10% to 28%), stomatitis (10% to 13%), vomiting (6% to 15%)
Hematologic & oncologic: Anemia (4% to 40%; grade 3: ≤2%), lymphocytopenia (35%; grade 3: 2%)
Hepatic: Increased liver enzymes (>15%), increased serum alanine aminotransferase (5% to 37%), increased serum aspartate aminotransferase (5% to 48%)
Infection: Infection (25% to 31%)
Local: Pain at injection site (12%)
Nervous system: Fatigue (8% to 32%), headache (8% to 15%)
Neuromuscular & skeletal: Arthralgia (8% to 17%)
Respiratory: Cough (5% to 15%), dyspnea (4% to 12%)
1% to 10%:
Cardiovascular: Peripheral edema (7%)
Dermatologic: Alopecia (2% to 6%), pruritus (6% to 7%), skin rash (4% to 7%)
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%), neutropenia (2%; grade 3: 1%; grade 4: <1%), thrombocytopenia (3%; grade 4: <1%)
Nervous system: Dizziness (6% to 8%)
Neuromuscular & skeletal: Asthenia (5% to 6%), back pain (8% to 9%), limb pain (6% to 7%), musculoskeletal pain (6%), myalgia (7%), ostealgia (9%)
Miscellaneous: Fever (5% to 7%)
Frequency not defined:
Nervous system: Neuralgia, peripheral neuropathy, sciatica
Renal: Increased serum creatinine
Postmarketing:
Cardiovascular: Venous thromboembolism
Genitourinary: Vaginal hemorrhage
Hepatic: Hepatic failure, hepatitis, increased serum bilirubin
Known hypersensitivity to fulvestrant or any component of the formulation
Canadian labeling: Additional contraindications (not in the US labeling): Pregnant or lactating women
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.
Substrate of CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Fluoroestradiol F18: Estrogen Receptor Antagonists may diminish the diagnostic effect of Fluoroestradiol F18. Management: Image patients with fluoroestradiol F-18 prior to starting systemic endocrine therapies that block the estrogen receptor. Use of fluoroestradiol F-18 should not delay indicated treatment. Risk D: Consider therapy modification
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.
Based on findings from animal reproduction studies and the mechanism of action, fulvestrant may cause fetal harm if administered during pregnancy.
It is not known if fulvestrant is present in breast milk. Because of the potential for serious adverse reactions in the breastfed infant, lactating women should not breastfeed during treatment and for 1 year after the final fulvestrant dose.
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
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.
Duration: 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
Distribution: Vd: ~3 to 5 L/kg
Protein binding: 99%; to plasma proteins (VLDL, LDL and HDL lipoprotein fractions)
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
Half-life elimination:
Children 1.7 to 8.5 years: 70.4 ± 8.1 days (Sims 2012)
Adults: 250 mg: ~40 days
Excretion: Feces (~90%); urine (<1%)
Clearance: Children 1 to 8 years (based on a 4 mg/kg dose): Decreased by 32% compared to adults
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.
Solution Prefilled Syringe (Faslodex Intramuscular)
250 mg/5 mL (per mL): $232.69
Solution Prefilled Syringe (Fulvestrant Intramuscular)
250 mg/5 mL (per mL): $36.00 - $218.15
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
