Version July 2025
McCune-Albright syndrome (MAS); progressive precocious puberty: Limited data available (Ref): 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 (Ref).
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.
(For additional information see "Fulvestrant: Drug information")
Dosage guidance:
Dosing: In a dose comparison study, the once monthly fulvestrant maintenance dose was administered at 28 days ± 3 days (Ref). Refer to the protocol or institutional guidance for additional details on off-label dosing.
Breast cancer, advanced, hormone receptor positive (as a single agent; postmenopausal patients; with disease progression following endocrine therapy): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly (Ref).
Breast cancer, advanced, hormone receptor positive (as a single agent; HER2-negative postmenopausal patients; not previously treated with endocrine therapy): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly (Ref).
Breast cancer, advanced or metastatic, hormone receptor positive, HER2-negative (combination therapy; postmenopausal patients; initial endocrine-based therapy or following disease progression on endocrine therapy): Note: A luteinizing hormone-releasing hormone (LHRH) agonist should be administered to pre-/perimenopausal patients receiving fulvestrant in combination with ribociclib (Ref).
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 (Ref).
Breast cancer, advanced or metastatic, hormone receptor positive, HER2-negative (combination therapy; pre- or postmenopausal patients; with disease progression on endocrine therapy): Note: An LHRH agonist should be administered to pre- or perimenopausal patients receiving fulvestrant in combination with abemaciclib or palbociclib (Ref).
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 (Ref).
Breast cancer, advanced or metastatic, hormone receptor positive, HER2-negative (off-label combinations):
PIK3CA-mutated: Males and postmenopausal patients: IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days (in combination with alpelisib); continue until disease progression or unacceptable toxicity (Ref).
PIK3CA-mutated: Males, pre- or peri-menopausal patients, and postmenopausal patients: Note: For pre- and peri-menopausal patients and males, also administer an LHRH agonist (according to current clinical practice standards) for the duration of treatment (Ref).
IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days (in combination with inavolisib and palbociclib); continue until disease progression or unacceptable toxicity (Ref).
PIK3CA, AKT1, and/or PTEN-altered: Note: For pre- and perimenopausal patients, also administer an LHRH agonist (according to current clinical practice standards) (Ref). For male patients, consider administering an LHRH agonist (according to current clinical practice standards) (Ref).
IM: Initial: 500 mg on days 1, 15, and 29; maintenance: 500 mg once every 28 days (in combination with capivasertib); continue until disease progression or unacceptable toxicity (Ref).
Aromatase-inhibitor resistant disease: Postmenopausal patients: IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once every 28 days (in combination with everolimus); continue until disease progression or unacceptable toxicity (Ref).
Breast cancer , metastatic, hormone receptor positive (off-label combination):
Postmenopausal patients: IM: Initial: 500 mg on day 1, 15, and 29; Maintenance: 500 mg once every 28 days (in combination with anastrozole); continue until disease progression or unacceptable toxicity (Ref).
Breast cancer, unresectable locally advanced, recurrent, or metastatic, hormone receptor positive, HER2 positive (off-label combination): Pre- or perimenopausal and postmenopausal patients: Note: For pre- and perimenopausal patients, also administer a gonadotropin-releasing hormone agonist beginning at least 28 days prior to day 1 of cycle 1 (Ref).
IM: Initial: 500 mg on days 1 and 15 of cycle 1 (cycle is 21 days), then 500 mg on day 8 of cycle 2, followed by maintenance dosing of 500 mg once every 28 days; in combination with trastuzumab and abemaciclib; continue until disease progression or unacceptable toxicity (Ref).
Breast cancer in male patients, advanced or metastatic, hormone receptor positive, HER2 negative (off-label use): According to ASCO guidelines for management of male breast cancer, fulvestrant may be used in males with advanced or metastatic HR-positive, HER2-negative breast cancer; males who develop recurrent metastatic, HR-positive, HER2-negative breast cancer while receiving adjuvant endocrine therapy should be offered an alternative endocrine therapy; fulvestrant should not be used in visceral crisis or rapidly progressing disease. Endocrine therapy for males with advanced or metastatic, HR-positive, HER2-negative breast cancer may be sequenced as in females. Metastatic breast cancer in males is treated with the same endocrine therapy as in females (Ref). Note: Other medications (abemaciclib, palbociclib, and ribociclib) have approval for use in combination with fulvestrant in male patients with advanced or metastatic breast cancer with disease progression.
Endometrial cancer, recurrent or metastatic (off-label use): IM: 500 mg once every 28 days for at least 12 weeks or until disease progression or unacceptable toxicity or consider an initial dose of 500 mg on day 1, 15, and 29; followed by 500 mg once every 28 days until disease progression or unacceptable toxicity may be considered (Ref).
There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); however, kidney elimination of fulvestrant is negligible.
Mild impairment (Child-Turcotte-Pugh class A): No dosage adjustment necessary.
Moderate impairment (Child-Turcotte-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-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).
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 patients.
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.
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.
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
Solution Prefilled Syringe (Faslodex Intramuscular)
250 mg/5 mL (per mL): $232.69
Solution Prefilled Syringe (Fulvestrant Intramuscular)
250 mg/5 mL (per mL): $18.00 - $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.
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)
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.
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.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
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.
Treatment of hormone-receptor (HR)-positive advanced breast cancer (as monotherapy) in postmenopausal women with disease progression following endocrine therapy; treatment of HR-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (as monotherapy) in postmenopausal women not previously treated with 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 (All indications: FDA approved in adults); has also been used in treatment of McCune-Albright Syndrome (MAS) in girls associated with progressive precocious puberty
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 drug interactions program by clicking on the “Launch drug interactions program” link above.
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 drug interactions program
Fluoroestradiol F18: Coadministration of Estrogen Receptor Antagonists and Fluoroestradiol F18 may alter diagnostic results. Risk X: Avoid
For patients who could become pregnant, 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, in utero exposure to fulvestrant may cause fetal harm.
McCune-Albright syndrome: In the pediatric clinical trial (study duration: 12 months), the following were monitored: Serum estradiol, testosterone, LH, and FSH (baseline, and at 3, 6, 12 months of therapy); liver function test (baseline and at 12 months of therapy); CBC and INR at baseline; assessments of puberty status and growth at baseline and periodically during therapy (6 and 12 months: height, weight, Tanner stage, bone age [radiographs], vaginal bleeding data, and pelvic ultrasounds) (Sims 2012)
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.
