Fulvestrant 50 mg/mL Injection, Solution
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Estrogen Receptor Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Fulvestrant injection is used alone or in combination with another chemotherapy medication to treat a certain type of hormone receptor positive, advanced breast cancer (breast cancer that depends on hormones such as estrogen to grow) or breast cancer has spread to other parts of the body in women who have experienced menopause (change of life; end of monthly menstrual periods) and have not previously been treated with an anti-estrogen medication such as tamoxifen (Nolvadex). Fulvestrant injection is also used alone or in combination with certain other chemotherapy medications to treat a certai...
Read the full MedlinePlus article ↗- Fulvestrant is a hormonal treatment for a type of breast cancer that is driven by estrogen — specifically, cancer that tests positive for hormone receptors (HR-positive) but negati...
- What exactly is fulvestrant and why did my doctor prescribe it for breast cancer?
- Yes, fulvestrant is given as an injection into the muscle of your buttock — it can't be taken as a pill. A nurse or doctor in your clinic will give it to you. The schedule is: an i...
- How is it given, and do I have to go to the clinic every time?
Patient education
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Some supplements/herbs that may interact with Fulvestrant — tap one for details:
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per mL | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $22.19 | $221.89 / 10 ml |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J9395 | $5.277 / J9395 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Fulvestrant 50 mg/mL 00143-9022-02 | Hikma | 2 syringes | — | AO | FDA listed | — |
| Faslodex 50 mg/mL 00310-0720-10 | AstraZeneca | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 00781-3532-12 | Sandoz | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 00781-9055-12 | Sandoz | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 16714-0070-02 | Northstar | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 250 mg/5mL 16729-0436-30 | Accord | 2 syringes | — | AO | FDA listed | — |
| fulvestrant 50 mg/mL 25021-0471-74 | Sagent | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mLthis 43598-0262-23 | Dr.Reddy's | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 55150-0394-02 | Eugia | 2 syringes | — | — | FDA listed | — |
| Fulvestrant 50 mg/mL 62332-0650-05 | Alembic | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 63323-0715-05 | Fresenius | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 250 mg/5mL 68001-0484-85 | BluePoint | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 250 mg/5mL 68001-0522-85 | BluePoint | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 68001-0626-85 | BluePoint | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 68462-0317-32 | GLENMARK | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 250 mg/5mL 70121-1463-02 | Amneal | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 70700-0284-98 | Xiromed, | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 70710-1688-08 | Zydus | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 70771-1626-08 | Zydus | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 70860-0211-74 | Athenex | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 71288-0555-86 | Meitheal | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 71731-6121-01 | Chia | 2 syringes | — | AO | FDA listed | — |
| Fulvestrant 50 mg/mL 83634-0203-74 | Avenacy, | 2 syringes | — | AO | FDA listed | — |
| Cligavyx 250 mg/5mL 83831-0159-02 | Avyxa | 2 syringes | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 43598-0262-02 | 2 SYRINGE, GLASS in 1 CARTON (43598-262-02) / 5 mL in 1 SYRINGE, GLASS (43598-262-11) | 2020-08-17 | Discontinued by firm |
| 43598-0262-23 You're viewing this | 2 SYRINGE, GLASS in 1 CARTON (43598-262-23) / 5 mL in 1 SYRINGE, GLASS (43598-262-11) | 2024-09-05 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 86% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 43598-0262-23?
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🧭 About this NDC listing & data coverage
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| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available. |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Monotherapy Fulvestrant is indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or Combination Therapy Fulvestrant is indicated for the treatment of: HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy.
HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. Fulvestrant is an estrogen receptor antagonist indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy. ( 1 ) HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy.
( 1) HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy. ( 1) HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. ( 1)
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION •Fulvestrant injection 500 mg should be administered intramuscularly into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as two 5 mL injections, one in each buttock, on Days 1, 15, 29, and once monthly thereafter. ( 2.1 , 14 ) A dose of 250 mg is recommended in patients with moderate hepatic impairment to be administered intramuscularly into the buttock (gluteal area) slowly (1 to 2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter. ( 2.2 , 5.2 , 8.6 )
2.1Recommended Dose Monotherapy The recommended dose of fulvestrant injection is 500 mg to be administered intramuscularly into the buttocks (gluteal area) slowly (1 - 2 minutes per injection) as two 5 mL injections, one in each buttock, on Days 1, 15, 29, and once monthly thereafter [see Clinical Studies ( 14) ] . Combination Therapy When fulvestrant is used in combination with palbociclib, abemaciclib or ribociclib, the recommended dose of fulvestrant is 500 mg to be administered intramuscularly into the buttocks (gluteal area) slowly (1 to 2 minutes per injection) as two 5 mL injections, one in each buttock, on Days 1, 15, 29, and once monthly thereafter.
When fulvestrant is used in combination with palbociclib, the recommended dose of palbociclib is a 125 mg capsule taken orally once daily for 21 consecutive days followed by 7 days off treatment to comprise a complete cycle of 28 days. Palbociclib should be taken with food. Refer to the Full Prescribing Information for palbociclib.
When fulvestrant is used in combination with abemaciclib, the recommended dose of abemaciclib is 150 mg orally, twice daily. Abemaciclib may be taken with or without food. Refer to the Full Prescribing Information for abemaciclib.
When fulvestrant is used in combination with ribociclib, the recommended dose of ribociclib is 600 mg taken orally, once daily for 21 consecutive days followed by 7 days off treatment resulting in a complete cycle of 28 days. Ribociclib can be taken with or without food. Refer to the Full Prescribing Information for ribociclib.
Pre/perimenopausal women treated with the combination of fulvestrant plus palbociclib, abemaciclib, or ribociclib should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards [see Clinical Studies ( 14 )].
2.2Dose Modification Monotherapy Hepatic Impairment : A dose of 250 mg is recommended for patients with moderate hepatic impairment (Child-Pugh class B) to be administered intramuscularly into the buttock (gluteal area) slowly (1 to 2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter. Fulvestrant has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C) [see Warnings and Precautions ( 5.2 ) and Use in Specific Populations ( 8.6 )]. Combination Therapy When fulvestrant is used in combination with palbociclib, abemaciclib or ribociclib refer to monotherapy dose modification instructions for fulvestrant.
Refer to the Full Prescribing Information of co-administered palbociclib, abemaciclib or ribociclib for dose modification guidelines in the event of toxicities, for use with concomitant medications, and other relevant safety information.
2.3Administration Technique Administer the injection according to the local guidelines for performing large volume intramuscular injections. NOTE: Due to the proximity of the underlying sciatic nerve, caution should be taken if administering fulvestrant at the dorsogluteal injection site [see Warnings and Precautions (5.3) and Adverse Reactions (6.1)]. The proper method of administration of fulvestrant injection for intramuscular use is described in the following instructions: For each single-dose prefilled syringe: 1.
Remove glass syringe barrel from tray and check that it is not damaged. 2. Remove perforated patient record label from syringe.
3. Inspect drug product in glass syringe for any visible particulate matter…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Fulvestrant, an injection for intramuscular administration, is supplied as 5-mL single-dose prefilled syringes containing 250 mg/5 mL fulvestrant. Fulvestrant, an injection for intramuscular administration, is supplied as 250 mg/5 mL fulvestrant. (3)
⛔ Contraindications ▾
4 CONTRAINDICATIONS Fulvestrant is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. Hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant [see Adverse Reactions ( 6.2 )]. • Hypersensitivity (4)
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Risk of Bleeding: Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use. ( 5.1 ) Increased Exposure in Patients with Hepatic Impairment: Use a 250 mg dose for patients with moderate hepatic impairment. (2.2 , 5.2 , 8.6 ) Injection Site Reaction: Use caution while administering fulvestrant at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve.
( 5.3 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. (5.4, 8.1 , 8.3 ) Immunoassay Measurement of Serum Estradiol: Fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.
( 5.5 )
5.1Risk of Bleeding Because fulvestrant is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.
5.2Increased Exposure in Patients with Hepatic Impairment The safety and pharmacokinetics of fulvestrant were evaluated in a study in seven subjects with moderate hepatic impairment (Child-Pugh class B) and seven subjects with normal hepatic function. Exposure was increased in patients with moderate hepatic impairment, therefore a dose of 250 mg is recommended [see Dosage and Administration ( 2.2 )]. Fulvestrant has not been studied in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations ( 8.6 )].
5.3Injection Site Reaction Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with fulvestrant injection. Caution should be taken while administering fulvestrant at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve [see Dosage and Administration ( 2.3 ) and Adverse Reactions ( 6.1 )] .
5.4Embryo-Fetal Toxicity 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 with fulvestrant and for one year after the last dose [see Use in Specific Populations ( 8.1 ), ( 8.3 ) and Clinical Pharmacology ( 12.1 )].
5.5Immunoassay Measurement of Serum Estradiol Due to structural similarity of fulvestrant and estradiol, fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels.
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Risk of Bleeding [see Warnings and Precautions ( 5.1 )] Increased Exposure in Patients with Hepatic Impairment [see Warnings and Precautions ( 5.2 )] Injection Site Reaction [see Warnings and Precautions (5.3 )] Embryo-Fetal Toxicity [see Warnings and Precautions ( 5.4 )] • The most common adverse reactions occurring in ≥ 5% of patients receiving fulvestrant 500 mg were: injection site pain, nausea, bone pain, arthralgia, headache, back pain, fatigue, pain in extremity, hot flash, vomiting, anorexia, asthenia, musculoskeletal pain, cough, dyspnea, and constipation.
( 6.1 ) • Increased hepatic enzymes (ALT, AST, ALP) occurred in >15% of fulvestrant patients and were not dose-dependent. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Dr. Reddy’s Laboratories Inc., at 1-888-375-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the adverse reaction rates observed cannot be directly compared to rates in other trials and may not reflect the rates observed in clinical practice. Monotherapy Comparison of Fulvestrant 500 mg and Fulvestrant 250 mg (CONFIRM) The following adverse reactions (ARs) were calculated based on the safety analysis of CONFIRM comparing the administration of fulvestrant 500 mg intramuscularly once a month with fulvestrant 250 mg intramuscularly once a month.
The most frequently reported adverse reactions in the fulvestrant 500 mg group were injection site pain (11.6% of patients), nausea (9.7% of patients) and bone pain (9.4% of patients), the most frequently reported adverse reactions in the fulvestrant 250 mg group were nausea (13.6% of patients), back pain (10.7% of patients) and injection site pain (9.1% of patients). Table 1 lists adverse reactions reported with an incidence of 5% or greater, regardless of assessed causality, from CONFIRM. Table 1: Adverse Reactions in CONFIRM (≥5% in Either Treatment Group) Adverse Reactions Fulvestrant 500 mg N=361 % Fulvestrant 250 mg N=374 % Body as a Whole Injection Site Pain 1 12 9 Headache 8 7 Back Pain 8 11 Fatigue 8 6 Pain in Extremity 7 7 Asthenia 6 6 Vascular System Hot Flash 7 6 Digestive System Nausea 10 14 Vomiting 6 6 Anorexia 6 4 Constipation 5 4 Musculoskeletal System Bone Pain 9 8 Arthralgia 8 8 Musculoskeletal Pain 6 3 Respiratory System Cough 5 5 Dyspnea 4 5 1 Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy.
In the pooled safety population (N=1127) from clinical trials comparing fulvestrant 500 mg to fulvestrant 250 mg, post-baseline increases of ≥1 CTC grade in either AST, ALT, or alkaline phosphatase were observed in > 15% of patients receiving fulvestrant. Grade 3-4 increases were observed in 1-2% of patients. The incidence and severity of increased hepatic enzymes (ALT, AST, ALP) did not differ between the 250 mg and the 500 mg fulvestrant arms.
Comparison of Fulvestrant 500 mg and Anastrozole 1 mg (FALCON) The safety of fulvestrant 500 mg versus anastrozole 1 mg was evaluated in FALCON. The data described below reflect exposure to fulvestrant in 228 out of 460 patients with HR-positive advanced breast cancer in postmenopausal women not previously treated with endocrine therapy who received at least one (1) dose of treatment in FALCON. Permanent discontinuation associated with an adverse reaction occurred in 4 of 228 (1.8%) patients receiving fulvestrant, and in 3 of 232 (1.3%) patients receiving anastrozole.
Adverse reactions leading to discontinuation for those patients receiving fulvestrant included drug hypersensitivity (0.9%), injection site hypersensitivity (0.4%), and elevated liver enzymes (0.4%). The most common adverse reactions (≥10%) of any grade reported in patients in the fulvestrant arm were arthralgia, hot flash, fatigue, and nausea. Adverse reactions r…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS There are no known drug-drug interactions. Although, fulvestrant is metabolized by CYP 3A4 in vitro, drug interactions studies with ketoconazole or rifampin did not alter fulvestrant pharmacokinetics. Dose adjustment is not needed in patients co-prescribed CYP3A4 inhibitors or inducers [see Clinical Pharmacology ( 12.3 )]. • There are no known drug-drug interactions. (7)
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS • Lactation: Advise not to breastfeed. ( 8.2)
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m 2 , respectively [see Data] .
Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m 2 . When fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m 2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. Fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m 2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day.
Fulvestrant administered at 2 mg/kg/day caused fetal loss. When administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m 2 ). Further, at 0.25 mg/kg/day (30% the human dose based on mg/m 2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits.
Fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m 2 ) when administered during the period of organogenesis.
8.2Lactation Risk Summary There is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. Fulvestrant can be detected in rat milk [see Data]. Because of the potential for serious adverse reactions in breastfed infants from fulvestrant, advise a lactating woman not to breastfeed during treatment with fulvestrant and for one year after the final dose.
Data Levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. Drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. In a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m 2 ) during lactation, offspring survival was slightly reduced.
8.3Females and Males of Reproductive Potential Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant. Contraception Females Fulvestrant can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations ( 8.1 ) ] . Advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose.
Infertility Based on animal studies, fulvestrant may impair fertility in females and males of reproductive potential. The effects of fulvestrant on fertility were reversible in female rats [see Nonclinical Toxicology ( 13.1 )]. 8.4…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology ( 12.1 )] . There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m 2 , respectively [see Data] .
Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data Animal Data Administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m 2 . When fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m 2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. Fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m 2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day.
Fulvestrant administered at 2 mg/kg/day caused fetal loss. When administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m 2 ). Further, at 0.25 mg/kg/day (30% the human dose based on mg/m 2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits.
Fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m 2 ) when administered during the period of organogenesis.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established. A multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with McCune-Albright Syndrome (MAS) associated with Progressive Precocious Puberty (PPP). The median age at informed consent was 6 years old (range: 1 to 8).
The first 10 patients initially received fulvestrant 2 mg/kg. Based on PK data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. Baseline measurements for vaginal bleeding days, bone age, growth velocity, and Tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian or local consultant.
All measurements during the study period were collected prospectively. Patients’ baseline characteristics included the following: a mean ± SD chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. Twenty-nine of 30 patients completed the 12-month study period.
The following results were observed: 35% (95% CI: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change = -0.9 [95% CI: -1.4, -0.4]); and a reduction in mean growth velocity Z-score on-treatment compared to baseline (mean change = -1.1 [95% CI: -2.7, 0.4]). There were no clinically meaningful changes in median Tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (PAH) on-treatment compared to baseline.
The effect of fulvestrant on bone mineral density in children has not been studied and is not known. Eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant. These included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting.
Nine (30%) patients reported an SAE, none of which were considered related to fulvestrant. No patients discontinued study treatment due to an AE and no patients died. Pharmacokinetics The pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with PPP associated with MAS.
Pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. In these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (SD) CL/F was 444 (165) mL/min which was 32% lower than adults. The geometric mean (SD) steady state trough concentration (C min,ss ) and AUC ss was 4.19 (0.87) ng/mL and 3680 (1020) ng*hr/mL, respectively.
🧓 Geriatric Use ▾
8.5Geriatric Use For fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant in Study 0021 and Study 0020, respectively.
🆘 Overdosage ▾
10 OVERDOSAGE Human experience of overdose with fulvestrant is limited. There are isolated reports of overdose with fulvestrant in humans. No adverse reactions were seen in healthy male and female volunteers who received intravenous fulvestrant, which resulted in peak plasma concentrations at the end of the infusion, that were approximately 10 to 15 times those seen after intramuscular injection.
The potential toxicity of fulvestrant at these or higher concentrations in cancer patients who may have additional comorbidities is unknown. There is no specific treatment in the event of fulvestrant overdose, and symptoms of overdose are not established. In the event of an overdose, healthcare practitioners should follow general supportive measures and should treat symptomatically.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines.
In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts. Fulvestrant showed no agonist-type effects in in vivo uterotrophic assays in immature or ovariectomized mice and rats.
In in vivo studies in immature rats and ovariectomized monkeys, fulvestrant blocked the uterotrophic action of estradiol. In postmenopausal women, the absence of changes in plasma concentrations of FSH and LH in response to fulvestrant treatment (250 mg monthly) suggests no peripheral steroidal effects.
12.2Pharmacodynamics In a clinical study in postmenopausal women with primary breast cancer treated with single doses of fulvestrant 15-22 days prior to surgery, there was evidence of increasing down- regulation of ER with increasing dose. This was associated with a dose-related decrease in the expression of the progesterone receptor, an estrogen-regulated protein. These effects on the ER pathway were also associated with a decrease in Ki67 labeling index, a marker of cell proliferation.
12.3Pharmacokinetics Absorption: The single dose and multiple dose PK parameters for the 500 mg dosing regimen with an additional dose (AD) at Day 15 are reported in Table 11. The additional dose of fulvestrant given two weeks after the initial dose allows for steady state concentrations to be reached within the first month of dosing. Table 11: Summary of Fulvestrant Pharmacokinetic Parameters [gMean (CV%)] in Postmenopausal Advanced Breast Cancer Patients after Intramuscular Administration 500 mg + AD Dosing Regimen C max (ng/mL) C min (ng/mL) AUC (ng.hr/mL) 500 mg + AD 1 Single dose 25.1 (35.3) 16.3 (25.9) 11400 (33.4) Multiple dose steady state 2 28.0 (27.9) 12.2 (21.7) 13100 (23.4) 1 Additional 500 mg dose given on Day 15 2 Month 3 Distribution: The apparent volume of distribution at steady state is approximately 3 to 5 L/kg.
This suggests that distribution is largely extravascular. Fulvestrant is highly (99%) bound to plasma proteins; VLDL, LDL and HDL lipoprotein fractions appear to be the major binding components. The role of sex hormone-binding globulin, if any, could not be determined.
Metabolism: Biotransformation and disposition of fulvestrant in humans have been determined following intramuscular and intravenous administration of 14 C-labeled fulvestrant. Metabolism of fulvestrant appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids, including oxidation, aromatic hydroxylation, conjugation with glucuronic acid and/or sulphate at the 2, 3, and 17 positions of the steroid nucleus, and oxidation of the side chain sulphoxide. Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models.
Studies using human liver preparations and recombinant human enzymes indicate that cytochrome P-450 3A4 (CYP 3A4) is the only P-450 isoenzyme involved in the oxidation of fulvestrant; however, the relative contribution of P-450 and non-P-450 routes in vivo is unknown. Excretion: Fulvestrant was rapidly cleared by the hepatobiliary route with excretion primarily via the feces (approximately 90%). Renal elimination was negligible (less than 1%).
After an intramuscular injection of 250 mg, the clearance (Mean ± SD) was…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Many breast cancers have estrogen receptors (ER) and the growth of these tumors can be stimulated by estrogen. Fulvestrant is an estrogen receptor antagonist that binds to the estrogen receptor in a competitive manner with affinity comparable to that of estradiol and downregulates the ER protein in human breast cancer cells. In vitro studies demonstrated that fulvestrant is a reversible inhibitor of the growth of tamoxifen-resistant, as well as estrogen-sensitive human breast cancer (MCF-7) cell lines.
In in vivo tumor studies, fulvestrant delayed the establishment of tumors from xenografts of human breast cancer MCF-7 cells in nude mice. Fulvestrant inhibited the growth of established MCF-7 xenografts and of tamoxifen-resistant breast tumor xenografts. Fulvestrant showed no agonist-type effects in in vivo uterotrophic assays in immature or ovariectomized mice and rats.
In in vivo studies in immature rats and ovariectomized monkeys, fulvestrant blocked the uterotrophic action of estradiol. In postmenopausal women, the absence of changes in plasma concentrations of FSH and LH in response to fulvestrant treatment (250 mg monthly) suggests no peripheral steroidal effects.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Fulvestrant injection is supplied as two 5-mL clear neutral glass (Type 1) barrels, each containing 250 mg/5 mL of fulvestrant solution for intramuscular injection and fitted with a tamper evident closure.The solution for injection is a clear, colorless to yellow, viscous liquid. NDC 43598-262-23 The carton containing 2 single-dose pre-filled syringes in a thermoformed blister and safety needles (SurGuard ® 3 Safety Hypodermic Needle) Discard each syringe after use. If a patient dose requires only one syringe, unused syringe should be stored as directed below.
Storage: Store at 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Fulvestrant Injection can also be stored at refrigerated conditions: 2°C to 8°C (36°F to 46°F). TO PROTECT FROM LIGHT, STORE IN THE ORIGINAL CARTON UNTIL TIME OF USE.
📋 Description ▾
1 1 DESCRIPTION Fulvestrant injection for intramuscular administration is an estrogen receptor antagonist. The chemical name is 7-α-[9-(4,4,5,5,5-penta fluoropentylsulphinyl) nonyl]estra-1,3,5-(10)- triene-3,17β-diol. The molecular formula is C 32 H 47 F 5 O 3 S and its structural formula is: Fulvestrant is a white powder with a molecular weight of 606.77.
The solution for injection is a clear, colorless to yellow, viscous liquid. Each injection contains as inactive ingredients:12% v/v of absolute alcohol at 60°F (15.56°C); 10% w/v Benzyl Alcohol, NF, and 15% w/v Benzyl Benzoate, USP as co-solvents, and made up to 100% w/v with Castor Oil, USP as a co-solvent and release rate modifier.
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information) Monotherapy Risk of Bleeding: • Because fulvestrant is administered intramuscularly, it should be used with caution in patients with bleeding disorders, decreased platelet count, or in patients receiving anticoagulants (for example, warfarin) [see Warnings and Precautions ( 5.1 )]. Embryo-Fetal Toxicity: • Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment with fulvestrant and for one year after the last dose.
Advise females to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.4 ) and Use in Specific Populations ( 8.1 ), ( 8.3 )]. Lactation: • Advise women not to breastfeed during treatment with fulvestrant and for one year after the last dose [see Use in Specific Populations ( 8.2 )]. Combination Therapy When fulvestrant is used in combination with palbociclib, abemaciclib, or ribociclib, refer to the respective Full Prescribing Information for Patient Counseling Information.