CLIGAVYX fulvestrant 250 mg/5mL Injection
🆔 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...
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Patient education
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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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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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/mL 43598-0262-02 | Dr.Reddy's | 2 syringes | — | AO | Discontinued | — |
| 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/5mLthis 83831-0159-02 | Avyxa | 2 syringes | — | — | FDA listed | — |
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⏳ Availability & generic status
The FDA lists approved generic versions of this medicine, but that does not always mean a pharmacy can get one today. Patent rules, launch agreements, supply and pricing can affect when generics actually arrive.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 83831-0159-02 You're viewing this | 2 SYRINGE, GLASS in 1 CARTON (83831-159-02) / 5 mL in 1 SYRINGE, GLASS | 2026-07-01 | Active |
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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) | ✓ 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 | — Not published for this NDC Applies only to products approved under an NDA/ANDA; many listings are out of scope. |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Monotherapy CLIGAVYX 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 HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy CLIGAVYX 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. CLIGAVYX 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 The recommended dosage of CLIGAVYX is 500 mg 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 ) The dosage of CLIGAVYX for patients with moderate hepatic impairment is 250 mg 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 , 8.6 )
2.1Recommended Dose The recommended dose of CLIGAVYX 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 [see Clinical Studies (14) ] . Pre/perimenopausal women who will receive CLIGAVYX 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) ] .
Refer to the respective Full Prescribing Information for each therapeutic agent administered in combination with CLIGAVYX for the recommended dosage information, as appropriate.
2.2Dosage in Patients with Hepatic Impairment In patients with moderate hepatic impairment (Child-Pugh Class B), the recommended dosage is 250 mg 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. CLIGAVYX has not been evaluated in patients with severe hepatic impairment (Child-Pugh class C) [see Use in Specific Populations (8.6) ] . When CLIGAVYX is used in combination with palbociclib, abemaciclib, or ribociclib, refer to monotherapy dose modification instructions for CLIGAVYX.
Refer to the respective Full Prescribing Information for each therapeutic agent administered in combination with CLIGAVYX for dosage modifications in patients with hepatic impairment.
2.3Preparation and Administration 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 CLIGAVYX at the dorsogluteal injection site [see Warnings and Precautions (5.2) and Adverse Reactions (6.1) ] . The proper method of administration of CLIGAVYX for intramuscular use is described in the following instructions.
For each single-dose prefilled syringe: Remove glass syringe barrel from tray and check that it is not damaged. Remove perforated patient record label from syringe. Inspect drug product in glass syringe for any visible particulate matter or discoloration prior to use.
Discard if particulate matter or discoloration is present. Peel open the safety needle (SafetyGlide ™ ) outer packaging. Hold the syringe upright on the ribbed part (C).
With the other hand, take hold of the cap (A) and carefully TWIST THE CAP COUNTER-CLOCKWISE until the cap disconnects for removal (see Figure 1). 6. Pull the cap (A) off in a straight upward direction.
DO NOT TOUCH THE STERILE SYRINGE TIP (Luer-Lok) (B) (see Figure 2). 7. Attach the safety needle to the syringe tip (Luer-Lok).
Twist needle until firmly seated (see Figure 3). Confirm that the needle is locked to the Luer connector before moving or tilting the syringe out of the vertical plane to avoid spillage of syringe contents. For Administration: 8.
Pull shield straight off needle to avoid damaging needle point. 9. Remove needle sheath.
10. Expel excess gas from the syringe (a small gas bubble may remain). 11.
Administer intramuscularly slowly (1 to 2 minutes/injection) into the buttock (gluteal area). For user convenience, the needle 'bevel up' position is orientated to the lever arm, as shown in Figure 4. 12.
After injection, immediately activate the lever arm to deploy the needle shielding by applying a single-finger stroke to the activation assisted lever a…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS CLIGAVYX, an injection for intramuscular administration, is supplied as two 5-mL single-dose prefilled syringes. Each syringe contains 250 mg/5 mL of fulvestrant, USP as a sterile, clear, colorless to yellow solution. CLIGAVYX, an injection for intramuscular administration, is supplied as 250 mg/5 mL of fulvestrant in a single-dose prefilled syringe ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS CLIGAVYX 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 CLIGAVYX [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 ) Injection Site Reaction: Use caution while administering CLIGAVYX at the dorsogluteal injection site due to the proximity of the underlying sciatic nerve. ( 5.2 ) Embryo-Fetal Toxicity: Can cause fetal harm.
Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.3 , 8.1 , 8.3 ) Immunoassay Measurement of Serum Estradiol: CLIGAVYX can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels. ( 5.4 )
5.1Risk of Bleeding Because CLIGAVYX is administered intramuscularly, it should be used with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.
5.2Injection Site Reaction Injection site related events including sciatica, neuralgia, neuropathic pain, and peripheral neuropathy have been reported with fulvestrant. Caution should be taken while administering CLIGAVYX 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) ] .
5.3Embryo-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 CLIGAVYX and for one year after the last dose [see Use in Specific Populations (8.1) , (8.3) and Clinical Pharmacology (12.1) ] .
5.4Immunoassay 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) ] Injection Site Reaction [see Warnings and Precautions (5.2) ] Embryo-Fetal Toxicity [see Warnings and Precautions (5.3) ] 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-treated patients and were not dose-dependent. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma, LLC at 1-888-520-0954 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) 1.
Including more severe injection site related sciatica, neuralgia, neuropathic pain, and peripheral neuropathy. 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 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% to 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 reported in patients who received fulvestrant in FALCON at an incidence of ≥5% in either treatment…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS
7.1Interference of Fulvestrant with Serum Estradiol Immunoassays Due to structural similarity of fulvestrant and estradiol, fulvestrant can interfere with estradiol measurement by immunoassay, resulting in falsely elevated estradiol levels [see Warnings and Precautions (5.4) ] .
👥 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, CLIGAVYX 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 CLIGAVYX, advise a lactating woman not to breastfeed during treatment with CLIGAVYX 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 CLIGAVYX. Contraception Females CLIGAVYX 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, CLIGAVYX 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 Pediatric Use Saf…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, CLIGAVYX 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 2.0 ± 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 CLIGAVYX 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 No overall differences in safety and effectiveness of fulvestrant were observed between older and younger patients.
🧬 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 to 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 CLIGAVYX 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 C min AUC (ng/mL) (ng/mL) (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) wa…
🧬 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 CLIGAVYX TM (fulvestrant) injection is supplied as two 5 mL clear neutral glass (Type 1) barrels, each containing 250 mg/5 mL of sterile, nonpyrogenic, clear, colorless to yellow CLIGAVYX solution for intramuscular injection and fitted with a luer lock connector. The rubber plunger is not made with natural rubber latex. NDC 83831-159-02 The single-dose prefilled syringes are presented in a tray with polystyrene plunger rod and safety needles (SafetyGlide ™ ) for connection to the barrel.
If a patient dose requires only one syringe, unused syringe should be stored as directed below. Storage: REFRIGERATE, 2°-8°C (36°-46°F). TO PROTECT FROM LIGHT, STORE IN THE ORIGINAL CARTON UNTIL TIME OF USE .
📋 Description ▾
11 DESCRIPTION CLIGAVYX injection for intramuscular administration is an estrogen receptor antagonist. The chemical name is 7-alpha-[9-(4,4,5,5,5-penta fluoropentylsulphinyl) nonyl]estra-1,3,5-(10)-triene-3,17-beta-diol. The molecular formula is C 32 H 47 F 5 O 3 S and its structural formula is: Fulvestrant, USP is a white powder with a molecular weight of 606.77.
The sterile injection solution is a clear, colorless to yellow viscous liquid supplied in two 5 mL single-dose prefilled syringes each containing 250 mg/5 mL of fulvestrant, USP for intramuscular administration. CLIGAVYX contains the following inactive ingredients in each 5 mL syringe: benzyl alcohol 500 mg (10% w/v) and dehydrated alcohol 500 mg (10% w/v); castor oil 3000 mg (60% w/v), medium chain triglycerides q.s. to 5 mL (10.8% w/v), and nitrogen q.s. Image
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Risk of Bleeding: Because CLIGAVYX 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 CLIGAVYX 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 (5.3) and Use in Specific Populations (8.1) , (8.3) ] . Lactation: Advise women not to breastfeed during treatment with CLIGAVYX and for one year after the last dose [see Use in Specific Populations (8.2) ] . Combination Therapy When CLIGAVYX is used in combination with palbociclib, abemaciclib, or ribociclib, refer to the respective Full Prescribing Information for Patient Counseling Information.
Manufactured for: Avyxa Pharma, LLC New Jersey 07054, USA Made in China Image