Fulvestrant

FDA Drug Information • Also known as: Faslodex, Fulvestrant

Brand Names: Faslodex, Fulvestrant
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Fulvestrant 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 C32H47F5O3S 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: 10% w/v Alcohol, USNF (equivalent to 12.2549% v/v Alcohol, USNF), 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. chemical structure Fulvestrant

What Is Fulvestrant Used For?

1 INDICATIONS AND USAGE Monotherapy Fulvestrant injection 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 Fulvestrant injection 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 injection 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 - 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 - 2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter. ( 2.2 , 5.2 , 8.6 ) 2.1 Recommended 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 injection is used in combination with palbociclib, abemaciclib, or ribociclib, 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. When Fulvestrant injection 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 injection 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 injection 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 injection 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) ] . 2.2 Dose 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 - 2 minutes) as one 5 mL injection on Days 1, 15, 29, and once monthly thereafter. Fulvestrant injection 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 injection is used in combination with...

Side Effects (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 injection 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 injection patients and were not dose-dependent. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Accord Healthcare Inc. at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical 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 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 reported in patients who received Fulvestrant in FALCON at an incidence of ≥5% in either treatment arm are...

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 CYP 3A4 inhibitors or inducers [see Clinical Pharmacology (12.3) ] . There are no known drug-drug interactions. (7)

Contraindications

4 CONTRAINDICATIONS Fulvestrant injection 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 injection [see Adverse Reactions (6.2) ]. Hypersensitivity. (4)

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, Fulvestrant injection 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 2-4% and 15-20%, 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...

Overdosage

10 OVERDOSAGE Human experience of overdose with Fulvestrant injection is limited. There are isolated reports of overdose with Fulvestrant injection 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Fulvestrant injection is supplied as two 5 mL clear glass (Type 1) barrels, each containing 250 mg/5 mL of Fulvestrant solution for intramuscular injection and fitted with a tamper evident closure. Fulvestrant Injection is a clear, colorless to yellow, viscous solution. 5 mL single-dose pre-filled syringe: NDC 68001-522-86 Two pre-filled syringes each containing 250 mg/5 mL of Fulvestrant solution for intramuscular injection and two safety needles (SafetyGlide™) are packaged per carton with NDC 68001-522-85 The single-dose prefilled syringes are presented in a tray with polypropylene plunger rod and safety needles (SafetyGlide™) for connection to the barrel. Discard each syringe after use. If a patient dose requires only one syringe, unused syringe should be stored as directed below. Storage: REFRIGERATE, 2°C TO 8°C (36°F TO 46°F). TO PROTECT FROM LIGHT, STORE IN THE ORIGINAL CARTON UNTIL TIME OF USE .

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.