Fulvestrant

Class: Antineoplastic Agents
VA Class: AN500
Chemical Name: 4′ - [2 - [[(2aE,4E,5′S,6S,6′R,7R,8E,11R,13R,15S,17aR,20R,20aR,20bS) - 6′ - Ethyl - 3′,4′,5′,6,6′,7,10,11,14,15,17a,20,20a,20b - tetradecahydro - 20,20b - dihydroxy - 5′,6,8,19 - furo[4,3,2 - pq][2,6]benzodioxacyclooctadecin - 13,2′[2H]pyran] - 7 - yl]oxy]ethyl] - N - methylmethanesulfonanilide
Molecular Formula: C₃₂H₄₇F₅O₃S
CAS Number: 129453-61-8
Brands: Faslodex

Introduction

Antineoplastic agent; estrogen antagonist.^{1 2}

Uses for Fulvestrant

Breast Cancer

Treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen (e.g., tamoxifen) therapy.^{1 2 4}

Efficacy in premenopausal women (e.g., those with functioning ovaries, as evidenced by menstruation and/or premenopausal LH, FSH, and estradiol concentrations) with advanced breast cancer not established.¹

Fulvestrant Dosage and Administration

General

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  Commercially available as one 5-mL prefilled syringe containing 250 mg (5 mL) of fulvestrant or two 5-mL prefilled syringes, each containing 125 mg (2.5 mL) of fulvestrant (total dose of 250 mg), with safety needles.^{1 4}

  
  


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  Consult manufacturer’s prescribing information for details on assembly and proper use of safety needle.¹

  
  

Administration

IM Administration

Administer IM slowly at the dorsogluteal site or into the upper outer quadrant of the gluteal muscle.^{1 3} Administer as a single 5-mL injection or 2 concurrent 2.5-mL injections, which may be administered bilaterally.¹

Prior to administration, remove injection from refrigeration and keep at room temperature for up to 1 hour or roll gently between the hands.^{3 4}

Dosage

Adults

Breast Cancer

IM

250 mg once monthly.^{1 2 3}

Special Populations

Hepatic Impairment

Dosage adjustments not required in patients with mild hepatic impairment.¹ Safety and efficacy not established in patients with moderate to severe hepatic impairment.¹

Geriatric Patients

Dosage adjustments not required.¹

Cautions for Fulvestrant

Contraindications

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  Known or suspected pregnancy.¹

  
  


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  Known hypersensitivity to fulvestrant, benzyl alcohol, or any ingredient in the formulation.^{1 4}

  
  

Warnings/Precautions

Warnings

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm;¹ teratogenicity and embryolethality demonstrated in animals.¹

Excluded pregnancy prior to administering the first dose of fulvestrant, and avoid pregnancy during therapy.¹ If used during pregnancy or patient becomes pregnant, apprise of potential hazard to the fetus or potential risk for loss of the pregnancy.¹

Hematologic Disorders

Use not recommended in patients with bleeding diatheses or thrombocytopenia or in those receiving anticoagulant therapy because of IM administration.¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Distributed into milk in rats; not known whether fulvestrant is distributed into human milk.¹ Discontinue nursing or the drug.¹

Pediatric Use

Safety and efficacy not established.¹

Geriatric Use

Slightly lower objective response rates in patients ≥65 years of age than in younger adults.¹ No substantial difference in pharmacokinetics relative to younger adults.¹

Hepatic Impairment

No substantial differences in safety or pharmacokinetics in patients with mild hepatic impairment relative to patients with normal hepatic function.¹ Safety and efficacy not established in patients with moderate to severe hepatic impairment.¹

Renal Impairment

Not studied in patients with renal impairment; however plasma fulvestrant concentrations in women with creatinine clearances of ≥30 mL/minute were similar to those in women with normal renal function.¹

Common Adverse Effects

Adverse GI effects^{1 2} (e.g., nausea,^{1 5 6} vomiting,^{1 5 6} constipation,^{1 5 6} diarrhea,^{1 5 6} abdominal pain^{1 5 6} ), headache,^{1 5 6} pain (e.g., back pain),^{1 5} asthenia,¹ vasodilation (hot flushes),^{1 2 5 6} pharyngitis^{1 5 6} .

Interactions for Fulvestrant

Metabolized by CYP3A4 and non-CYP routes.¹

Does not inhibit CYP1A2, 2C9, 2C19, 2D6, or 3A4 in vitro.¹

Drugs Affecting Hepatic Microsomal Enzymes

Inducers of CYP: pharmacokinetic interactions unlikely.¹

Specific Drugs

Drug	Interaction	Comments
Midazolam	Pharmacokinetc interactions unlikely1
Rifampin	Pharmacokinetc interactions unlikely1

Fulvestrant Pharmacokinetics

Absorption

Bioavailability

Following IM administration, peak plasma concentrations are attained at about 7 days and are maintained over a period of at least one month.¹ Following IM injection of 250 mg once every month, steady-state plasma concentrations are attained after 3–6 doses.¹

Distribution

Extent

Extensively and rapidly distributed, principally into the extravascular space.¹

Has been shown to cross the placenta and distribute into milk in rats.¹

Plasma Protein Binding

99% (mainly VLDL, LDL, and HDL lipoprotein fractions).¹

Elimination

Metabolism

Metabolized mainly in the liver.¹ Fulvestrant metabolism appears to involve combinations of a number of possible biotransformation pathways analogous to those of endogenous steroids.¹ Identified metabolites are either less active or exhibit similar activity to fulvestrant in antiestrogen models.¹

In vitro studies indicate that CYP3A4 is the only enzyme involved in fulvestrant oxidation; however, the relative contribution of CYP and non-CYP routes in vivo currently is not known.¹

Elimination Route

Rapidly cleared by the hepatobiliary route with excretion primarily via feces (approximately 90%); renal elimination is negligible (<1%).¹

Half-life

Approximately 40 days.¹

Stability

Storage

Parenteral

Injection

Refrigerate at 2–8°C.¹ Protect from light; store in original carton until time of use.^a

ActionsActions

• 
  

  An estrogen antagonist; a 7α-alkylsulfinyl analog of estradiol.^{1 2}

  
  


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  Does not possess estrogen-agonist activity.¹

  
  


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  Competitively binds to and down-regulates estrogen receptors in human breast cancer cells.^{1 2}

  
  


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  Inhibits the growth of tamoxifen-resistant as well as estrogen-sensitive human breast cancer (MCF-7) cell lines in vitro and in vivo.^{1 2}

  
  


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  May block the uterotropic action of estradiol.^{1 2}

  
  

  Does not exhibit peripheral steroidal effects in postmenopausal women.¹

  
  

Advice to Patients

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  Necessity of advising women to use an effective method of contraception while receiving therapy.⁴ Importance of women informing clinicians immediately if they are or plan to become pregnant or plan to breast-feed.¹ Advise pregnant women of risk to the fetus.¹

  
  


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  Importance of informing clinicians of existing or contemplated therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.¹

  
  


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  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Fulvestrant

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for IM use only	50 mg/mL (125 and 250 mg)	Faslodex (with alcohol, benzyl alcohol, and castor oil; 2.5-mL or 5-mL prefilled disposable syringe)	AstraZeneca

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions May 2004. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. AstraZeneca. Faslodex (fulvestrant) injection prescribing information. Wilmington, DE; 2002 Apr.

2. Curran M, Wiseman L. Fulvestrant. Drugs. 2001; 61:807-13. [PubMed 11398912]

3. Anon. Administration for Faslodex a monthly IM injection. From Faslodex website ()

4. AstraZeneca, Wilmington, DE: personal communication

5. Osborne CK, Pippen J, Jones SE et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol. 2002;20:3386-95

6. Howell A, Robertson JFR, Albano JQ et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J Clin Oncol. 2002;20:3396-403

a. AstraZeneca. Faslodex (fulvestrant) injection prescribing information. Wilmington, DE; 2002 Jul.

More Fulvestrant resources

• Fulvestrant Side Effects (in more detail)
• Fulvestrant Use in Pregnancy & Breastfeeding
• Fulvestrant Support Group
• 3 Reviews for Fulvestrant - Add your own review/rating

• Fulvestrant MedFacts Consumer Leaflet (Wolters Kluwer)


• Fulvestrant Professional Patient Advice (Wolters Kluwer)


• fulvestrant Intramuscular Advanced Consumer (Micromedex) - Includes Dosage Information


• Faslodex Prescribing Information (FDA)


• Faslodex Consumer Overview

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