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Fulvestrant

Pronunciation

(fool VES trant)

Index Terms

  • ICI-182,780
  • ZD9238

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intramuscular:

Faslodex: 250 mg/5 mL (5 mL) [contains alcohol, usp, benzyl alcohol, benzyl benzoate]

Brand Names: U.S.

  • Faslodex

Pharmacologic Category

  • Antineoplastic Agent, Estrogen Receptor Antagonist

Pharmacology

Estrogen receptor antagonist; competitively binds to estrogen receptors on tumors and other tissue targets, producing a nuclear complex that causes a dose-related down-regulation of estrogen receptors and inhibits tumor growth.

Distribution

Vd: ~3 to 5 L/kg

Metabolism

Hepatic via multiple biotransformation pathways (CYP3A4 substrate involved in oxidation pathway, although relative contribution to metabolism unknown); metabolites formed are either less active or have similar activity to parent compound

Excretion

Feces (~90%); urine (<1%)

Clearance: Children 1-8 years: Decreased by 32% compared to adults

Duration of Action

IM: Steady state concentrations reached within first month, when administered with additional dose given 2 weeks following the initial dose; plasma levels maintained for at least 1 month

Half-Life Elimination

Children 1-10 years: 70.4 days (Sims 2012)

Adults 250 mg: ~40 days

Protein Binding

99%; to plasma proteins (VLDL, LDL and HDL lipoprotein fractions)

Special Populations: Hepatic Function Impairment

In moderate hepatic impairment (Child-Pugh class B), the average AUC of fulvestrant increased by 70% compared with patients with normal hepatic function.

Use: Labeled Indications

Breast cancer, metastatic: Treatment of hormone-receptor–positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy

Contraindications

Known hypersensitivity to fulvestrant or any component of the formulation

Dosage

Breast cancer, metastatic: Adults (postmenopausal women): IM: Initial: 500 mg on days 1, 15, and 29; Maintenance: 500 mg once monthly. In studies, the 500 mg once monthly dose was administered at 28 days ± 3 days (Di Leo, 2014).

Breast cancer, advanced, second-line endocrine-based combination therapy (relapsed or progressive on prior endocrine therapy; off-label combination): Adults (females, HER-2 negative): IM: 500 mg every 14 days for 3 doses, then every 28 days (in combination with palbociclib [and goserelin if pre- or peri-menopausal]); continue until disease progression or unacceptable toxicity (Turner 2015).

Dosage adjustment in renal impairment: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied). However, renal elimination of fulvestrant is negligible.

Dosage adjustment in hepatic impairment:

Mild impairment (Child-Pugh class A): No dosage adjustment is necessary.

Moderate impairment (Child-Pugh class B): Reduce initial doses and maintenance dose to 250 mg.

Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (use has not been evaluated).

Administration

For IM administration only. Administer 500 mg dose as two 5 mL IM injections (one in each buttocks) slowly over 1 to 2 minutes per injection.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Storage

Store in original carton at 2°C to 8°C (36°F to 46°F). Protect from light.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Adverse reactions reported with 500 mg dose.

>10%:

Endocrine & metabolic: Hot flushes (7% to 13%)

Hepatic: Alkaline phosphatase increased (>15%; grades 3/4: 1% to 2%), transaminases increased (>15%; grades 3/4: 1% to 2%)

Local: Injection site pain (12% to 14%)

Neuromuscular & skeletal: Joint disorders (14% to 19%)

1% to 10%:

Cardiovascular: Ischemic disorder (1%)

Central nervous system: Fatigue (8%), headache (8%)

Gastrointestinal: Nausea (10%), anorexia (6%), vomiting (6%), constipation (5%), weight gain (≤1%)

Genitourinary: Urinary tract infection (2% to 4%)

Neuromuscular & skeletal: Bone pain (9%), arthralgia (8%), back pain (8%), extremity pain (7%), musculoskeletal pain (6%), weakness (6%)

Respiratory: Cough (5%), dyspnea (4%)

<1% (Limited to important or life-threatening; reported with 250 mg or 500 mg dose): Angioedema, hepatitis, hypersensitivity reactions, leukopenia, liver failure, osteoporosis, thrombosis, vaginal bleeding

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: Hypersensitivity reactions, including urticaria and angioedema, have been reported.

Disease-related concerns:

• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia) and/or patients on anticoagulant therapy; bleeding/hematoma may occur from IM administration.

• Hepatic impairment: Exposure is increased and dosage adjustment is recommended in patients with moderate impairment. Safety and efficacy have not been established in severe impairment.

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.

Special handling:

• Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 1]).

Pregnancy Risk Factor

D

Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Fulvestrant is approved for use only in postmenopausal women. If used prior to confirmed menopause, women of reproductive potential should be advised not to become pregnant. Based on the mechanism of action, may cause fetal harm if administered during pregnancy.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience hot flashes, nausea, headache, back pain, constipation, lack of appetite, pharyngitis, or injection site pain or irritation. Have patient report immediately to prescriber paresthesia, depression, severe arthralgia, significant myalgia, considerable osteodynia, angina, dyspnea, intolerable asthenia, dysuria, or difficult urination (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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