Fulvestrant

Pronunciation: ful-VES-trant
Class: Antiestrogen

Trade Names

Faslodex
- Injection, solution 50 mg/mL

Pharmacology

Fulvestrant competitively binds to the estrogen receptor and downregulates the estrogen receptor protein in human breast cancer cells.

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Pharmacokinetics

Absorption

C _max is 28 ng/mL, C _min is 12.2 ng/mL, and AUC is 13,100 ng•h/mL at steady state.

Distribution

Apparent Vd at steady state is 3 to 5 L/kg. Protein binding is 99%.

Metabolism

Metabolism takes place in the liver by oxidation via CYP3A4 isoenzyme, aromatic hydroxylation, and conjugation with glucuronic acid and/or sulphate.

Elimination

The half-life is approximately 40 days. Cl is approximately 690 mL/min. Fulvestrant is cleared by the hepatobiliary route; renal elimination is less than 1%. It is primarily excreted in the feces (approximately 90%).

Special Populations

Fulvestrant concentrations in women with estimated creatinine clearance as low as 30 mL/min were similar to women with normal creatinine.

In moderate hepatic impairment (Child-Pugh class B), the average AUC of fulvestrant increased by 70% compared with patients with healthy hepatic function. Fulvestrant has not been studied in patients with severe hepatic impairment.

There were no pharmacokinetic differences observed related to age (range, 33 to 89 y of age).

The pharmacokinetics have not been evaluated in children.

There were no pharmacokinetic differences between men and women.

No differences in pharmacokinetics were observed among white, black, and Hispanic patient populations.

Indications and Usage

Treatment of hormone receptor–positive metastatic breast cancer in postmenopausal women with disease progression following antiestrogen therapy.

Contraindications

Hypersensitivity to the drug or any component of the product.

Dosage and Administration

IM 500 mg on days 1, 15, and 29, and once monthly thereafter.

IM 250 mg in patients with moderate hepatic impairment (Child-Pugh class B) on days 1, 15, and 29, and once monthly thereafter.

General Advice

• For slow IM administration only (1 to 2 minutes per injection).
• Administer as two 5 mL injections, one in each buttock.

Storage/Stability

Store prefilled syringes in refrigerator (36° to 46°F).

Drug Interactions

Because fulvestrant injection contains alcohol, patients receiving disulfiram or metronidazole may experience an acute alcohol intolerance reaction if fulvestrant is coadministered. Avoid fulvestrant administration to patients receiving disulfiram or metronidazole.

Adverse Reactions

Cardiovascular

Vasodilation (18%); hot flash (7%); thromboembolic phenomena (postmarketing).

CNS

Asthenia (23%); headache (15%); fatigue (8%); dizziness, insomnia (7%); asthenia, depression, paresthesia (6%); anxiety (5%).

Dermatologic

Rash (7%); sweating (5%).

EENT

Pharyngitis (16%).

GI

Nausea (26%); constipation, vomiting (13%); abdominal pain, diarrhea (12%); anorexia (9%).

Genitourinary

UTI (6%); vaginal bleeding (postmarketing).

Hematologic

Anemia (5%); leukopenia (postmarketing).

Hepatic

Increased alkaline phosphatase, ALT, AST (more than 15%).

Hypersensitivity

Hypersensitivity reactions, including angioedema and urticaria (postmarketing).

Local

Injection-site reactions with mild transient pain and inflammation (27%); injection-site pain (12%).

Musculoskeletal

Bone pain (16%); back pain (14%); arthralgia (8%); musculoskeletal pain (6%); arthritis (3%).

Respiratory

Dyspnea (15%); increased cough (10%); cough (5%).

Miscellaneous

Pain (19%); pelvic pain (10%); peripheral edema (9%); chest pain, flu syndrome, pain in extremity (7%); fever (6%).

Precautions

Pregnancy

Category D . May cause fetal harm when administered to a pregnant woman.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Bleeding tendencies

Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.

Patient Information

• Advise patient that medication will be prepared and administered by health care provider in a health care setting on a monthly basis.
• Instruct patient to inform health care provider if any of the following symptoms occur: intolerable nausea, vomiting, constipation, diarrhea, stomach pain, headache, hot flushes, injection-site pain or inflammation.
• Advise women of childbearing potential not to become pregnant while receiving fulvestrant and that this drug may cause fetal harm when administered to a pregnant woman.
• Inform patients that fulvestrant is administered by IM injection and should be used with caution in patients with bleeding tendencies or decreased platelet count, or in patients receiving anticoagulants (eg, warfarin).

Copyright © 2009 Wolters Kluwer Health.