- Injection, solution 50 mg/mL
Fulvestrant competitively binds to the estrogen receptor and downregulates the estrogen receptor protein in human breast cancer cells.
C max is 28 ng/mL, C min is 12.2 ng/mL, and AUC is 13,100 ng•h/mL at steady state.
Apparent Vd at steady state is 3 to 5 L/kg. Protein binding is 99%.
Metabolism takes place in the liver by oxidation via CYP3A4 isoenzyme, aromatic hydroxylation, and conjugation with glucuronic acid and/or sulphate.
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 PopulationsRenal Function Impairment
Fulvestrant concentrations in women with estimated creatinine clearance as low as 30 mL/min were similar to women with normal creatinine.Hepatic Function Impairment
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.Elderly
There were no pharmacokinetic differences observed related to age (range, 33 to 89 y of age).Children
The pharmacokinetics have not been evaluated in children.Gender
There were no pharmacokinetic differences between men and women.Race
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.
Hypersensitivity to the drug or any component of the product.
Dosage and AdministrationAdults
IM 500 mg on days 1, 15, and 29, and once monthly thereafter.Hepatic function impairment
IM 250 mg in patients with moderate hepatic impairment (Child-Pugh class B) on days 1, 15, and 29, and once monthly thereafter.
- For slow IM administration only (1 to 2 minutes per injection).
- Administer as two 5 mL injections, one in each buttock.
Store prefilled syringes in refrigerator (36° to 46°F).
Drug InteractionsDisulfiram, metronidazole
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.
Vasodilation (18%); hot flash (7%); thromboembolic phenomena (postmarketing).
Asthenia (23%); headache (15%); fatigue (8%); dizziness, insomnia (7%); asthenia, depression, paresthesia (6%); anxiety (5%).
Rash (7%); sweating (5%).
Nausea (26%); constipation, vomiting (13%); abdominal pain, diarrhea (12%); anorexia (9%).
UTI (6%); vaginal bleeding (postmarketing).
Anemia (5%); leukopenia (postmarketing).
Increased alkaline phosphatase, ALT, AST (more than 15%).
Hypersensitivity reactions, including angioedema and urticaria (postmarketing).
Injection-site reactions with mild transient pain and inflammation (27%); injection-site pain (12%).
Bone pain (16%); back pain (14%); arthralgia (8%); musculoskeletal pain (6%); arthritis (3%).
Dyspnea (15%); increased cough (10%); cough (5%).
Pain (19%); pelvic pain (10%); peripheral edema (9%); chest pain, flu syndrome, pain in extremity (7%); fever (6%).
Category D . May cause fetal harm when administered to a pregnant woman.
Safety and efficacy not established.
Use with caution in patients with bleeding diatheses, thrombocytopenia, or anticoagulant use.
- 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).
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