Summary Of Exposure |
A) USES: In postmenopausal women, fulvestrant is indicated for the treatment of hormone receptor positive metastatic breast cancer that has progressed following antiestrogen therapy.
B) PHARMACOLOGY: Fulvestrant is a pure estrogen receptor antagonist that competes with endogenous estrogen for binding. The binding affinity of fulvestrant is comparable (89%) to that of estradiol. By binding to estrogen receptors, fulvestrant also down-regulates the estrogen receptor protein and reduces the cellular levels of estrogen receptors. Fulvestrant completely abates the transcription of estrogen receptor regulated genes and has no estrogen agonist activity. Fulvestrant has also shown efficacy in breast cancer through inhibition of cellular aromatase activity.
C) EPIDEMIOLOGY: Overdose is rare.
D) WITH THERAPEUTIC USE
1) COMMON: The most commonly reported adverse reactions following fulvestrant therapy, with an incidence greater than 5% during clinical trials, are nausea, vomiting, diarrhea, anorexia, constipation, abdominal pain, headache, back pain, vasodilation (hot flushes), fever, peripheral edema, hepatic enzyme elevation, bone pain, pain in extremity, musculoskeletal pain, arthralgia, fatigue, asthenia, dizziness, insomnia, paresthesia, depression, dyspnea, pharyngitis, cough, rash, sweating, and injection site reactions.
2) INFREQUENT: Other adverse effects that occurred less frequently with fulvestrant therapy include vertigo, myalgia, anemia, leukopenia, vaginal bleeding, hepatitis, liver failure, and hypersensitivity reactions (eg, angioedema and urticaria).
E) WITH POISONING/EXPOSURE
1) Fulvestrant overdose information is limited. No adverse effects were reported in male or female volunteers when intravenous fulvestrant was administered to achieve peak plasma concentrations 10-15 times those seen at therapeutic intramuscular doses. Mild (grade 1) side effects including headache, hot flushes, and gastrointestinal disturbances were seen in premenopausal women receiving one 750 mg fulvestrant intramuscular injection. It is anticipated that overdose effects are an extension of adverse effects following therapeutic administration.
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Vital Signs |
3.3.1) SUMMARY
A) WITH THERAPEUTIC USE 1) Fever was reported with fulvestrant therapy during clinical trials.
3.3.3) TEMPERATURE
A) WITH THERAPEUTIC USE a) FEVER: According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, fever was reported in 6.4% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) VASODILATATION 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, vasodilatation was reported in 17.7% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) In a double-blind, double-dummy randomized phase III trial comparing fulvestrant to tamoxifen, vasodilation was reported in 14.8% of patients randomized to fulvestrant (Vergote & Abram, 2006).
B) CHEST PAIN 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, chest pain was reported in 7.1% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) PERIPHERAL EDEMA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, peripheral edema was reported in 9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Respiratory |
3.6.2) CLINICAL EFFECTS
A) DYSPNEA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, dyspnea was reported in 14.9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, dyspnea was reported in 4.4% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 5.1% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
B) PHARYNGITIS 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, pharyngitis was reported in 16.1% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) COUGH 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, increased cough was reported in 10.4% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, cough was reported in 5.3% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 5.3% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) HEADACHE 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, headaches were reported in 15.4% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, headaches were reported in 7.8% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 6.7% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
2) WITH POISONING/EXPOSURE a) In a trial of premenopausal women receiving a single intramuscular injection of 750 mg fulvestrant, headache was reported in 30% (n=30) of participants (Young et al, 2008).
B) ASTHENIA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, asthenia was reported in 22.7% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, asthenia was reported in 5.8% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 6.1% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
c) In a double-blind, double-dummy randomized phase III trial comparing fulvestrant to tamoxifen, asthenia symptoms were reported in 19.4% of patients randomized to fulvestrant (Vergote & Abram, 2006).
C) PARESTHESIA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, paresthesia was reported in 6.4% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
D) DIZZINESS 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, dizziness was reported in 6.9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
E) INSOMNIA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, insomnia was reported in 6.9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
F) FEELING AGITATED 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, anxiety was reported in 5% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
G) CENTRAL NERVOUS SYSTEM DEPRESSION 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, depression was reported in 5.7% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
H) VERTIGO 1) WITH THERAPEUTIC USE a) Vertigo has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) NAUSEA AND VOMITING 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, nausea and vomiting were reported in 26% and 13%, respectively, of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, nausea and vomiting were reported in 9.7% and 6.1%, respectively, of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 13.6% and 5.6%, respectively, of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
c) In a double-blind, double-dummy randomized phase III trial comparing fulvestrant to tamoxifen, nausea was reported in 20.3% of patients randomized to fulvestrant (Vergote & Abram, 2006).
2) WITH POISONING/EXPOSURE a) In a trial of premenopausal women receiving a single intramuscular injection of 750 mg fulvestrant, nausea was reported in 17% (n=30) of participants (Young et al, 2008).
B) DIARRHEA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, diarrhea was reported in 12.3% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) CONSTIPATION 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, constipation was reported in 12.5% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, constipation was reported in 5% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 3.5% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
D) ABDOMINAL PAIN 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, abdominal pain was reported in 11.8% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
E) LOSS OF APPETITE 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, anorexia was reported in 9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, anorexia was reported in 6.1% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 3.7% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Hepatic |
3.9.2) CLINICAL EFFECTS
A) LIVER ENZYMES ABNORMAL 1) WITH THERAPEUTIC USE a) Increase from baseline of AST, ALT, or alkaline phosphatase levels by 1 or more Common Toxicity Criteria (CTC) grades was reported in more than 15% of patients in pooled analysis from clinical trials (n=1127) comparing fulvestrant 500 mg with fulvestrant 250 mg. Grade 3/4 increases were reported in 1% to 2% of patients. The incidence and severity of the increased enzymes were not dose-dependent (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) Increased gamma-glutamyl transferase levels have been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
B) INCREASED BILIRUBIN LEVEL 1) WITH THERAPEUTIC USE a) Increased bilirubin levels have been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) INFLAMMATORY DISEASE OF LIVER 1) WITH THERAPEUTIC USE a) Hepatitis has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
D) HEPATIC FAILURE 1) WITH THERAPEUTIC USE a) Liver failure has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) LEUKOPENIA 1) WITH THERAPEUTIC USE a) Leukopenia has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012).
B) ANEMIA 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, anemia was reported in 4.5% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) BLEEDING 1) WITH THERAPEUTIC USE a) VAGINAL BLEEDING has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant, and may occur primarily in patients during the first 6 weeks after changing from existing hormonal therapy to fulvestrant therapy (Prod Info FASLODEX(R) intramuscular injection, 2012).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) ERUPTION 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, rash was reported in 7.3% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
B) INJECTION SITE PAIN 1) WITH THERAPEUTIC USE a) Injection site reactions with mild, transient pain and inflammation have been reported with fulvestrant treatment in 7% of patients who received a single 5 mL injection and in 27% of patients who received two 2.5 mL injections (Prod Info FASLODEX(R) intramuscular injection, 2012).
b) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, injection site pain was reported in 10.9% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
c) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, injection site pain was reported in 11.6% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 9.1% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
C) SWEATING 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, sweating was reported in 5% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
D) FLUSHING 1) WITH THERAPEUTIC USE a) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, hot flashes were reported in 6.6% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 5.9% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) Hot flushes occurred in 19% to 24% of patients in two separate phase III trials (Curran & Wiseman, 2001).
2) WITH POISONING/EXPOSURE a) In a clinical trial of premenopausal women receiving a single intramuscular injection of 750 mg fulvestrant, hot flushes were reported in 23% (n=30) of participants (Young et al, 2008).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) BACKACHE 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, back pain was reported in 14.4% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, back pain was reported in 7.5% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 10.7% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
B) BONE PAIN 1) WITH THERAPEUTIC USE a) According to pooled data from 2 randomized controlled clinical trials comparing fulvestrant with anastrozole in post-menopausal women (median age, 64 years) with locally advanced or metastatic breast cancer who had disease progression following antiestrogen or progestin therapy for either advanced disease or as adjuvant treatment, bone pain was reported in 15.8% of patients treated with fulvestrant 250 mg IM monthly (n=423) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
b) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, bone pain, extremity pain, and musculoskeletal pain were reported in 9.4%, 6.9%, and 5.5%, respectively, of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 7.5%, 7%, and 3.2%, respectively, of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
c) In a double-blind, double-dummy randomized phase III trial comparing fulvestrant to tamoxifen, bone pain was reported in 13.9% of patients randomized to fulvestrant (Vergote & Abram, 2006).
C) JOINT PAIN 1) WITH THERAPEUTIC USE a) During a randomized, double-blind, controlled clinical trial in postmenopausal women (median age, 61 years) with advanced breast cancer and disease recurrence, on or after adjuvant endocrine therapy, or progression following endocrine therapy, arthralgia was reported in 8% of patients treated with fulvestrant 500 mg IM monthly (n=361) compared with 7.8% of those treated with fulvestrant 250 mg IM monthly (n=374) (Prod Info FASLODEX(R) intramuscular injection, 2012a).
D) MUSCLE PAIN 1) WITH THERAPEUTIC USE a) Myalgia has been reported in less than 1% of patients during postmarketing surveillance of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) HYPERSENSITIVITY REACTION 1) WITH THERAPEUTIC USE a) Hypersensitivity reactions, including angioedema and urticaria, have been reported in less than 1% of patients during postmarketing surveillance with the use of fulvestrant (Prod Info FASLODEX(R) intramuscular injection, 2012a).
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Reproductive |
3.20.1) SUMMARY
A) In rat studies, there were increased incidences of fetal abnormalities (tarsal flexure of hind paw and non-ossification of odontoid and ventral tubercle of C1 vertebra) following maternal exposure. Rabbit studies demonstrated failure to maintain pregnancy at doses twice the human dose based on body surface area.
3.20.2) TERATOGENICITY
A) ANIMAL STUDIES 1) Increased fetal skeletal variations were reported with doses 30% of the human dose (Prod Info FASLODEX(R) intramuscular injection, 2016).
3.20.3) EFFECTS IN PREGNANCY
A) RISK SUMMARY 1) Do not administer to a pregnant woman. If pregnancy occurs, apprise patient of potential for fetal harm (Prod Info FASLODEX(R) intramuscular injection, 2016).
B) CONTRACEPTION 1) Female patients of reproductive potential should use adequate contraception during treatment and for at least one year after discontinuation (Prod Info FASLODEX(R) intramuscular injection, 2016).
C) PREGNANCY TESTING 1) Perform pregnancy testing in female patients of reproductive potential 7 days prior to initiation of treatment (Prod Info FASLODEX(R) intramuscular injection, 2016).
D) ANIMAL STUDIES 1) During animal studies, administration of fulvestrant prior to and up to implantation resulted in embryonic loss with doses up to 0.6% of the daily recommended human dose. Effects on embryofetal development consistent with antiestrogenic activity was observed with administration of IM fulvestrant at doses up to 6% of the human recommended dose (Prod Info FASLODEX(R) intramuscular injection, 2016).
2) Pregnancy loss was reported with IM fulvestrant doses equivalent to the human dose and increase in placental weight and post-implantation loss were reported with doses 30% of the human dose (Prod Info FASLODEX(R) intramuscular injection, 2016).
3.20.4) EFFECTS DURING BREAST-FEEDING
A) LACK OF INFORMATION 1) It is not known if fulvestrant is excreted into human milk (Prod Info FASLODEX(R) intramuscular injection, 2016).
B) BREAST MILK 1) Do not breastfeed while taking this drug and for at least one year after discontinuation (Prod Info FASLODEX(R) intramuscular injection, 2016).
C) ANIMAL STUDIES 1) Fulvestrant levels were approximately 12-fold higher in milk than in plasma after exposure in lactating animals at a dose of 2 mg/kg. Drug exposure in exposed offspring were estimated at 10% of the administered dose. Offspring survival was slightly reduced following treatment with fulvestrant 10 mg/kg or 15 mg/kg during lactation (Prod Info FASLODEX(R) intramuscular injection, 2016).
3.20.5) FERTILITY
A) ANIMAL STUDIES 1) A reduction in fertility and embryonic survival was reported with fulvestrant at doses 0.6% of the human recommended dose in female animals. No adverse effects on female fertility or embryonic survival were observed with doses at 0.06% times the recommended dose. Restoration values were similar to controls following a 29-day withdrawal period. In male animals, a loss of spermatozoa from seminiferous tubules, seminiferous tubular atrophy, and degenerative changes in the epididymides were reported with doses up to 15 mg/kg. Recovery was not reported 20 weeks after cessation (Prod Info FASLODEX(R) intramuscular injection, 2016).
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Carcinogenicity |
3.21.4) ANIMAL STUDIES
A) CARCINOMA 1) RATS: A two-year carcinogenicity study demonstrated an increased incidence of benign ovarian granulosa cell tumors in female rats exposed to IM fulvestrant at 10 mg/rat/15 days; a 3-fold increase in systemic exposure relative to that seen in women at the recommended dose of 500 mg/month. The same study showed an increased incidence of testicular Leydig cell tumors in male rats exposed to IM fulvestrant at 15 mg/rat/30 days (corresponds to a 0.8-fold increase in systemic exposure relative to that seen in women at the recommended dose of 500 mg/month) (Prod Info FASLODEX(R) intramuscular injection, 2012).
2) MICE: A two-year carcinogenicity study demonstrated an increased incidence of sex cord stromal tumors (benign and malignant) in the ovary of female mice exposed to oral fulvestrant at 150 and 500 mg/kg/day; an 8.4- and 18-fold increase in systemic exposure relative to that seen in women at the recommended dose of 500 mg/month, respectively (Prod Info FASLODEX(R) intramuscular injection, 2012).
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Genotoxicity |
A) Fulvestrant was not mutagenic or clastogenic according to the bacterial mutation assay of Salmonella typhimurium and Escherichia coli, the in vitro cytogenetics study in human lymphocytes, the mouse lymphoma cell mutation assay, and the in vivo rat micronucleus test.
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