Australia - English - Department of Health (Therapeutic Goods Administration)

interpharma pty ltd - fulvestrant, quantity: 50 mg/ml - injection, solution - excipient ingredients: benzyl alcohol; benzyl benzoate; castor oil; ethanol - fulvestrant ever pharma is indicated for the treatment of postmenopausal women with: ? hormone-receptor (hr) positive, human epidermal growth factor receptor 2(her2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy. ? hr positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

Australia - English - Department of Health (Therapeutic Goods Administration)

accord healthcare pty ltd - fulvestrant, quantity: 250 mg - injection, solution - excipient ingredients: benzyl alcohol; castor oil; benzyl benzoate; ethanol - fulvestrant accord is indicated for the treatment of postmenopausal women with: ? hormone-receptor (hr) positive, human epidermal growth factor receptor 2 (her2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy. ? hr positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

Australia - English - Department of Health (Therapeutic Goods Administration)

aft pharmaceuticals pty ltd - fulvestrant, quantity: 250 mg - injection, solution - excipient ingredients: ethanol; benzyl alcohol; benzyl benzoate; castor oil - fulvestrant-aft is indicated for the treatment of postmenopausal women with:,? hormone receptor (hr) positive, human epidermal growth factor receptor 2 (her2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy.,? hr positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

Australia - English - Department of Health (Therapeutic Goods Administration)

sandoz pty ltd - fulvestrant, quantity: 250 mg - injection, solution - excipient ingredients: castor oil; benzyl alcohol; benzyl benzoate; ethanol - fulvestrant sandoz is indicated for the treatment of postmenopausal women with: ? hormone receptor (hr) positive, human epidermal growth factor receptor 2 (her2) negative, locally advanced or metastatic breast cancer who have not been previously treated with endocrine therapy. ? hr positive, locally advanced or metastatic breast cancer who have progressive disease following prior endocrine (anti-oestrogen or aromatase inhibitor) therapy.

United States - English - NLM (National Library of Medicine)

fresenius kabi usa, llc - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥ 0.1 mg/kg/day (6% of the human recommended dose based on mg/m2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥ 0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant injection, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the last dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant injection can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant injection may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change=-0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change=-1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (cmin,ss ) and aucss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant in study 0021 and study 0020, respectively. fulvestrant is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter- acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant injection 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2) and warnings and precautions (5.2)]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

European Union - English - EMA (European Medicines Agency)

mylan pharmaceuticals limited - fulvestrant - breast neoplasms - endocrine therapy - fulvestrant is indicated for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women:not previously treated with endocrine therapy, orwith disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on antiestrogen therapy.

United States - English - NLM (National Library of Medicine)

athenex pharmaceutical division, llc. - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant injection [see adverse reactions ( 6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology ( 12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m 2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m 2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m 2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m 2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m 2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m 2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m 2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m 2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant can cause fetal harm when administered to a pregnant woman [see use in specific populations ( 8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology ( 13.1)] . safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change = -0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change = -1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant injection. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant injection. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (c min,ss ) and auc ss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant injection in study 0021 and study 0020, respectively. fulvestrant is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant injection has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration ( 2.2) and warnings and precautions ( 5.2)] . negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

United States - English - NLM (National Library of Medicine)

amneal pharmaceuticals llc - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data]. because of the potential for serious adverse reactions in breastfed infants from fulvestrant, advise a lactating woman not to breastfeed during treatment with fulvestrant and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant. contraception females fulvestrant can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients’ baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change = -0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change = -1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady-state trough concentration (cmin,ss ) and aucss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant in study 0021 and study 0020, respectively. fulvestrant is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p = 0.012). fulvestrant has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2)  and  warnings and precautions (5.2)]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

United States - English - NLM (National Library of Medicine)

northstar rx llc - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant injection [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)]. there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m2 , respectively [see data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant injection, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant injection can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant injection may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian or local consultant. all measurements during the study period were collected prospectively. patients' baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change=-0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change=-1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant injection on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant injection. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant injection. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (cmin,ss ) and aucss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant injection 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant injection in study 0021 and study 0020, respectively. fulvestrant injection is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n=7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p=0.012). fulvestrant injection has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant injection 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2) and warnings and precautions (5.2)]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.

United States - English - NLM (National Library of Medicine)

accord healthcare inc. - fulvestrant (unii: 22x328qoc4) (fulvestrant - unii:22x328qoc4) - monotherapy fulvestrant injection is indicated for the treatment of: - hormone receptor (hr)-positive, human epidermal growth factor receptor 2 (her2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or - hr-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. combination therapy fulvestrant injection is indicated for the treatment of: - hr-positive, her2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. - hr-positive, her2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. fulvestrant injection is contraindicated in patients with a known hypersensitivity to the drug or to any of its components. hypersensitivity reactions, including urticaria and angioedema, have been reported in association with fulvestrant injection [see adverse reactions (6.2)]. risk summary based on findings from animal studies and its mechanism of action, fulvestrant injection can cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no available data in pregnant women to inform the drug-associated risk. in animal reproduction studies, administration of fulvestrant to pregnant rats and rabbits during organogenesis caused embryo-fetal toxicity, including skeletal malformations and fetal loss, at daily doses that were 6% and 30% of the maximum recommended human dose based on mg/m 2 , respectively [see data]. advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data administration of fulvestrant to rats prior to and up to implantation caused embryonic loss at daily doses that were 0.6% of the daily maximum recommended human dose based on mg/m 2 . when fulvestrant was administered to pregnant rats during the period of organogenesis, intramuscular doses ≥0.1 mg/kg/day (6% of the human recommended dose based on mg/m 2 ) caused effects on embryo-fetal development consistent with its antiestrogenic activity. fulvestrant caused an increased incidence of fetal abnormalities in rats (tarsal flexure of the hind paw at 2 mg/kg/day; equivalent to the human dose based on mg/m 2 ) and non-ossification of the odontoid and ventral tubercle of the first cervical vertebra at doses ≥0.1 mg/kg/day. fulvestrant administered at 2 mg/kg/day caused fetal loss. when administered to pregnant rabbits during the period of organogenesis, fulvestrant caused pregnancy loss at an intramuscular dose of 1 mg/kg/day (equivalent to the human dose based on mg/m 2 ). further, at 0.25 mg/kg/day (30% the human dose based on mg/m 2 ), fulvestrant caused increases in placental weight and post-implantation loss in rabbits. fulvestrant was associated with an increased incidence of fetal variations in rabbits (backwards displacement of the pelvic girdle, and 27 pre-sacral vertebrae at 0.25 mg/kg/day; 30% the human dose based on mg/m 2 ) when administered during the period of organogenesis. risk summary there is no information regarding the presence of fulvestrant in human milk, nor of its effects on milk production or breastfed infant. fulvestrant can be detected in rat milk [see data] . because of the potential for serious adverse reactions in breastfed infants from fulvestrant injection, advise a lactating woman not to breastfeed during treatment with fulvestrant injection and for one year after the final dose. data levels of fulvestrant were approximately 12-fold higher in milk than in plasma after exposure of lactating rats to a dose of 2 mg/kg. drug exposure in rodent pups from fulvestrant-treated lactating dams was estimated as 10% of the administered dose. in a study in rats of fulvestrant at 10 mg/kg given twice or 15 mg/kg given once (less than the recommended human dose based on mg/m 2 ) during lactation, offspring survival was slightly reduced. pregnancy testing pregnancy testing is recommended for females of reproductive potential within seven days prior to initiating fulvestrant injection. contraception females fulvestrant injection can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . advise females of reproductive potential to use effective contraception during treatment and for one year after the last dose. infertility based on animal studies, fulvestrant injection may impair fertility in females and males of reproductive potential. the effects of fulvestrant on fertility were reversible in female rats [see nonclinical toxicology (13.1)]. safety and effectiveness in pediatric patients have not been established. a multi-center, single-arm, open-label, study of fulvestrant was conducted in 30 girls with mccune-albright syndrome (mas) associated with progressive precocious puberty (ppp). the median age at informed consent was 6 years old (range: 1 to 8). the first 10 patients initially received fulvestrant 2 mg/kg. based on pk data from the first 6 patients, all 10 patients receiving 2 mg/kg were escalated to a dose of 4 mg/kg and all other patients received 4 mg/kg from study entry. baseline measurements for vaginal bleeding days, bone age, growth velocity, and tanner staging for at least 6 months prior to study entry were provided retrospectively by the parent, guardian, or local consultant. all measurements during the study period were collected prospectively. patients’ baseline characteristics included the following: a mean ± sd chronological age of 5.9 ± 1.8 years; a mean rate of bone age advancement (change in bone age in years divided by change in chronological age in years) of 2.0 ± 1.03; and a mean growth velocity z-score of 2.4 ± 3.26. twenty-nine of 30 patients completed the 12-month study period. the following results were observed: 35% (95% ci: 16%, 57%) of the 23 patients with baseline vaginal bleeding experienced a complete cessation of vaginal bleeding on-treatment (month 0 to 12); a reduction in the rate of bone age advancement during the 12-month study period compared to baseline (mean change = -0.9 [95% ci: -1.4, -0.4]); and a reduction in mean growth velocity z-score on-treatment compared to baseline (mean change = -1.1 [95% ci: -2.7, 0.4]). there were no clinically meaningful changes in median tanner stage (breast or pubic), mean uterine volume, or mean ovarian volume, or predicted adult height (pah) on-treatment compared to baseline. the effect of fulvestrant injection on bone mineral density in children has not been studied and is not known. eight patients (27%) experienced adverse reactions that were considered possibly related to fulvestrant injection. these included injection site reactions (inflammation, pain, hematoma, pruritus, rash), abdominal pain, contusion, tachycardia, hot flash, extremity pain, and vomiting. nine (30%) patients reported an sae, none of which were considered related to fulvestrant injection. no patients discontinued study treatment due to an ae and no patients died. pharmacokinetics the pharmacokinetics of fulvestrant was characterized using a population pharmacokinetic analysis with sparse samples per patient obtained from 30 female pediatric patients aged 1 to 8 years with ppp associated with mas. pharmacokinetic data from 294 postmenopausal women with breast cancer who received 125 or 250 mg monthly dosing regimen were also included in the analysis. in these pediatric patients receiving 4 mg/kg monthly intramuscular dose of fulvestrant, the geometric mean (sd) cl/f was 444 (165) ml/min which was 32% lower than adults. the geometric mean (sd) steady state trough concentration (c min,ss ) and auc ss was 4.19 (0.87) ng/ml and 3680 (1020) ng*hr/ml, respectively. for fulvestrant injection 250 mg, when tumor response was considered by age, objective responses were seen in 22% and 24% of patients under 65 years of age and in 11% and 16% of patients 65 years of age and older, who were treated with fulvestrant injection in study 0021 and study 0020, respectively. fulvestrant injection is metabolized primarily in the liver. the pharmacokinetics of fulvestrant were evaluated after a single dose of 100 mg in subjects with mild and moderate hepatic impairment and normal hepatic function (n = 7 subjects/group), using a shorter-acting intramuscular injection formulation. subjects with mild hepatic impairment (child-pugh class a) had comparable mean auc and clearance values to those with normal hepatic function. in subjects with moderate hepatic impairment (child-pugh class b), the average auc of fulvestrant increased by 70% compared to patients with normal hepatic function. auc was positively correlated with total bilirubin concentration (p = 0.012). fulvestrant injection has not been studied in patients with severe hepatic impairment (child-pugh class c). a dose of fulvestrant injection 250 mg is recommended in patients with moderate hepatic impairment (child-pugh class b) [see dosage and administration (2.2)and warnings and precautions (5.2) ]. negligible amounts of fulvestrant are eliminated in urine; therefore, a study in patients with renal impairment was not conducted. in the advanced breast cancer trials, fulvestrant concentrations in women with estimated creatinine clearance as low as 30 ml/min were similar to women with normal creatinine.