Kanada - angličtina - Health Canada

mint pharmaceuticals inc - anastrozole - tablet - 1mg - anastrozole 1mg - antineoplastic agents

Kanada - angličtina - Health Canada

jamp pharma corporation - anastrozole - tablet - 1mg - anastrozole 1mg - antineoplastic agents

Kanada - angličtina - Health Canada

apotex inc - anastrozole - tablet - 1mg - anastrozole 1mg - antineoplastic agents

Kanada - angličtina - Health Canada

generic medical partners inc - anastrozole - tablet - 1mg - anastrozole 1mg - antineoplastic agents

Kanada - angličtina - Health Canada

cellchem pharmaceuticals inc. - anastrozole - tablet - 1mg - anastrozole 1mg - antineoplastic agents

Spojené státy - angličtina - NLM (National Library of Medicine)

northwind pharmaceuticals, llc - anastrozole (unii: 2z07myw1az) (anastrozole - unii:2z07myw1az) - anastrozole 1 mg - ​1.1 adjuvant treatment anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. 1.2 first-line treatment anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. 1.3 second-line treatment anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. patients with er-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. 4.1 pregnancy and premenopausal women anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. anastrozole is contraindicated in women who are or may become pregnant. there are no adequate and well-controlled studies in pregnant women using a

Spojené státy - angličtina - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - anastrozole (unii: 2z07myw1az) (anastrozole - unii:2z07myw1az) - anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. patients with er-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. hypersensitivity anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. observed reactions include anaphylaxis, angioedema, and urticaria [see adverse reactions ( 6.2)]. risk summary based on findings from animal studies and its mechanism of action, anastrozole may cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no studies of anastrozole use in pregnant women. anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (auc). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis. advise pregnant women and females of reproductive potential of the potential risk to a fetus. the 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 in animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively, (about 1 and 1/3 the recommended human dose on a mg/m 2 basis, respectively). in both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre-and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). in rats, these effects were dose related, and placental weights were significantly increased at doses equal to or greater than 0.1 mg/kg/day. fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses of 1 mg/kg/day that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (auc 0-24hr 9 times higher). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m 2 basis). risk summary there are no data on the presence of anastrozole or its metabolites in human milk, or its effects on the breast-fed child or on milk production. because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in the breast-fed child from anastrozole, advise lactating women not to breastfeed during treatment with anastrozole and for 2 weeks after the last dose. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole. contraception females based on animal studies, anastrozole 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 with anastrozole and for at least 3 weeks after the last dose. infertility females based on studies in female animals, anastrozole may impair fertility in females of reproductive potential [see nonclinical toxicology (13.1)] . clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with mccune-albright syndrome and progressive precocious puberty. the efficacy of anastrozole in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with mccune-albright syndrome has not been demonstrated. gynecomastia study a randomized, double-blind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. patients were randomized to a daily regimen of either anastrozole 1 mg or placebo. after 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥50% reduction in gynecomastia (primary efficacy analysis). secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. serum estradiol concentrations at month 6 of treatment were reduced by 15.4% in the anastrozole group and 4.5% in the placebo group. adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the anastrozole-treated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% anastrozole and 2.7% placebo) and headache (7% anastrozole and 0% placebo); all other adverse reactions showed small differences between treatment groups. one patient treated with anastrozole discontinued the trial because of testicular enlargement. the mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm 3 in the anastrozole-treated patients and + 5.2 ± 8.0 cm 3 in the placebo group. mccune-albright syndrome study a multi-center, single-arm, open-label study was conducted in 28 girls with mccune-albright syndrome and progressive precocious puberty aged 2 to <10 years. all patients received a 1 mg daily dose of anastrozole. the trial duration was 12 months. patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) mccune-albright syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean tanner stage for breast of 2.7 ± 0.81. compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). there were no clinically significant changes in tanner staging,mean ovarian volume, mean uterine volume and mean predicted adult height. a small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in mccune-albright syndrome patients. five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole. these were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis. pharmacokinetics in pediatric patients following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. the mean (range) disposition parameters of anastrozole in pediatric patients were described by a cl/f of 1.54 l/h (0.77 to 4.53 l/h) and v/f of 98.4 l (50.7 to 330.0 l). the terminal elimination half-life was 46.8 h, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole was similar in boys with pubertal gynecomastia and girls with mccune- albright syndrome. in studies 0030 and 0027, about 50% of patients were 65 or older. patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. in studies 0004 and 0005, 50% of patients were 65 or older. response rates and time to progression were similar for the over 65 and younger patients. in the atac study, 45% of patients were 65 years of age or older. the efficacy of anastrozole compared to tamoxifen in patients who were 65 years or older (n=1413 for anastrozole and n=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% ci: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (n=1712 for anastrozole and n=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% ci: 0.67, 0.94]). the pharmacokinetics of anastrozole are not affected by age. since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. dosage adjustment in patients with renal impairment is not necessary [see dosage and administration ( 2.1) and clinical pharmacology ( 12.3)]. the plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. anastrozole has not been studied in patients with severe hepatic impairment [see dosage and administration ( 2.2) and clinical pharmacology ( 12.3)].

Spojené státy - angličtina - NLM (National Library of Medicine)

avkare - anastrozole (unii: 2z07myw1az) (anastrozole - unii:2z07myw1az) - anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. patients with er-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. hypersensitivity anastrozole tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. observed reactions include anaphylaxis, angioedema, and urticaria [ see adverse reactions ( 6.2) ]. risk summary based on findings from animal studies and its mechanism of action, anastrozole tablets may cause fetal harm when administered to a pregnant woman [see clinical pharmacology ( 12.1)] . there are no studies of anastrozole tablet use in pregnant women. anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (auc). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis. advise pregnant women and females of reproductive potential of the potential risk to a fetus. the 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 in animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively, (about 1 and 1/3 the recommended human dose on a mg/m 2 basis, respectively). in both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). in rats, these effects were dose related, and placental weights were significantly increased at doses equal to or greater than 0.1 mg/kg/day. fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses of 1 mg/kg/day that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (auc 0-24hr 9 times higher). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m 2 basis). risk summary there are no data on the presence of anastrozole or its metabolites in human milk, or its effects on the breast-fed child or on milk production. because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in the breast-fed child from anastrozole tablets, advise lactating women not to breastfeed during treatment with anastrozole tablets and for 2 weeks after the last dose. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole tablets. contraception females based on animal studies, anastrozole tablets 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 with anastrozole tablets and for at least 3 weeks after the last dose. infertility females based on studies in female animals, anastrozole tablets may impair fertility in females of reproductive potential [see nonclinical toxicology (13.1)]. clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with mccune-albright syndrome and progressive precocious puberty. the efficacy of anastrozole tablets in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with mccune-albright syndrome has not been demonstrated. a randomized, double-blind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. patients were randomized to a daily regimen of either anastrozole tablets 1 mg or placebo. after 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥50% reduction in gynecomastia (primary efficacy analysis). secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. serum estradiol concentrations at month 6 of treatment were reduced by 15.4% in the anastrozole group and 4.5% in the placebo group. adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the anastrozole-treated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% anastrozole and 2.7% placebo) and headache (7% anastrozole and 0% placebo); all other adverse reactions showed small differences between treatment groups. one patient treated with anastrozole tablets discontinued the trial because of testicular enlargement. the mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm 3 in the anastrozole-treated patients and + 5.2 ± 8.0 cm 3 in the placebo group. a multi-center, single-arm, open-label study was conducted in 28 girls with mccune-albright syndrome and progressive precocious puberty aged 2 to <10 years. all patients received a 1 mg daily dose of anastrozole tablets. the trial duration was 12 months. patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) mccune-albright syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean tanner stage for breast of 2.7 ± 0.81. compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). there were no clinically significant changes in tanner staging, mean ovarian volume, mean uterine volume and mean predicted adult height. a small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in mccune-albright syndrome patients. five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole tablets. these were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis. following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. the mean (range) disposition parameters of anastrozole in pediatric patients were described by a cl/f of 1.54 l/h (0.77 to 4.53 l/h) and v/f of 98.4 l (50.7 to 330.0 l). the terminal elimination half-life was 46.8 h, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole was similar in boys with pubertal gynecomastia and girls with mccune-albright syndrome. in studies 0030 and 0027, about 50% of patients were 65 or older. patients ≥65 years of age had moderately better tumor response and time to tumor progression than patients <65 years of age regardless of randomized treatment. in studies 0004 and 0005, 50% of patients were 65 or older. response rates and time to progression were similar for the over 65 and younger patients. in the atac study, 45% of patients were 65 years of age or older. the efficacy of anastrozole compared to tamoxifen in patients who were 65 years or older (n=1413 for anastrozole and n=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% ci: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (n=1712 for anastrozole and n=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% ci: 0.67, 0.94]). the pharmacokinetics of anastrozole are not affected by age. since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. dosage adjustment in patients with renal impairment is not necessary [ see dosage and administration ( 2.1) and clinical pharmacology ( 12.3) ]. the plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. anastrozole has not been studied in patients with severe hepatic impairment [ see dosage and administration ( 2.2) and clinical pharmacology ( 12.3) ].

Spojené státy - angličtina - NLM (National Library of Medicine)

nucare pharmaceuticals,inc. - anastrozole (unii: 2z07myw1az) (anastrozole - unii:2z07myw1az) - anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. patients with er-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. hypersensitivity anastrozole is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. observed reactions include anaphylaxis, angioedema, and urticaria [see adverse reactions ( 6.2)]. risk summary based on findings from animal studies and its mechanism of action, anastrozole may cause fetal harm when administered to a pregnant woman [see clinical pharmacology (12.1)] . there are no studies of anastrozole use in pregnant women. anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (auc). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis. advise pregnant women and females of reproductive potential of the potential risk to a fetus. the 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 in animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively, (about 1 and 1/3 the recommended human dose on a mg/m 2 basis, respectively). in both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre-and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). in rats, these effects were dose related, and placental weights were significantly increased at doses equal to or greater than 0.1 mg/kg/day. fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses of 1 mg/kg/day that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (auc 0-24hr 9 times higher). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m 2 basis). risk summary there are no data on the presence of anastrozole or its metabolites in human milk, or its effects on the breast-fed child or on milk production. because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in the breast-fed child from anastrozole, advise lactating women not to breastfeed during treatment with anastrozole and for 2 weeks after the last dose. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole. contraception females based on animal studies, anastrozole 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 with anastrozole and for at least 3 weeks after the last dose. infertility females based on studies in female animals, anastrozole may impair fertility in females of reproductive potential [see nonclinical toxicology (13.1)] . clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with mccune-albright syndrome and progressive precocious puberty. the efficacy of anastrozole in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with mccune-albright syndrome has not been demonstrated. gynecomastia study a randomized, double-blind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. patients were randomized to a daily regimen of either anastrozole 1 mg or placebo. after 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥50% reduction in gynecomastia (primary efficacy analysis). secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. serum estradiol concentrations at month 6 of treatment were reduced by 15.4% in the anastrozole group and 4.5% in the placebo group. adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the anastrozole-treated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% anastrozole and 2.7% placebo) and headache (7% anastrozole and 0% placebo); all other adverse reactions showed small differences between treatment groups. one patient treated with anastrozole discontinued the trial because of testicular enlargement. the mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm 3 in the anastrozole-treated patients and + 5.2 ± 8.0 cm 3 in the placebo group. mccune-albright syndrome study a multi-center, single-arm, open-label study was conducted in 28 girls with mccune-albright syndrome and progressive precocious puberty aged 2 to <10 years. all patients received a 1 mg daily dose of anastrozole. the trial duration was 12 months. patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) mccune-albright syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. patients’ baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean tanner stage for breast of 2.7 ± 0.81. compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). there were no clinically significant changes in tanner staging,mean ovarian volume, mean uterine volume and mean predicted adult height. a small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in mccune-albright syndrome patients. five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole. these were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis. pharmacokinetics in pediatric patients following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. the mean (range) disposition parameters of anastrozole in pediatric patients were described by a cl/f of 1.54 l/h (0.77 to 4.53 l/h) and v/f of 98.4 l (50.7 to 330.0 l). the terminal elimination half-life was 46.8 h, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole was similar in boys with pubertal gynecomastia and girls with mccune- albright syndrome. in studies 0030 and 0027, about 50% of patients were 65 or older. patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. in studies 0004 and 0005, 50% of patients were 65 or older. response rates and time to progression were similar for the over 65 and younger patients. in the atac study, 45% of patients were 65 years of age or older. the efficacy of anastrozole compared to tamoxifen in patients who were 65 years or older (n=1413 for anastrozole and n=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% ci: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (n=1712 for anastrozole and n=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% ci: 0.67, 0.94]). the pharmacokinetics of anastrozole are not affected by age. since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. dosage adjustment in patients with renal impairment is not necessary [see dosage and administration ( 2.1) and clinical pharmacology ( 12.3)]. the plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. anastrozole has not been studied in patients with severe hepatic impairment [see dosage and administration ( 2.2) and clinical pharmacology ( 12.3)].

Spojené státy - angličtina - NLM (National Library of Medicine)

pd-rx pharmaceuticals, inc. - anastrozole (unii: 2z07myw1az) (anastrozole - unii:2z07myw1az) - anastrozole tablets are indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer. anastrozole tablets are indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer. anastrozole tablets are indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. patients with er-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole tablets. hypersensitivity anastrozole tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. observed reactions include anaphylaxis, angioedema, and urticaria [see adverse reactions ( 6.2) ] . risk summary based on findings from animal studies and its mechanism of action, anastrozole tablets may cause fetal harm when administered to a pregnant woman [see   clinical pharmacology ( 12.1)]. there are no studies of anastrozole tablets use in pregnant women. anastrozole caused embryo-fetal toxicities in rats at maternal exposure that were 9 times the human clinical exposure, based on area under the curve (auc). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m 2 basis. advise pregnant women and females of reproductive potential of the potential risk to a fetus. the 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 in animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively, (about 1 and 1/3 the recommended human dose on a mg/m 2 basis, respectively). in both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre-and/ or post-implantation loss, increased resorption, and decreased numbers of live fetuses). in rats, these effects were dose related, and placental weights were significantly increased at doses equal to or greater than 0.1 mg/kg/day. fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses of 1 mg/kg/day that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (auc 0-24hr 9 times higher). in rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1.0 mg/kg/day (about 16 times the recommended human dose on a mg/m 2 basis). risk summary there are no data on the presence of anastrozole or its metabolites in human milk, or its effects on the breast-fed child or on milk production. because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in the breast-fed child from anastrozole tablets, advise lactating women not to breastfeed during treatment with anastrozole tablets and for 2 weeks after the last dose. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiation of anastrozole tablets. contraception females based on animal studies, anastrozole tablets 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 with anastrozole tablets and for at least 3 weeks after the last dose. infertility females based on studies in female animals, anastrozole tablets may impair fertility in females of reproductive potential [see nonclinical toxicology ( 13.1)]. clinical studies in pediatric patients included a placebo-controlled trial in pubertal boys of adolescent age with gynecomastia and a single-arm trial in girls with mccune-albright syndrome and progressive precocious puberty. the efficacy of anastrozole in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with mccune-albright syndrome has not been demonstrated. gynecomastia study a randomized, doubleblind, placebo-controlled, multi-center study enrolled 80 boys with pubertal gynecomastia aged 11 to 18 years. patients were randomized to a daily regimen of either anastrozole 1 mg or placebo. after 6 months of treatment there was no statistically significant difference in the percentage of patients who experienced a ≥ 50% reduction in gynecomastia (primary efficacy analysis). secondary efficacy analyses (absolute change in breast volume, the percentage of patients who had any reduction in the calculated volume of gynecomastia, breast pain resolution) were consistent with the primary efficacy analysis. serum estradiol concentrations at month 6 of treatment were reduced by 15.4% in the anastrozole group and 4.5% in the placebo group. adverse reactions that were assessed as treatment-related by the investigators occurred in 16.3% of the anastrozole-treated patients and 8.1% of the placebo-treated patients with the most frequent being acne (7% anastrozole and 2.7% placebo) and headache (7% anastrozole and 0% placebo); all other adverse reactions showed small differences between treatment groups. one patient treated with anastrozole discontinued the trial because of testicular enlargement. the mean baseline-subtracted change in testicular volume after 6 months of treatment was + 6.6 ± 7.9 cm3 in the anastrozole-treated patients and + 5.2 ± 8.0 cm3 in the placebo group. mccune-albright syndrome study a multi-center, single-arm, open-label study was conducted in 28 girls with mccune-albright syndrome and progressive precocious puberty aged 2 to < 10 years. all patients received a 1 mg daily dose of anastrozole. the trial duration was 12 months. patients were enrolled on the basis of a diagnosis of typical (27/28) or atypical (1/27) mccune-albright syndrome, precocious puberty, history of vaginal bleeding, and/or advanced bone age. patients' baseline characteristics included the following: a mean chronological age of 5.9 ± 2.0 years, a mean bone age of 8.6 ± 2.6 years, a mean growth rate of 7.9 ± 2.9 cm/year and a mean tanner stage for breast of 2.7 ± 0.81. compared to pre-treatment data there were no on-treatment statistically significant reductions in the frequency of vaginal bleeding days, or in the rate of increase of bone age (defined as a ratio between the change in bone age over the change of chronological age). there were no clinically significant changes in tanner staging, mean ovarian volume, mean uterine volume and mean predicted adult height. a small but statistically significant reduction of growth rate from 7.9 ± 2.9 cm/year to 6.5 ± 2.8 cm/year was observed but the absence of a control group precludes attribution of this effect to treatment or to other confounding factors such as variations in endogenous estrogen levels commonly seen in mccune-albright syndrome patients. five patients (18%) experienced adverse reactions that were considered possibly related to anastrozole. these were nausea, acne, pain in an extremity, increased alanine transaminase and aspartate transaminase, and allergic dermatitis. pharmacokinetics in pediatric patients following 1 mg once daily multiple administration in pediatric patients, the mean time to reach the maximum anastrozole concentration was 1 hr. the mean (range) disposition parameters of anastrozole in pediatric patients were described by a cl/f of 1.54 l/h (0.77 to 4.53 l/h) and v/f of 98.4 l (50.7 to 330.0 l). the terminal elimination half-life was 46.8 h, which was similar to that observed in postmenopausal women treated with anastrozole for breast cancer. based on a population pharmacokinetic analysis, the pharmacokinetics of anastrozole was similar in boys with pubertal gynecomastia and girls with mccune-albright syndrome. in studies 0030 and 0027, about 50% of patients were 65 or older. patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. in studies 0004 and 0005, 50% of patients were 65 or older. response rates and time to progression were similar for the over 65 and younger patients. in the atac study, 45% of patients were 65 years of age or older. the efficacy of anastrozole tablets compared to tamoxifen in patients who were 65 years or older (n=1413 for anastrozole tablets and n=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 [95% ci: 0.80, 1.08]) was less than efficacy observed in patients who were less than 65 years of age (n=1712 for anastrozole tablets and n=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 [95% ci: 0.67, 0.94]). the pharmacokinetics of anastrozole are not affected by age. since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. dosage adjustment in patients with renal impairment is not necessary [see dosage and administration ( 2.1) and clinical pharmacology ( 12.3)]. the plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. anastrozole tablets have not been studied in patients with severe hepatic impairment [see dosage and administration ( 2.2) and clinical pharmacology ( 12.3)].