ישראל - אנגלית - Ministry of Health

novartis israel ltd - octreotide - powder and solvent for suspension for injection - octreotide 10 mg - octreotide - octreotide - treatment of acromegaly in: patients already adequately controlled on standard doses of sandostatin s.c. patients in whom surgery or radiotherapy are inappropriate or ineffective, or who are in the latency period before radiotherapy becomes fully effective. endocrine gastro-entero- pancreatic (gep) tumors, carcinoid tumors.

האיחוד האירופי - אנגלית - EMA (European Medicines Agency)

schering-plough europe - interferon alfa-2b - hepatitis c, chronic; hepatitis b, chronic - immunostimulants, - chronic hepatitis b: treatment of adult patients with chronic hepatitis b associated with evidence of hepatitis b viral replication (presence of hbv-dna and hbeag), elevated alanine aminotransferase (alt) and histologically proven active liver inflammation and/or fibrosis.chronic hepatitis c:adult patients:introna is indicated for the treatment of adult patients with chronic hepatitis c who have elevated transaminases without liver decompensation and who are positive for serum hcv-rna or anti-hcv (see section 4.4).the best way to use introna in this indication is in combination with ribavirin.chidren and adolescents:introna is intended for use, in a combination regimen with ribavirin, for the treatment of children and adolescents 3 years of age and older, who have chronic hepatitis c, not previously treated, without liver decompensation, and who are positive for serum hcv-rna. the decision to treat should be made on a case by case basis, taking into account any evidence of disease progression such as hepatic inflammation and fibrosis, as well as prognostic factors for response, hcv genotype and viral load. the expected benefit of treatment should be weighed against the safety findings observed for paediatric subjects in the clinical trials (see sections 4.4, 4.8 and 5.1).

ארצות הברית - אנגלית - NLM (National Library of Medicine)

mitsubishi tanabe pharma america, inc. - edaravone (unii: s798v6yjrp) (edaravone - unii:s798v6yjrp) - edaravone 30 mg in 100 ml - radicava and radicava ors are indicated for the treatment of amyotrophic lateral sclerosis (als). radicava and radicava ors are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in this product. hypersensitivity reactions and anaphylactic reactions have occurred [see warnings and precautions (5.1 , 5.2 )]. risk summary there are no adequate data on the developmental risk associated with the use of radicava or radicava ors in pregnant women. in animal studies, administration of edaravone to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. most of these effects occurred at doses that were also associated with maternal toxicity (see animal data ) . 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. the background risk for major birth defects and miscarriage in patients with als is unknown. data animal data in rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses. in dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. maternal toxicity was also observed at the highest dose tested. there were no adverse effects on reproductive function in the offspring. a no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg for radicava on a body surface area (mg/m2 ) basis. in rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. the higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (rhd) for radicava on a body surface area (mg/m2 ) basis. the effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from gd 17 throughout lactation, were assessed in two studies. in the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. in the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested. reproduction function in offspring was not affected in either study. maternal toxicity was evident in both studies at all but the lowest dose tested. the no-effect dose for developmental toxicity (3 mg/kg/day) is less than the rhd on a mg/m2 basis. reproductive and developmental toxicology studies of edaravone using the oral route have not been conducted risk summary there are no data on the presence of edaravone in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. edaravone and its metabolites are excreted in the milk of lactating rats. the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for radicava and radicava ors and any potential adverse effects on the breastfed infant from radicava and radicava ors or from the underlying maternal condition. safety and effectiveness of radicava or radicava ors in pediatric patients have not been established of the 184 patients with als who received radicava in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. no overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

dr. reddy's laboratories limited - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride 5 mg - finasteride tablets are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to: -  improve symptoms - reduce the risk of acute urinary retention -  reduce the risk of the need for surgery including transurethral resection of the prostate (turp) and prostatectomy. finasteride tablets administered in combination with the alpha-blocker doxazosin are indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥4 point increase in american urological association (aua) symptom score). finasteride tablets are not approved for the prevention of prostate cancer. finasteride tablets are contraindicated in the following: - hypersensitivity to any component of this medication. - pregnancy. finasteride use is contraindicated in females when they are or may potentially be pregnant. because of the ability of type ii 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (dht), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant females who receives finasteride. if this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant females should be apprised of the potential hazard to the male fetus. [see also warnings and precautions (5.3) , use in specific populations (8.1) , and how supplied/storage and handling (16) ]. in female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. risk summary finasteride is contraindicated in pregnant females and not indicated for use in females. based onanimal studies and the mechanism of action, finasteride may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female [see warnings and precautions (5.3) andclinical pharmacology (12.1) ]. in an embryo-fetal development study in rats, there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring of pregnant rats administered oral finasteride during the period of major organogenesis at doses approximately 0.1 to 86 times the maximum recommended human dose (mrhd) of 5 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day). decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development were also observed in male offspring at oral maternal doses approximately 0.03 times the mrhd (based on auc at animal dose of 0.03 mg/kg/day), along with decreased anogenital distance in male offspring at oral maternal doses approximately 0.003 times the mrhd (based on auc at animal dose of 0.003 mg/kg/day). finasteride is a type ii 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (dht), a hormone necessary for normal development of male genitalia. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus. abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (dht) is inhibited by 5α-reductase inhibitors. these outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. females could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride. with regard to finasteride exposure through the skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. females who are pregnant or may potentially be pregnant should not handle crushed or broken finasteride tablets because of possible exposure of a male fetus. with regard to potential finasteride exposure through semen, three studies have been conducted that measured finasteride concentrations in semen in men receiving finasteride 5 mg/day. in these studies the highest amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 mcg) that had no effect on circulating dht levels in men [see data and clinical pharmacology (12.3) ]. data human data in 2 studies of healthy subjects (n=69) receiving finasteride 5 mg/day for 6 to 24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/ml) to 10.54 ng/ml. in an earlier study using a less sensitive assay, finasteride concentrations in semen of 16 subjects receiving finasteride 5 mg/day ranged from undetectable (<1 ng/ml) to 21 ng/ml. using the highest semen level measured and assuming 100% absorption would be up to 105 ng per day, which is 50- to 100-fold less than the dose of finasteride (5 mcg) that had no effect on circulating dht levels in men [see clinical pharmacology (12.3)]. animal data in an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). at maternal doses of oral finasteride approximately 0.1 to 86 times the maximum recommended human dose (mrhd) of 5 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. exposure multiples were estimated using data from nonpregnant rats. days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. at oral maternal doses approximately 0.03 times the mrhd (based on auc at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.003 times the mrhd (based on auc at animal dose of 0.003 mg/kg/day). no abnormalities were observed in female offspring at any maternal dose of finasteride. no developmental abnormalities were observed in the offspring of untreated females mated with finasteride treated male rats that received approximately 61 times the mrhd (based on auc at animal dose of 80 mg/kg/day). slightly decreased fertility was observed in male offspring after administration of about 3 times the mrhd (based on auc at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. no effects on fertility were seen in female offspring under these conditions. no evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal oral doses up to 100 mg/kg /day, (finasteride exposure levels were not measured in rabbits). however, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. the fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/ml or about 143 times the highest estimated exposure of pregnant females to finasteride from semen of men taking 5 mg/day) resulted in no abnormalities in male fetuses. in confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of finasteride from semen of men taking 5 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. no other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. risk summary finasteride tablets are not indicated for use in females. infertility females finasteride tablets are not indicated for use in females. males treatment with finasteride tablets for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or ph. a 0.6 ml (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed. these parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks [see warnings and precautions (5.5) ]. there have been postmarketing reports of male infertility and/or poor seminal quality; normalization or improvement of seminal quality has been reported after discontinuation of finasteride [see adverse reactions (6.2) ]. finasteride tablets are not indicated for use in pediatric patients. safety and effectiveness in pediatric patients have not been established. of the total number of subjects included in the long-term efficacy and safety study, 1480 and 105 subjects were 65 and over and 75 and over, respectively. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. no dosage adjustment is necessary in the elderly [see clinical pharmacology (12.3) and clinical studies (14) ]. caution should be exercised in the administration of finasteride in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see clinical pharmacology (12.3) ]. no dosage adjustment is necessary in patients with renal impairment [see clinical pharmacology (12.3) ].

ארצות הברית - אנגלית - NLM (National Library of Medicine)

aurobindo pharma limited - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride 5 mg - finasteride tablets are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to: - improve symptoms - reduce the risk of acute urinary retention - reduce the risk of the need for surgery including transurethral resection of the prostate (turp) and prostatectomy. finasteride tablets administered in combination with the alpha-blocker doxazosin are indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥4 point increase in american urological association (aua) symptom score). finasteride tablets are not approved for the prevention of prostate cancer. finasteride tablets are contraindicated in the following: - hypersensitivity to any component of this medication. - pregnancy. finasteride use is contraindicated in females when they are or may potentially be pregnant. because of the ability of type ii 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (dht), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant female who receives finasteride. if this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant female should be apprised of the potential hazard to the male fetus. [see also warnings and precautions (5.3), use in specific populations (8.1), and how supplied/storage and handling (16).] in female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. risk summary finasteride is contraindicated in pregnant females and not indicated for use in females. based on animal studies and the mechanism of action, finasteride may cause abnormal development of external genitalia in a male fetus if administered to a pregnant female [see warnings and precautions (5.3) and clinical pharmacology (12.1)]. in an embryo-fetal development study in rats, there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring of pregnant rats administered oral finasteride during the period of major organogenesis at doses approximately 0.1 to 86 times the maximum recommended human dose (mrhd) of 5 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day). decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development were also observed in male offspring at oral maternal doses approximately 0.03 times the mrhd (based on auc at animal dose of 0.03 mg/kg/day), along with decreased anogenital distance in male offspring at oral maternal doses approximately 0.003 times the mrhd (based on auc at animal dose of 0.003 mg/kg/day). finasteride is a type ii 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (dht), a hormone necessary for normal development of male genitalia. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus. abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (dht) is inhibited by 5α-reductase inhibitors. these outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. females could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride. with regard to finasteride exposure through the skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. females who are pregnant or may potentially be pregnant should not handle crushed or broken finasteride tablets because of possible exposure of a male fetus. with regard to potential finasteride exposure through semen, three studies have been conducted that measured finasteride concentrations in semen in men receiving finasteride 5 mg/day. in these studies the highest amount of finasteride in semen was estimated to be 50- to 100-fold less than the dose of finasteride (5 mcg) that had no effect on circulating dht levels in men [see data and clinical pharmacology (12.3)]. data human data in 2 studies of healthy subjects (n=69) receiving finasteride 5 mg/day for 6 to 24 weeks, finasteride concentrations in semen ranged from undetectable (<0.1 ng/ml) to 10.54 ng/ml. in an earlier study using a less sensitive assay, finasteride concentrations in semen of 16 subjects receiving finasteride 5 mg/day ranged from undetectable (<1.0 ng/ml) to 21 ng/ml. using the highest semen level measured and assuming 100% absorption would be up to 105 ng per day, which is 50- to 100-fold less than the dose of finasteride (5 mcg) that had no effect on circulating dht levels in men [see clinical pharmacology (12.3)] . animal data in an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). at maternal doses of oral finasteride approximately 0.1 to 86 times the maximum recommended human dose (mrhd) of 5 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. exposure multiples were estimated using data from nonpregnant rats. days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. at oral maternal doses approximately 0.03 times the mrhd (based on auc at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.003 times the mrhd (based on auc at animal dose of 0.003 mg/kg/day). no abnormalities were observed in female offspring at any maternal dose of finasteride. no developmental abnormalities were observed in the offspring of untreated females mated with finasteride treated male rats that received approximately 61 times the mrhd (based on auc at animal dose of 80 mg/kg/day). slightly decreased fertility was observed in male offspring after administration of about 3 times the mrhd (based on auc at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. no effects on fertility were seen in female offspring under these conditions. no evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal oral doses up to 100 mg/kg/day, (finasteride exposure levels were not measured in rabbits). however, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. the fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/ml or about 143 times the highest estimated exposure of pregnant females to finasteride from semen of men taking 5 mg/day) resulted in no abnormalities in male fetuses. in confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of finasteride from semen of men taking 5 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. no other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. risk summary finasteride is not indicated for use in females. infertility females finasteride is not indicated for use in females. males treatment with finasteride for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or ph. a 0.6 ml (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed. these parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks [see warnings and precautions (5.5)]. there have been postmarketing reports of male infertility and/or poor seminal quality; normalization or improvement of seminal quality has been reported after discontinuation of finasteride [see adverse reactions (6.2)]. finasteride is not indicated for use in pediatric patients. safety and effectiveness in pediatric patients have not been established. of the total number of subjects included in a long-term efficacy and safety study, 1480 and 105 subjects were 65 and over and 75 and over, respectively. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. no dosage adjustment is necessary in the elderly [see clinical pharmacology (12.3) and clinical studies (14)] . caution should be exercised in the administration of finasteride in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see clinical pharmacology (12.3)]. no dosage adjustment is necessary in patients with renal impairment [see clinical pharmacology (12.3)] .

ארצות הברית - אנגלית - NLM (National Library of Medicine)

preferred pharmaceuticals inc. - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride 1 mg - finasteride tablets are indicated for the treatment of male pattern hair loss (androgenetic alopecia) in men only . efficacy in bitemporal recession has not been established. finasteride tablets are not indicated for use in women. finasteride tablets are contraindicated in the following: pregnancy category x [see contraindications (4)] . finasteride is contraindicated for use in women who are or may become pregnant. finasteride is a type ii 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (dht), a hormone necessary for normal development of male genitalia. in animal studies, finasteride caused abnormal development of external genitalia in male fetuses. if this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus. abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (dht) is inhibited by 5α-reductase inhibitors. these outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. women could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride. with regard to finasteride exposure through the skin, finasteride tablets are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets because of possible exposure of a male fetus. if a pregnant woman comes in contact with crushed or broken finasteride tablets, the contact area should be washed immediately with soap and water. with regard to potential finasteride exposure through semen, a study has been conducted in men receiving finasteride 1 mg/day that measured finasteride concentrations in semen [see clinical pharmacology (12.3)] . in an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). at maternal doses of oral finasteride approximately 1 to 684 times the recommended human dose (rhd) of 1 mg/day (based on auc at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. exposure multiples were estimated using data from nonpregnant rats. days 16 to 17 of gestation is a critical period in male fetal rats for differentiation of the external genitalia. at oral maternal doses approximately 0.2 times the rhd (based on auc at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the rhd (based on auc at animal dose of 0.003 mg/kg/day). no abnormalities were observed in female offspring exposed to any dose of finasteride in utero . no developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the rhd (based on auc at animal dose of 80 mg/kg/day). slightly decreased fertility was observed in male offspring after administration of about 20 times the rhd (based on auc at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. no effects on fertility were seen in female offspring under these conditions. no evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits). however, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. the fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/ml or about 930 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses. in confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. no other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose. finasteride is not indicated for use in women. it is not known whether finasteride is excreted in human milk. finasteride is not indicated for use in pediatric patients. safety and effectiveness in pediatric patients have not been established. clinical efficacy studies with finasteride did not include subjects aged 65 and over. based on the pharmacokinetics of finasteride 5 mg, no dosage adjustment is necessary in the elderly for finasteride [see clinical pharmacology (12.3)] . however the efficacy of finasteride in the elderly has not been established. caution should be exercised in the administration of finasteride in those patients with liver function abnormalities, as finasteride is metabolized extensively in the liver [see clinical pharmacology (12.3)] . no dosage adjustment is necessary in patients with renal impairment [see clinical pharmacology (12.3)] .

ארצות הברית - אנגלית - NLM (National Library of Medicine)

accord healthcare inc. - bicalutamide (unii: a0z3nau9dp) (bicalutamide - unii:a0z3nau9dp) - bicalutamide 50 mg - bicalutamide tablets 50 mg daily is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (lhrh) analog for the treatment of stage d 2 metastatic carcinoma of the prostate. bicalutamide tablets 150 mg daily is not approved for use alone or with other treatments [see clinical studies (14.2)]. bicalutamide is contraindicated in: - hypersensitivity bicalutamide is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet’s components. hypersensitivity reactions including angioneurotic edema and urticaria have been reported. - women bicalutamide has no indication for women, and should not be used in this population. - pregnancy bicalutamide can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. risk summary bicalutamide is contraindicated for use in pregnant women because it can cause fetal harm. bicalutamide is not indicated for use in females. there are no human data on the use of bicalutamide in pregnant women. in animal reproduction studies, oral administration of bicalutamide to pregnant rats during organogenesis caused abnormal development of reproductive organs in male fetuses at exposures approximately 0.7 to 2 times the human exposure at the recommended dose (see data) . data animal data in an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6 to15, male fetuses had reduced anogenital distance at doses of 10 mg/kg/day and above (approximately 0.7 to 2 times the human exposure at the recommended dose). in a pre- and post-natal development study, female rats were dosed from gestation day 7 to 16 and allowed to litter and rear their offspring to weaning. male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance. in a peri- and post-natal development study, female rats were dosed from gestation day 16 to lactation day 22 and allowed to litter and rear their offspring to weaning. survival and weights of offspring during lactation were reduced for litters from maternal rats receiving doses of 250 mg/kg/day (approximately 2 times the human exposure at the recommended dose). male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance, smaller secondary sex organs, cryptorchidism and hypospadias resulting in an inability to mate and impregnate their female partners. female offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above had reduced pregnancy rates. risk summary bicalutamide is not indicated for use in pregnant women. there is no information available on the presence of bicalutamide in human milk, or on the effects on the breastfed infant or on milk production. bicalutamide has been detected in rat milk. contraception males antiandrogen therapy may cause morphological changes in spermatozoa [see nonclinical toxicology (13.1)]. based on findings in animal reproduction studies and its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 130 days after the final dose of bicalutamide [see use in specific populations (8.1)and clinical pharmacology (12.1)]. infertility males based on animal studies, bicalutamide can lead to inhibition of spermatogenesis and may impair fertility in males of reproductive potential. the long-term effects of bicalutamide tablets on male fertility have not been studied. [see nonclinical toxicology (13.1)] . the safety and effectiveness of bicalutamide in pediatric patients have not been established. bicalutamide orodispersible tablet was studied in combination with anastrozole orodispersible tablet in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty, also known as testotoxicosis. patients were enrolled in the study if they had a baseline age ≥ 2 years and a diagnosis of testotoxicosis based on clinical features of progressive precocious puberty, symmetrical testicular enlargement, advanced bone age, pubertal levels of serum testosterone, prepubertal pattern of gonadotropin secretion following a gnrh stimulation test, and absence of other clinical and biochemical causes of testosterone excess. thirteen out of the 14 patients enrolled completed 12 months of combination treatment (one patient was lost to follow-up). if central precocious puberty (cpp) developed, an lhrh analog was to be added. four patients were diagnosed with cpp during the 12-month study and received lhrh analog treatment and 2 additional patients were diagnosed at the end of the 12 months and received treatment subsequently. mean ± sd characteristics at baseline were as follows: chronological age: 3.9±1.9 years; bone age 8.8±2.5; bone age/chronological age ratio: 2.06 ± 0.51; growth rate (cm/yr): 10.81 ± 4.22; growth rate standard deviation score (sds): 0.41 ± 1.36. the starting bicalutamide dose was 12.5 mg. bicalutamide was titrated in each patient until steady-state r-bicalutamide (the active isomer of bicalutamide) trough plasma concentration reached 5 to 15 mcg/ml, which is the range of therapeutic concentrations achieved in adults with prostate cancer following the administration of the currently approved bicalutamide dose of 50 mg. the starting daily dose of anastrozole was 0.5 mg. anastrozole was independently titrated in each patient until it reached at steady-state a serum estradiol concentration of <10 pmol/l (2.7 pg/ml). the following ascending doses were used for bicalutamide: 12.5 mg, 25 mg, 50 mg, and 100 mg. for anastrozole there were two ascending doses: 0.5 mg and 1 mg. at the end of the titration phase, 1 patient was on 12.5 mg bicalutamide, 8 patients were on 50 mg bicalutamide, and 4 patients were on 100 mg bicalutamide; 10 patients were on 0.5 mg anastrozole and 3 patients were on 1 mg anastrozole. in the majority of patients, steady-state trough concentrations of r-bicalutamide appeared to be attained by day 21 with once daily dosing. steady-state trough plasma anastrozole concentrations appeared to be attained by day 8. the primary efficacy analysis of the study was to assess the change in growth rate after 12 months of treatment, relative to the growth rate during the ≥6 months prior to entering the study. pre-study growth rates were obtained retrospectively. there was no statistical evidence that the growth rate was reduced during treatment. during bicalutamide /anastrozole treatment the mean growth rate (cm/yr) decreased by 1.6 cm/year, 95% ci (-4.7 to 1.5) p=0.28; the mean growth rate sds decreased by 0.1 sd, 95% ci (–1.2 to 1.0) p=0.88. table 2 shows descriptive data for growth rates for the overall population and for subgroups defined by history of previous treatment for testotoxicosis with ketoconazole, spironolactone, anastrozole or other aromatase inhibitors. endpoint analysis population pre-study mean change from pre-study to 12 months mean median (min, max) growth rate (cm/yr) all treated (n=13) 10.8 -1.6 -2.8 (-7.4, 8.4) 9/13 (69%) pt †(n=6) 10.3 -0.2 -2.6 ‡ (-7.2, 8.4) 4/6 (67%) npt §(n=7) 11.2 -2.8 -2.8 (-7.4, 1.1) 5/7 (71%) growth rate (sd units) all treated (n=13) 0.4 -0.1 -0.4 (-2.7, 3.5) 9/13 (69%) pt †(n=6) -0.1 +0.7 -0.2 ‡ (-1.6, 3.5) 4/6 (67%) npt §(n=7) 0.8 -0.7 -0.4 (-2.7, 0.5) 5/7 (71%) total testosterone concentrations increased by a mean of 5 mmol/l over the 12 months of treatment from a baseline mean of 10 mmol/l. estradiol concentrations were at or below the level of quantification (9.81 pmol/l) for 11 of 12 patients after 12 months of treatment. six of the 12 patients started treatment at an estradiol concentration below the level of quantification. there were no deaths, serious adverse events, or discontinuations due to adverse events during the study. of the 14 patients exposed to study treatment, 13 (92.9%) experienced at least one adverse event. the most frequently reported (>3 patients) adverse events were gynecomastia (7/14, 50%), central precocious puberty (6/14, 43%), vomiting (5/14, 36%), headache (3/14, 21%), pyrexia (3/14, 21%), and upper respiratory tract infection (3/14, 21%). adverse reactions considered possibly related to bicalutamide by investigators included gynecomastia (6/14, 43%), central precocious puberty (2/14, 14%), breast tenderness (2/14, 14%), breast pain (1/14, 7%), asthenia (1/14, 7%), increased alanine aminotransferase [alt] (1/14, 7%), increased aspartate aminotransferase [ast] (1/14, 7%), and musculoskeletal chest pain (1/14, 7%). headache was the only adverse reaction considered possibly related to anastrozole by investigators. for the patient who developed elevated alt and ast, the elevation was <3x uln, and returned to normal without stopping treatment; there was no concomitant elevation in total bilirubin. in two studies in patients given 50 or 150 mg daily, no significant relationship between age and steady-state levels of total bicalutamide or the active r-enantiomer has been shown. bicalutamide should be used with caution in patients with moderate-to-severe hepatic impairment. bicalutamide is extensively metabolized by the liver. limited data in subjects with severe hepatic impairment suggest that excretion of bicalutamide may be delayed and could lead to further accumulation. periodic liver function tests should be considered for hepatic-impaired patients on long-term therapy [see warnings and precautions (5.1)]. no clinically significant difference in the pharmacokinetics of either enantiomer of bicalutamide was noted in patients with mild-to-moderate hepatic disease as compared to healthy controls. however, the half-life of the r-enantiomer was increased approximately 76% (5.9 and 10.4 days for normal and impaired patients, respectively) in patients with severe liver disease (n=4). renal impairment (as measured by creatinine clearance) had no significant effect on the elimination of total bicalutamide or the active r-enantiomer.

ארצות הברית - אנגלית - NLM (National Library of Medicine)

golden state medical supply, inc. - bicalutamide (unii: a0z3nau9dp) (bicalutamide - unii:a0z3nau9dp) - bicalutamide 50 mg - bicalutamide tablets 50 mg daily is indicated for use in combination therapy with a luteinizing hormone-releasing hormone (lhrh) analog for the treatment of stage d 2 metastatic carcinoma of the prostate. bicalutamide tablets 150 mg daily is not approved for use alone or with other treatments [see clinical studies (14.2)]. bicalutamide is contraindicated in: - hypersensitivity bicalutamide is contraindicated in any patient who has shown a hypersensitivity reaction to the drug or any of the tablet’s components. hypersensitivity reactions including angioneurotic edema and urticaria have been reported. - women bicalutamide has no indication for women, and should not be used in this population. - pregnancy bicalutamide can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)]. risk summary bicalutamide is contraindicated for use in pregnant women because it can cause fetal harm. bicalutamide is not indicated for use in females. there are no human data on the use of bicalutamide in pregnant women. in animal reproduction studies, oral administration of bicalutamide to pregnant rats during organogenesis caused abnormal development of reproductive organs in male fetuses at exposures approximately 0.7 to 2 times the human exposure at the recommended dose (see data) . data animal data in an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6 to15, male fetuses had reduced anogenital distance at doses of 10 mg/kg/day and above (approximately 0.7 to 2 times the human exposure at the recommended dose). in a pre- and post-natal development study, female rats were dosed from gestation day 7 to 16 and allowed to litter and rear their offspring to weaning. male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance. in a peri- and post-natal development study, female rats were dosed from gestation day 16 to lactation day 22 and allowed to litter and rear their offspring to weaning. survival and weights of offspring during lactation were reduced for litters from maternal rats receiving doses of 250 mg/kg/day (approximately 2 times the human exposure at the recommended dose). male offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above, were observed to have reduced anogenital distance, smaller secondary sex organs, cryptorchidism and hypospadias resulting in an inability to mate and impregnate their female partners. female offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above had reduced pregnancy rates. risk summary bicalutamide is not indicated for use in pregnant women. there is no information available on the presence of bicalutamide in human milk, or on the effects on the breastfed infant or on milk production. bicalutamide has been detected in rat milk. contraception males antiandrogen therapy may cause morphological changes in spermatozoa [see nonclinical toxicology (13.1)]. based on findings in animal reproduction studies and its mechanism of action, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 130 days after the final dose of bicalutamide [see use in specific populations (8.1)and clinical pharmacology (12.1)]. infertility males based on animal studies, bicalutamide can lead to inhibition of spermatogenesis and may impair fertility in males of reproductive potential. the long-term effects of bicalutamide tablets on male fertility have not been studied. [see nonclinical toxicology (13.1)] . the safety and effectiveness of bicalutamide in pediatric patients have not been established. bicalutamide orodispersible tablet was studied in combination with anastrozole orodispersible tablet in an open-label, non-comparative, multi-center study that assessed the efficacy and safety of this combination regimen over 12 months in the treatment of gonadotropin-independent precocious puberty in boys with familial male-limited precocious puberty, also known as testotoxicosis. patients were enrolled in the study if they had a baseline age ≥ 2 years and a diagnosis of testotoxicosis based on clinical features of progressive precocious puberty, symmetrical testicular enlargement, advanced bone age, pubertal levels of serum testosterone, prepubertal pattern of gonadotropin secretion following a gnrh stimulation test, and absence of other clinical and biochemical causes of testosterone excess. thirteen out of the 14 patients enrolled completed 12 months of combination treatment (one patient was lost to follow-up). if central precocious puberty (cpp) developed, an lhrh analog was to be added. four patients were diagnosed with cpp during the 12-month study and received lhrh analog treatment and 2 additional patients were diagnosed at the end of the 12 months and received treatment subsequently. mean ± sd characteristics at baseline were as follows: chronological age: 3.9±1.9 years; bone age 8.8±2.5; bone age/chronological age ratio: 2.06 ± 0.51; growth rate (cm/yr): 10.81 ± 4.22; growth rate standard deviation score (sds): 0.41 ± 1.36. the starting bicalutamide dose was 12.5 mg. bicalutamide was titrated in each patient until steady-state r-bicalutamide (the active isomer of bicalutamide) trough plasma concentration reached 5 to 15 mcg/ml, which is the range of therapeutic concentrations achieved in adults with prostate cancer following the administration of the currently approved bicalutamide dose of 50 mg. the starting daily dose of anastrozole was 0.5 mg. anastrozole was independently titrated in each patient until it reached at steady-state a serum estradiol concentration of <10 pmol/l (2.7 pg/ml). the following ascending doses were used for bicalutamide: 12.5 mg, 25 mg, 50 mg, and 100 mg. for anastrozole there were two ascending doses: 0.5 mg and 1 mg. at the end of the titration phase, 1 patient was on 12.5 mg bicalutamide, 8 patients were on 50 mg bicalutamide, and 4 patients were on 100 mg bicalutamide; 10 patients were on 0.5 mg anastrozole and 3 patients were on 1 mg anastrozole. in the majority of patients, steady-state trough concentrations of r-bicalutamide appeared to be attained by day 21 with once daily dosing. steady-state trough plasma anastrozole concentrations appeared to be attained by day 8. the primary efficacy analysis of the study was to assess the change in growth rate after 12 months of treatment, relative to the growth rate during the ≥6 months prior to entering the study. pre-study growth rates were obtained retrospectively. there was no statistical evidence that the growth rate was reduced during treatment. during bicalutamide /anastrozole treatment the mean growth rate (cm/yr) decreased by 1.6 cm/year, 95% ci (-4.7 to 1.5) p=0.28; the mean growth rate sds decreased by 0.1 sd, 95% ci (–1.2 to 1.0) p=0.88. table 2 shows descriptive data for growth rates for the overall population and for subgroups defined by history of previous treatment for testotoxicosis with ketoconazole, spironolactone, anastrozole or other aromatase inhibitors. endpoint analysis population pre-study mean change from pre-study to 12 months mean median (min, max) growth rate (cm/yr) all treated (n=13) 10.8 -1.6 -2.8 (-7.4, 8.4) 9/13 (69%) pt †(n=6) 10.3 -0.2 -2.6 ‡ (-7.2, 8.4) 4/6 (67%) npt §(n=7) 11.2 -2.8 -2.8 (-7.4, 1.1) 5/7 (71%) growth rate (sd units) all treated (n=13) 0.4 -0.1 -0.4 (-2.7, 3.5) 9/13 (69%) pt †(n=6) -0.1 +0.7 -0.2 ‡ (-1.6, 3.5) 4/6 (67%) npt §(n=7) 0.8 -0.7 -0.4 (-2.7, 0.5) 5/7 (71%) total testosterone concentrations increased by a mean of 5 mmol/l over the 12 months of treatment from a baseline mean of 10 mmol/l. estradiol concentrations were at or below the level of quantification (9.81 pmol/l) for 11 of 12 patients after 12 months of treatment. six of the 12 patients started treatment at an estradiol concentration below the level of quantification. there were no deaths, serious adverse events, or discontinuations due to adverse events during the study. of the 14 patients exposed to study treatment, 13 (92.9%) experienced at least one adverse event. the most frequently reported (>3 patients) adverse events were gynecomastia (7/14, 50%), central precocious puberty (6/14, 43%), vomiting (5/14, 36%), headache (3/14, 21%), pyrexia (3/14, 21%), and upper respiratory tract infection (3/14, 21%). adverse reactions considered possibly related to bicalutamide by investigators included gynecomastia (6/14, 43%), central precocious puberty (2/14, 14%), breast tenderness (2/14, 14%), breast pain (1/14, 7%), asthenia (1/14, 7%), increased alanine aminotransferase [alt] (1/14, 7%), increased aspartate aminotransferase [ast] (1/14, 7%), and musculoskeletal chest pain (1/14, 7%). headache was the only adverse reaction considered possibly related to anastrozole by investigators. for the patient who developed elevated alt and ast, the elevation was <3x uln, and returned to normal without stopping treatment; there was no concomitant elevation in total bilirubin. in two studies in patients given 50 or 150 mg daily, no significant relationship between age and steady-state levels of total bicalutamide or the active r-enantiomer has been shown. bicalutamide should be used with caution in patients with moderate-to-severe hepatic impairment. bicalutamide is extensively metabolized by the liver. limited data in subjects with severe hepatic impairment suggest that excretion of bicalutamide may be delayed and could lead to further accumulation. periodic liver function tests should be considered for hepatic-impaired patients on long-term therapy [see warnings and precautions (5.1)]. no clinically significant difference in the pharmacokinetics of either enantiomer of bicalutamide was noted in patients with mild-to-moderate hepatic disease as compared to healthy controls. however, the half-life of the r-enantiomer was increased approximately 76% (5.9 and 10.4 days for normal and impaired patients, respectively) in patients with severe liver disease (n=4). renal impairment (as measured by creatinine clearance) had no significant effect on the elimination of total bicalutamide or the active r-enantiomer.

ארמניה - אנגלית - Դեղերի և բժշկական տեխնոլոգիաների փորձագիտական կենտրոնի գործունեության Հայաստանի Հանրապետությունում

specgx llc - methadone (methadone hydrochloride) - tablets - 5mg

ארמניה - אנגלית - Դեղերի և բժշկական տեխնոլոգիաների փորձագիտական կենտրոնի գործունեության Հայաստանի Հանրապետությունում

specgx llc - methadone (methadone hydrochloride) - tablets - 10mg