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medicines development for global health - moxidectin (unii: ngu5h31yo9) (moxidectin - unii:ngu5h31yo9) - moxidectin tablets are indicated for the treatment of onchocerciasis due to onchocerca volvulus  in patients aged 12 years and older [ see clinical studies ( 14 ) ] . limitations of use: moxidectin tablets do not kill adult o .  volvulus . follow-up evaluation is advised. the safety and efficacy of repeat administration of moxidectin tablets in patients with o .  volvulus has not been studied. none. risk summary available data from clinical trials on the use of moxidectin tablets in pregnant women are insufficient to establish whether there is a moxidectin-associated risk for major birth defects and miscarriage . moxidectin administered orally to pregnant rats during the period of organogenesis was not associated with significant embryo-fetal developmental effects at doses of approximately 15 times the recommended human dose based on body surface area (bsa) comparison. when moxidectin was dosed orally to pregnant rabbits during the period of organogenesis, no embryo-fetal developmental effects were observed at oral doses of moxidectin up to 24 times the recommended human dose based on bsa comparison ( see data ) . daily administration of moxidectin by oral gavage to maternal female rats during organogenesis and through lactation was associated with decreased survival, adverse clinical signs, and decreased body weights in first-generation offspring during the lactation period at a moxidectin dose less than 2-times the recommended human dose based on bsa comparison. additional findings in first-generation offspring at the same dose included delays in pinna unfolding, eye opening, and vaginal opening. other parameters, including reproduction and neurological development in first-generation offspring were not affected at any moxidectin dose ( see data ) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss or other adverse outcomes. 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 a rat embryo-fetal development study, daily oral administration of moxidectin at 12 mg/kg/day (approximately 15 times the recommended human dose of 8 mg based on bsa comparison) during gestation days (gds) 6 to 15 significantly increased the fetal incidence, but not the litter incidence of cleft palate and the fetal and litter incidence of a skeletal variation, wavy ribs, at a maternally toxic dose. mean maternal food consumption, body weights, and body weight gain were significantly decreased at moxidectin doses of 10 and 12 mg/kg/day compared to control values. the no observed adverse effect level (noael) value for maternal and fetal toxicity was considered to be 5 and 10 mg/kg/day respectively (approximately 6 and 12 times, respectively, the recommended human dose based on bsa comparison). in the rabbit, daily oral administration of moxidectin at ≥ 5 mg/kg/day from gd 7 to gd 19 was not associated with fetal weight loss or malformations but resulted in significantly decreased maternal food consumption and body weight gains. the noael values for maternal and fetal toxicity in the rabbit was 1 mg/kg/day and 10 mg/kg/day respectively (approximately 2 times and 24 times, respectively, the recommended human dose based on bsa comparison). in a pre-postnatal study, moxidectin doses of 0.2 and 0.5 mg/kg/day were administered by oral gavage to maternal female rats from gd 6 throughout the lactation period until ld 21. a third dose group that received maternal doses of 1.5 mg/kg/day moxidectin (less than 2-times the recommended human dose based on bsa comparison) was divided into two cohorts with cohort 1 receiving maternal doses from gd 6 until ld 10 and cohort 2 receiving maternal doses from gd 6 until each individual animal littered, but not during the lactation period. first-generation offspring in cohort 1 had adverse clinical signs (small body size, thin, weak, subdued/sluggish, pale, cold to touch, respiratory distress, blue coloration and/or no visible milk in stomach) and decreased survival and body weights during the lactation period. however, first-generation offspring in cohort 2 did not experience adverse clinical signs, body weight loss, or reduced survival suggesting moxidectin in lactation milk was responsible for the adverse effects in offspring in cohort 1. additional findings included delays in pinna unfolding and eye opening in male and female offspring in both cohorts and delay of vaginal opening in female offspring in cohort 2. no adverse effects were noted in offspring at a maternal dose of 0.5 mg/kg/day (approximately 0.6 times the recommended human dose based on bsa comparison). reproductive performance based on mating and fertility indices and neurological development were not affected in male and female first-generation offspring at any of the administered moxidectin doses. in another pre-postnatal study in rats, parental oral administration of dietary moxidectin prior to mating, through mating, gestation, and lactation did not produce adverse effects in first-generation or second-generation offspring at a maternal noael dose of 0.824 mg/kg/day (approximately equivalent to the recommended human dose based on bsa comparison). however, at moxidectin doses ≥ 1.1 mg/kg/day (approximately equivalent to 1.3 times the recommended human dose based on bsa comparison), the survival and body weights of first-generation offspring were significantly decreased during the lactation period, and the number of live fetuses at birth was significantly decreased with a maternal moxidectin dose of 11 mg/kg/day (approximately equivalent to 13 times the recommended human dose based on bsa comparison). in this study, offspring were assessed for survival, body weights, and fertility, and developmental milestones were not assessed. risk summary moxidectin was detected in the milk of lactating women following a single 8 mg dose of moxidectin tablets ( see  data ) . there are no data on the effects of moxidectin tablets on the breast-fed infant or milk production. in a pre-postnatal study in rats, oral gavage administration of moxidectin at a dose less than 2-times the recommended human dose based on bsa comparison during the lactation period resulted in adverse clinical signs, weight loss, and increased mortality in rat pups suggesting moxidectin in lactation milk was responsible for the adverse effects [ see use in specific populations ( 8.1 ), and data ] . because of serious findings from the rat pre-postnatal study including weight loss and death, advise women that breastfeeding is not recommended at the time of treatment with moxidectin tablets and for 7 days after treatment. data a pharmacokinetic study in twelve healthy adult lactating women who were 21 to 100 weeks post partum evaluated the concentrations of moxidectin in plasma and breast milk collected over a period of 28 days following a single 8 mg dose of moxidectin tablets. the mean (± sd) exposure ratio of moxidectin present in human breast milk to that of human plasma was approximately 1.77 (± 0.66) over a collection period of 28 days. the estimated mean (± sd) total infant dose, assuming the infants would consume all the breast milk collected during the study, was 0.056 mg (± 0.024 mg), which would be approximately 0.70% (± 0.30%) of the maternal dose. relative infant dose was estimated to be 8.73% (± 0.024 mg). the effects of moxidectin or its metabolites on the breast-fed child or milk production were not evaluated. the safety and effectiveness of moxidectin tablets have been established in pediatric patients 12 years of age and older. in trial 1, (n = 53 patients aged 12 to 17 years), the safety and effectiveness was similar to that observed in adults [see adverse reactions ( 6.1 ), and clinical studies ( 14 )] . the safety and effectiveness of moxidectin tablets in pediatric patients under 12 years of age has not been established. of the total number of patients included in trial 1 that were treated with moxidectin tablets, 83 were aged 65 and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out  [see clinical studies ( 14 ) and clinical pharmacology ( 12.3 )] . no dose adjustment of moxidectin tablets is necessary for patients with mild (creatinine clearance (crcl) 60 to 89 ml/min) to moderate (crcl 30 to 59 ml/min) renal impairment. the safety of moxidectin tablets in patients with severe renal impairment (crcl 15 to 29 ml/min) or end stage renal disease, is unknown [ see clinical pharmacology ( 12.3 ) ].

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ani pharmaceuticals, inc. - bicalutamide (unii: a0z3nau9dp) (bicalutamide - unii:a0z3nau9dp) - 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 d2 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 tablets are contraindicated in: bicalutamide tablets are 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. bicalutamide tablets have no indication for women, and should not be used in this population. bicalutamide tablets can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . risk summary bicalutamide tablets are contraindicated for use in pregnant women because it can cause fetal harm. bicalutamide tablets are not indicated for use in females. there are no human data on the use of bicalutamide tablets 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 6-15, 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 7-16 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 tablets are 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 tablets [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 on male fertility have not been studied [see nonclinical toxicology (13.1)] . the safety and effectiveness of bicalutamide tablets 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 5-15 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. table 2. growth rates analysis population pre-study mean change from pre-study to 12 months % patients with growth reduction1 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%) pt2 (n=6) 10.3 -0.2 -2.63 (-7.2, 8.4) 4/6 (67%) npt4 (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%) pt2 (n=6) -0.1 +0.7 -0.23 (-1.6, 3.5) 4/6 (67%) npt4 (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 tablets 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.

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organon llc - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - proscar® is indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to: proscar administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥4 point increase in american urological association (aua) symptom score). proscar is not approved for the prevention of prostate cancer. proscar is 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 proscar is contraindicated in pregnant females and not indicated for use in females. based on animal studies and the mechanism of action, proscar 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). proscar 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 proscar tablets or semen from a male partner taking proscar. with regard to finasteride exposure through the skin, proscar 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 proscar 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 proscar 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 μg) 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 proscar 5 mg/day for 6-24 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 proscar 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 μg) 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 6-18) 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 20-100), 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 proscar is not indicated for use in females. infertility females proscar is not indicated for use in females. males treatment with proscar 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)]. proscar 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 pless, 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 proscar 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)] .

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remedyrepack inc. - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - finasteride tablets usp, are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to:  -improve symptoms -reduce the risk of the need for surgery including transurethral resection of the prostate (turp) and prostatectomy. finasteride tablets usp administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of bph (a confirmed ≥4 point increase in american urological association (aua) symptom score). finasteride tablets usp are not approved for the prevention of prostate cancer. finasteride tablets usp are contraindicated in the following: • hypersensitivity to any component of this medication. •  pregnancy . finasteride use is contraindicated in women 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 woman who receives finasteride. if this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. [see also warnings and precautions (5.3) , use in specific populations (8.1) , how supplied/storage and handling (16) and patient counseling information (17.2) .] in female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. teratogenic effects: pregnancy category x. [see contraindications (4).] finasteride tablets usp are contraindicated for use in women who are or may become pregnant. finasteride tablets usp 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 usp or semen from a male partner taking finasteride tablets usp. with regard to finasteride exposure through the skin, finasteride tablets usp 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 usp because of possible exposure of a male fetus. if a pregnant woman comes in contact with crushed or broken finasteride tablets usp, the contact area should be washed immediately with soap and water. with regard to potential finasteride exposure through semen, two studies have been conducted in men receiving finasteride tablets usp, 5 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 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 days 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 women 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. finasteride tablets usp is not indicated for use in women. it is not known whether finasteride is excreted in human milk. finasteride tablets usp 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 tablets usp 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)].

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

quallent pharmaceuticals health llc - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - 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)] .

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

remedyrepack inc. - finasteride (unii: 57gno57u7g) (finasteride - unii:57gno57u7g) - 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)] .

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

bryant ranch prepack - dutasteride (unii: o0j6xjn02i) (dutasteride - unii:o0j6xjn02i) - dutasteride capsules 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 (aur), and - reduce the risk of the need for bph-related surgery. dutasteride in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic bph in men with an enlarged prostate. dutasteride is not approved for the prevention of prostate cancer. dutasteride is contraindicated for use in: - pregnancy. dutasteride use is contraindicated in women who are pregnant. in animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. therefore, dutasteride may cause fetal harm when administered to a pregnant woman [see warnings and precautions (5.4), use in specific populations (8.1)] . - patients with previously demonstrated clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors [see adverse reactions (6.2)] . risk summary dutasteride is contraindicated for use in pregnancy because it may cause harm to the male fetus [see contraindications (4)] . dutasteride is not indicated for use in women. dutasteride is a 5 alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (dht), a hormone necessary for normal development of male genitalia. abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of this conversion. these results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. 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. in animal reproduction studies, dutasteride inhibited normal development of external genitalia in male offspring when given to rats or rabbits during organogenesis at less than the maximum recommended human dose (mrhd) of 0.5 mg daily, in the absence of maternal toxicity. at 15 times the mrhd, prolonged pregnancy, decreased reproductive organ weights, and delayed puberty in male offspring were observed in rats, with no-effect levels less than the mrhd of 0.5 mg daily. increased placental weights in rabbits were also observed, with no-effect levels less than the mrhd of 0.5 mg daily (see data) . although dutasteride is secreted into human semen, the drug concentration in the human female partner is approximately 100 times less than concentrations producing abnormalities of male genitalia in animal studies (see data) . in monkeys dosed during organogenesis at blood concentrations comparable to or above levels to which a human female partner is estimated to be exposed, male offspring external genitalia was not adversely affected. no feminization occurred in male offspring of untreated female rats mated to treated male rats even though detectable blood levels of dutasteride were observed in the female rats [see nonclinical toxicology (13.1)] . data human data: the highest measured semen concentration of dutasteride in treated men was 14 ng/ml. although dutasteride is detected in semen, assuming exposure of a 50-kg woman to 5 ml of semen and 100% absorption, the woman’s expected dutasteride blood concentration through semen would be about 0.0175 ng/ml. this concentration is approximately 100 times less than blood concentrations producing abnormalities of male genitalia in animal studies. dutasteride is highly protein bound in human semen (greater than 96%), which may reduce the amount of dutasteride available for vaginal absorption. animal data: in an embryo-fetal development study in rats, oral administration of dutasteride at 10 times less than the mrhd of 0.5 mg daily (based on average blood levels in men) resulted in feminization of male genitalia in the fetus (decreased anogenital distance at 0.05 mg/kg/day, with a lack of a no-effect level) in the absence of maternal toxicity. in addition, nipple development, hypospadias, and distended preputial glands occurred in fetuses of dams treated at doses of 2.5 mg/kg/day or greater (approximately 15 times the mrhd). reduced fetal body weight and associated delayed ossification in the presence of maternal toxicity (decreased body weight gain) were observed at maternal exposure approximately 15 times the mrhd (dose of 2.5 mg/kg/day or greater). an increase in stillborn pups was observed in dams treated at 30 mg/kg/day (approximately 111 times the mrhd), with a no-effect level of 12.5 mg/kg/day. in a rabbit embryo-fetal development study, doses 28 times the mrhd (doses of 30 mg/kg/day or greater), based on average blood levels in men, were administered orally on gestation days 7 to 29 (during organogenesis and the late period of external genitalia development). histological evaluation of the genital papilla of fetuses revealed evidence of feminization of the male fetus as well as fused skull bones and increased placental weights at all doses in the absence of maternal toxicity. a second embryo-fetal development study in rabbits dosed throughout pregnancy (organogenesis and later period of external genitalia development [gestation days 6 to 29]) at 0.3 times the mrhd (doses of 0.05 mg/kg/day or greater, with no no-effect level), also produced evidence of feminization of the genitalia in male fetuses and increased placental weights at all doses in the absence of maternal toxicity. in an embryo-fetal development study, pregnant rhesus monkeys were exposed intravenously during organogenesis (gestation days 20 to 100) to a dutasteride blood level comparable to or above the estimated dutasteride exposure of a human female partner. dutasteride was administered on gestation days 20 to 100 (during organogenesis) at doses of 400, 780, 1,325, or 2,010 ng/day (12 monkeys/group). no feminization of male external genitalia of monkey offspring was observed. reduction of fetal adrenal weights, reduction in fetal prostate weights, and increases in fetal ovarian and testis weights were observed at the highest dose tested. based on the highest measured semen concentration of dutasteride in treated men (14 ng/ml), these doses in the monkey represent up to 16 times the potential maximum exposure of a 50-kg human female to 5 ml of semen daily from a dutasteride-treated male, assuming 100% absorption. the dose levels (on a ng/kg basis) administered to monkeys in this study are 32 to 186 times the nominal (ng/kg) dose to which a female would potentially be exposed via the semen. it is not known whether rabbits or rhesus monkeys produce any of the major human metabolites. in an oral pre- and post-natal development study in rats, feminization of the male genitalia was observed. decreased anogenital distance was observed at 0.05 times the mrhd and greater  (0.05 mg/kg/day and greater), with a lack of a no-effect level, based on average blood levels in men as an estimation of auc. hypospadias and nipple development were observed at 2.5 mg/kg/day or greater (14 times the mrhd or greater, with a no-effect level at 0.05 mg/kg/day). doses of 2.5 mg/kg/day and greater also resulted in prolonged gestation in the parental females, an increase in time to balano-preputial separation in male offspring, a decrease in time to vaginal patency for female offspring, and a decrease in prostate and seminal vesicle weights in male offspring. increased stillbirths and decreased neonatal viability in offspring were noted at 30 mg/kg/day (102 times the mrhd in the presence of maternal toxicity [decreased body weights]). risk summary dutasteride is not indicated for use in women. there is no information available on the presence of dutasteride in human milk, the effects on the breastfed child, or the effects on milk production.  infertility males: the effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers aged 18 to 52 years (n = 27 dutasteride, n = 23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. at 52 weeks, the mean percent reductions from baseline in total sperm count, semen volume, and sperm motility were 23%, 26%, and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in the placebo group. sperm concentration and sperm morphology were unaffected. after 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. while mean values for all semen parameters at all timepoints remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2 subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52 weeks, with partial recovery at the 24-week follow-up. the clinical significance of dutasteride’s effect on semen characteristics for an individual patient’s fertility is not known [see warnings and precautions (5.6)] . dutasteride is not indicated for use in pediatric patients. safety and effectiveness in pediatric patients have not been established. of 2,167 male subjects treated with dutasteride in 3 clinical trials, 60% were aged 65 years and older and 15% were aged 75 years and older. no overall differences in safety or efficacy were observed between these subjects and younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see clinical pharmacology (12.3)] . no dose adjustment is necessary for dutasteride in patients with renal impairment [see clinical pharmacology (12.3)] . the effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients. however, in a clinical trial where 60 subjects received 5 mg (10 times the therapeutic dose) daily for 24 weeks, no additional adverse events were observed compared with those observed at the therapeutic dose of 0.5 mg [see clinical pharmacology (12.3)] .

Singapore - English - HSA (Health Sciences Authority)

galderma singapore private limited - clobetasol propionate - shampoo - 0.05% - clobetasol propionate 0.05%

Singapore - English - HSA (Health Sciences Authority)

dksh singapore pte. ltd. - teriparatide (rdna origin) - injection, solution - 750 mcg/3 ml - teriparatide (rdna origin) 750 mcg/3 ml

Singapore - English - HSA (Health Sciences Authority)

novartis (singapore) pte ltd - carbamazepine - tablet - 200 mg - carbamazepine 200 mg