Stati Uniti - Ingliż - NLM (National Library of Medicine)

actavis pharma, inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): - in adults to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . - in pediatric patients aged 3 years and older with idiopathic or congenital pah to improve pulmonary vascular resistance (pvr), which is expected to result in an improvement in exercise ability. use of bosentan is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . coadministration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of bosentan and cyclosporine a is contraindicated [see cytochrome p450  drug interactions (7.1)] . an increased risk of liver enzyme elevations was observed in patients receiving glyburide concomitantly with bosentan. therefore coadministration of glyburide and bosentan is contraindicated [see cytochrome p450  drug interactions (7.1)] . bosentan is contraindicated in patients who are hypersensitive to bosentan or any component of the product. observed reactions include drug reaction with eosinophilia and systemic symptoms (dress), anaphylaxis, rash, and angioedema [see adverse reactions (6.2), description (11)] . risk summary based on data from animal reproduction studies, bosentan may cause fetal harm, including birth defects and fetal death, when administered to a pregnant female and is contraindicated during pregnancy [see contraindications (4.1)] . there are limited data on bosentan use in pregnant women. in animal reproduction studies, oral administration of bosentan to pregnant rats at 2-times the maximum recommended human dose (mrhd) on a mg/m2 basis caused teratogenic effects in rats, including malformations of the head, mouth, face, and large blood vessels [see animal data] . advise pregnant women of the potential risk to a fetus. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 bosentan was teratogenic in rats given oral doses two times the mrhd (on a mg/m2 basis). in an embryo-fetal toxicity study in rats, bosentan showed dose-dependent teratogenic effects, including malformations of the head, mouth, face and large blood vessels. bosentan increased stillbirths and pup mortality at oral doses 2 and 10 times the mrhd (on a mg/m2 basis). although birth defects were not observed in rabbits given oral doses of up to the equivalent of 10.5 g/day in a 70 kg person, plasma concentrations of bosentan in rabbits were lower than those reached in the rat. the similarity of malformations induced by bosentan and those observed in endothelin-1 knockout mice and in animals treated with other endothelin receptor antagonists indicates that embryo-fetal toxicity is a class effect of these drugs. risk summary there are no data on the presence of bosentan in human milk, the effects on the breastfed infant, or the effect on milk production. because of the potential for serious adverse reactions, such as fluid retention and hepatotoxicity, in breastfed infants from bosentan, advise women not to breastfeed during treatment with bosentan. pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating bosentan, monthly during treatment and one month after stopping treatment with bosentan. the patient should contact her physician immediately for pregnancy testing if onset of menses is delayed or pregnancy is suspected. if the pregnancy test is positive, the physician and patient must discuss the risks to her, the pregnancy, and the fetus. contraception drug interaction studies show that bosentan reduces serum levels of the estrogen and progestin in oral contraceptives. based on these findings, hormonal contraceptives (including oral, injectable, transdermal, and implantable contraceptives) may be less effective for preventing pregnancy in patients using bosentan and should not be used as a patient’s only contraceptive method [see drug interactions (7.2)] . females of reproductive potential using bosentan must use two acceptable methods of contraception during treatment and for 1 month after treatment with bosentan. patients may choose one highly effective form of contraception (intrauterine devices (iud) or tubal sterilization) or a combination of methods (hormone method with a barrier method or two barrier methods). if a partner’s vasectomy is the chosen method of contraception, a hormone or barrier method must be used along with this method. counsel patients on pregnancy planning and prevention, including emergency contraception, or designate counseling by another healthcare provider trained in contraceptive counseling [see boxed warning] . infertility males decreased sperm counts have been observed in patients receiving bosentan. based on these findings and findings in animals, bosentan may impair fertility in males of reproductive potential. it is not known whether effects on fertility would be reversible [see warnings and precautions (5.6), adverse reactions (6.1), nonclinical toxicology (13.1)] . the efficacy of bosentan in patients <18 years is supported by data from an uncontrolled trial in which 19 pediatric patients were treated with bosentan. in this study, cardiopulmonary hemodynamic improvements were similar to those seen in adults treated with bosentan [see pulmonary arterial hypertension (14.1)] . safety in pediatric patients is supported by data from 100 pediatric patients treated with bosentan for a median of 17 months [see clinical studies experience (6.1), pulmonary arterial hypertension (14.1)] . juvenile animal toxicity data in a juvenile rat toxicity study, rats were treated from day 4 postpartum to adulthood (day 69 postpartum). decreased body weights, absolute weights of testes and epididymides, and reduced number of sperm in epididymides were observed after weaning. no effect on testis histology or sperm morphology and function was seen. the noael was 4 times (at day 4 postpartum) and 2 times (day 69 postpartum) the human therapeutic exposure, respectively. no effects on general development, sensory, cognitive function and reproductive performance were detected at the highest dose tested in juvenile rats, 7 times the therapeutic exposure in children with pah. clinical studies of bosentan did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. because there is in vitro and in vivo evidence that the main route of excretion of bosentan is biliary, liver impairment could be expected to increase exposure (cmax and auc) of bosentan. the pharmacokinetics of bosentan have not been evaluated in patients with severe liver impairment (child-pugh class c). in patients with moderate hepatic impairment (child-pugh class b), the systemic exposures to bosentan and its active metabolite increased significantly. bosentan should generally be avoided in patients with moderate or severe liver impairment. pharmacokinetics of bosentan were not altered in patients with mild impairment of hepatic function (child-pugh class a) [see dosage and administration (2.6), warnings and precautions (5.1), pharmacokinetics (12.3)] . the effect of renal impairment on the pharmacokinetics of bosentan is small and does not require dosing adjustment [see pharmacokinetics (12.3)] .

Stati Uniti - Ingliż - NLM (National Library of Medicine)

cotherix, inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan is indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1) to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . use of bosentan is contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . coadministration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant use of bosentan and cyclosporine a is contraindi

Stati Uniti - Ingliż - NLM (National Library of Medicine)

denton pharma, inc. dba northwind pharmaceuticals - ciprofloxacin hydrochloride (unii: 4ba73m5e37) (ciprofloxacin - unii:5e8k9i0o4u) - ciprofloxacin tablets are indicated in adult patients for treatment of skin and skin structure infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, proteus vulgaris, providencia stuartii, morganella morganii, citrobacter freundii, pseudomonas aeruginosa, methicillin-susceptible staphylococcus aureus, methicillin-susceptible staphylococcus epidermidis, or streptococcus pyogenes. ciprofloxacin tablets are indicated in adult patients for treatment of bone and joint infections caused by enterobacter cloacae, serratia marcescens, or pseudomonas aeruginosa. ciprofloxacin tablets are indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by escherichia coli, pseudomonas aeruginosa, proteus mirabilis, klebsiella pneumoniae, or bacteroides fragilis.   ciprofloxacin tablets are indicated in adult patients for treatment of infectious diarrhea caused

Stati Uniti - Ingliż - NLM (National Library of Medicine)

liberty pharmaceuticals, inc. - ciprofloxacin hydrochloride (unii: 4ba73m5e37) (ciprofloxacin - unii:5e8k9i0o4u) - ciprofloxacin is indicated in adult patients for treatment of skin and skin structure infections caused by escherichia coli, klebsiella pneumoniae, enterobacter cloacae, proteus mirabilis, proteus vulgaris, providencia stuartii, morganella morganii, citrobacter freundii, pseudomonas aeruginosa, methicillin-susceptible staphylococcus aureus, methicillin-susceptible staphylococcus epidermidis, or streptococcus pyogenes. ciprofloxacin is indicated in adult patients for treatment of bone and joint infections caused by enterobacter cloacae, serratia marcescens, or pseudomonas aeruginosa. ciprofloxacin is indicated in adult patients for treatment of complicated intra-abdominal infections (used in combination with metronidazole) caused by escherichia coli, pseudomonas aeruginosa, proteus mirabilis, klebsiella pneumoniae, or bacteroides fragilis. ciprofloxacin is indicated in adult patients for treatment of i

Stati Uniti - Ingliż - NLM (National Library of Medicine)

alembic pharmaceuticals inc. - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): ·         in adults  to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . use of bosentan tablets are contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan tablets [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . co-administration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant

Stati Uniti - Ingliż - NLM (National Library of Medicine)

alembic pharmaceuticals limited - bosentan (unii: q326023r30) (bosentan anhydrous - unii:xul93r30k2) - bosentan tablets are indicated for the treatment of pulmonary arterial hypertension (pah) (who group 1): ·         in adults  to improve exercise ability and to decrease clinical worsening. studies establishing effectiveness included predominantly patients with who functional class ii-iv symptoms and etiologies of idiopathic or heritable pah (60%), pah associated with connective tissue diseases (21%), and pah associated with congenital heart disease with left-to-right shunts (18%) [see clinical studies (14.1)] . use of bosentan tablets are contraindicated in females who are or may become pregnant. to prevent pregnancy, females of reproductive potential must use two reliable forms of contraception during treatment and for one month after stopping bosentan tablets [see boxed warning, warnings and precautions (5.2), drug interactions (7.2), use in specific populations (8.1)] . co-administration of cyclosporine a and bosentan resulted in markedly increased plasma concentrations of bosentan. therefore, concomitant

Stati Uniti - Ingliż - NLM (National Library of Medicine)

asclemed usa, inc. - meloxicam (unii: vg2qf83cgl) (meloxicam - unii:vg2qf83cgl) - meloxicam tablets are indicated for relief of the signs and symptoms of osteoarthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of rheumatoid arthritis [ see clinical studies ( 14.1) ]. meloxicam tablets are indicated for relief of the signs and symptoms of pauciarticular or polyarticular course juvenile rheumatoid arthritis in patients who weigh ≥60 kg [ see dosage and administration ( 2.4) and clinical studies ( 14.2) ]. meloxicam tablets are contraindicated in the following patients: - known hypersensitivity (e.g., anaphylactic reactions and serious skin reactions) to meloxicam or any components of the drug product [ see warnings and precautions ( 5.7, 5.9) ] - history of asthma, urticaria, or other allergic-type reactions after taking aspirin or other nsaids. severe, sometimes fatal, anaphylactic reactions to nsaids have been reported in such patients [ see wa

Irlanda - Ingliż - HPRA (Health Products Regulatory Authority)

vet-agro multi-trade company sp z o.o. - (s)-methoprene; fipronil - spot-on solution - 67,60.3 mg/pipette - fipronil, combinations

Irlanda - Ingliż - HPRA (Health Products Regulatory Authority)

chanelle pharmaceuticals manufacturing limited - fipronil; (s)-methoprene - spot-on solution - 67, 60.3 mg/pipette - fipronil, combinations

Stati Uniti - Ingliż - NLM (National Library of Medicine)

astrazeneca pharmaceuticals lp - selumetinib (unii: 6uh91i579u) (selumetinib - unii:6uh91i579u) - koselugo is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (nf1) who have symptomatic, inoperable plexiform neurofibromas (pn). none. risk summary based on findings from animal studies and its mechanism of action [see clinical pharmacology (12.1)] , koselugo can cause fetal harm when administered to a pregnant woman. there are no available data on the use of koselugo in pregnant women to evaluate drug-associated risk. in animal reproduction studies, administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryofetal survival at exposures approximately > 5 times the human exposure at the clinical dose of 25 mg/m2 twice daily (see data ). advise pregnant women of the potential risk to the fetus. 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 embryo-fetal development studies in mice at doses > 2.5 mg/kg twice daily (~5-times the human exposure based on area under the curve [auc] at the clinical dose of 25 mg/m2 twice daily), selumetinib caused increases in post-implantation loss, a reduction in mean fetal and litter weights, and an increased occurrence of open eye and cleft palate, but did not induce significant maternal toxicity. administration of selumetinib to pregnant mice from gestation day 6 through lactation day 20 resulted in reduced pup body weights and fewer pups met the pupil constriction criterion on day 21 post-partum. the incidence of malformations (e.g., prematurely open eye(s) and cleft palate) was increased even at the lowest dose of 0.5 mg/kg twice daily (maternal maximal concentration [cmax ] of ~0.6 times the human cmax at the clinical dose of 25 mg/m2 twice daily). risk summary there are no data on the presence of selumetinib or its active metabolite in human milk or their effects on the breastfed child or milk production. selumetinib and its active metabolite were present in the milk of lactating mice (see data ). due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with koselugo and for 1 week after the last dose. data animal data selumetinib and its active metabolite were present in milk from mice dosed with selumetinib throughout gestation and lactation, with a mean plasma/milk ratio of 1.5 in lactating dams dosed at 5 mg/kg twice daily. administration of selumetinib to dams during gestation and early lactation was associated with adverse events in pups, including reduced growth rates and incidence of malformations [see use in specific populations (8.1)]. koselugo can cause fetal harm when administered to a pregnant woman [see use in specific populations (8.1)] . pregnancy testing verify the pregnancy status of females of reproductive potential prior to initiating koselugo [see use in specific populations (8.1)] . contraception females advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. males advise male patients with female partners of reproductive potential to use effective contraception during treatment with koselugo and for 1 week after the last dose. the safety and effectiveness have been established in pediatric patients 2 years of age and older with nf1 who have inoperable pn and the information on this use is discussed throughout the labeling. the safety and effectiveness of koselugo have not been established in pediatric patients younger than 2 years of age. animal toxicity data in 3-month general toxicology studies, male rats receiving selumetinib at doses ≥ 10 mg/kg daily (~60-times the human exposure based on auc at the clinical dose of 25 mg/m2 twice daily) showed growth plate dysplasia. clinical studies did not include patients 65 years of age and older. no dose adjustment is recommended in patients with renal impairment or those with end stage renal disease [see clinical pharmacology (12.3)]. selumetinib exposures increased in patients with moderate or severe hepatic impairment [see clinical pharmacology (12.3)] . reduce the dose of koselugo for patients with moderate hepatic impairment (child-pugh b). a recommended dosage of koselugo for use in patients with severe hepatic impairment (child-pugh c) has not been established [see dosage and administration (2.3)] .