Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - fluticasone furoate (unii: js86977wnv) (fluticasone - unii:cut2w21n7u), umeclidinium bromide (unii: 7an603v4jv) (umeclidinium - unii:ge2t1418sv), vilanterol trifenatate (unii: 40aho2c6dg) (vilanterol - unii:028lzy775b) - fluticasone furoate 100 ug - trelegy ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). trelegy ellipta is indicated for the maintenance treatment of asthma in patients aged 18 years and older. trelegy ellipta is not indicated for the relief of acute bronchospasm. trelegy ellipta is contraindicated in the following conditions: risk summary there are insufficient data on the use of trelegy ellipta or its individual components, fluticasone furoate, umeclidinium, and vilanterol, in pregnant women to inform a drug‑associated risk. (see clinical considerations.) in an animal reproduction study, fluticasone furoate and vilanterol administered by inhalation alone or in combination to pregnant rats during the period of organogenesis produced no fetal structural abnormalities. the highest fluticasone furoate and vilanterol doses in this study were approximately 4.5 and 40 times the maximum recommended human daily inhalation doses (mrhdid) of 200 and 25 mcg, respectively in adults. (see data.) umeclidinium administered via inhalation or subcutaneously to pregnant rats and rabbits was not associated with adverse effect on embryofetal development at exposures approximately 40 and 150 times, respectively, the human exposure at the mrhdid of 62.5 mcg. (see data.) the estimated risk of major birth defects and miscarriage for the indicated populations is unknown. in the u.s. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. clinical considerations disease-associated maternal and/or embryofetal risk: in women with poorly or moderately controlled asthma, there is an increased risk of several perinatal outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma. labor or delivery: trelegy ellipta should be used during late gestation and labor only if the potential benefit justifies the potential for risks related to beta-agonists interfering with uterine contractility. data animal data: the combination of fluticasone furoate, umeclidinium, and vilanterol has not been studied in pregnant animals. studies in pregnant animals have been conducted with fluticasone furoate and vilanterol in combination and individually with fluticasone furoate, umeclidinium, or vilanterol. fluticasone furoate and vilanterol: in an embryofetal developmental study, pregnant rats received fluticasone furoate and vilanterol during the period of organogenesis at doses up to approximately 4.5 and 40 times the mrhdid of 200 and 25 mcg, respectively, alone or in combination (on a mcg/m2 basis at inhalation doses up to approximately 95 mcg/kg/day). no evidence of structural abnormalities was observed. fluticasone furoate: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received fluticasone furoate during the period of organogenesis at doses up to approximately 4.5 times and equal to, respectively, the mrhdid of 200 mcg (on a mcg/m2 basis at maternal inhalation doses up to 91 and 8 mcg/kg/day, respectively). no evidence of structural abnormalities in fetuses was observed in either species. in a perinatal and postnatal developmental study in rats, dams received fluticasone furoate during late gestation and lactation periods at doses up to approximately 1.5 times the mrhdid of 200 mcg (on a mcg/m2 basis at maternal inhalation doses up to 27 mcg/kg/day). no evidence of effects on offspring development was observed. umeclidinium: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received umeclidinium during the period of organogenesis at doses up to approximately 40 and 150 times, respectively the mrhdid of 62.5 mcg (on an auc basis at maternal inhalation doses up to 278 mcg/kg/day in rats and at maternal subcutaneous doses up to 180 mcg/kg/day in rabbits). no evidence of teratogenic effects was observed in either species. in a perinatal and postnatal developmental study in rats, dams received umeclidinium during late gestation and lactation periods at doses up to approximately 20 times the mrhdid (on an auc basis at maternal subcutaneous doses up to 60 mcg/kg/day). no evidence of effects on offspring development was observed. vilanterol: in 2 separate embryofetal developmental studies, pregnant rats and rabbits received vilanterol during the period of organogenesis at doses up to approximately 13,000 and 760 times, respectively, the mrhdid (on a mcg/m2 basis at maternal inhalation doses up to 33,700 mcg/kg/day in rats and on an auc basis at maternal inhaled doses up to 5,740 mcg/kg/day in rabbits). no evidence of structural abnormalities was observed at any dose in rats or in rabbits up to approximately 120 times the mrhdid (on an auc basis at maternal doses up to 591 mcg/kg/day). however, fetal skeletal variations were observed in rabbits at approximately 760 or 840 times the mrhdid (on an auc basis at maternal inhaled or subcutaneous doses of 5,740 or 300 mcg/kg/day, respectively). the skeletal variations included decreased or absent ossification in cervical vertebral centrum and metacarpals. in a perinatal and postnatal developmental study in rats, dams received vilanterol during late gestation and the lactation periods at doses up to approximately 3,900 times the mrhdid (on a mcg/m2 basis at maternal oral doses up to 10,000 mcg/kg/day). no evidence of effects in offspring development was observed. risk summary there is no information available on the presence of fluticasone furoate, umeclidinium, or vilanterol in human milk; the effects on the breastfed child; or the effects on milk production. umeclidinium was detected in the plasma of offspring of lactating rats treated with umeclidinium, suggesting its presence in maternal milk. (see data.) the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for trelegy ellipta and any potential adverse effects on the breastfed child from fluticasone furoate, umeclidinium, or vilanterol or from the underlying maternal condition. data subcutaneous administration of umeclidinium to lactating rats at greater than or equal to 60 mcg/kg/day resulted in a quantifiable level of umeclidinium in 2 of 54 pups, which may indicate transfer of umeclidinium in rat milk. the safety and effectiveness of trelegy ellipta have not been established in pediatric patients (aged 17 years and younger). trelegy ellipta is not indicated for use in pediatric patients. effects on growth orally inhaled corticosteroids may cause a reduction in growth velocity when administered to children and adolescents. controlled clinical trials have shown that ics may cause a reduction in growth in children. in these trials, the mean reduction in growth velocity was approximately 1 cm/year (range: 0.3 to 1.8 cm/year) and appears to be related to dose and duration of exposure. this effect has been observed in the absence of laboratory evidence of hpa axis suppression, suggesting that growth velocity is a more sensitive indicator of systemic corticosteroid exposure in children than some commonly used tests of hpa axis function. the long-term effects of this reduction in growth velocity associated with orally inhaled corticosteroids, including the impact on final adult height, are unknown. a randomized, double-blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with 110 mcg of fluticasone furoate in the nasal spray formulation on growth velocity assessed by stadiometry. the subjects were 474 prepubescent children (girls aged 5 to 7.5 years and boys aged 5 to 8.5 years). mean growth velocity over the 52-week treatment period was lower in the subjects receiving fluticasone furoate nasal spray (5.19 cm/year) compared with placebo (5.46 cm/year). the mean reduction in growth velocity was 0.27 cm/year (95% ci: 0.06, 0.48) [see warnings and precautions (5.18)] . based on available data, no adjustment of the dosage of trelegy ellipta in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out. in copd trials 1 and 2 (coadministration trials), 189 subjects aged 65 years and older, of which 39 subjects were aged 75 years and older, were administered umeclidinium 62.5 mcg + fluticasone furoate/vilanterol 100/25 mcg. in copd trial 3, 2,265 subjects aged 65 years and older, of which 565 subjects were aged 75 years and older, were administered trelegy ellipta. in an asthma clinical trial (trial 4), 159 subjects aged 65 years and older, of which 27 subjects were aged 75 years and older, were administered trelegy ellipta 100/62.5/25 mcg or trelegy ellipta 200/62.5/25 mcg. 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 subjects. trelegy ellipta has not been studied in subjects with hepatic impairment. information on the individual components is provided below. fluticasone furoate/vilanterol fluticasone furoate systemic exposure increased by up to 3-fold in subjects with hepatic impairment compared with healthy subjects. hepatic impairment had no effect on vilanterol systemic exposure. use trelegy ellipta with caution in patients with moderate or severe hepatic impairment. monitor patients for corticosteroid-related side effects [see clinical pharmacology (12.3)] . umeclidinium patients with moderate hepatic impairment (child-pugh score of 7-9) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with moderate hepatic impairment and their healthy controls. studies in subjects with severe hepatic impairment have not been performed [see clinical pharmacology (12.3)] . trelegy ellipta has not been studied in subjects with renal impairment. information on the individual components is provided below. fluticasone furoate/vilanterol there were no significant increases in either fluticasone furoate or vilanterol exposure in subjects with severe renal impairment (crcl <30 ml/min) compared with healthy subjects. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] . umeclidinium patients with severe renal impairment (crcl <30 ml/min) showed no relevant increases in cmax or auc, nor did protein binding differ between subjects with severe renal impairment and their healthy controls. no dosage adjustment is required in patients with renal impairment [see clinical pharmacology (12.3)] .

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - sumatriptan succinate (unii: j8bdz68989) (sumatriptan - unii:8r78f6l9vo) - sumatriptan 4 mg in 0.5 ml - imitrex injection is indicated in adults for (1) the acute treatment of migraine, with or without aura, and (2) the acute treatment of cluster headache. limitations of use imitrex injection is contraindicated in patients with: risk summary data from a prospective pregnancy exposure registry and epidemiological studies of pregnant women have not detected an increased frequency of birth defects or a consistent pattern of birth defects among women exposed to sumatriptan compared with the general population (see data) . in developmental toxicity studies in rats and rabbits, oral administration of sumatriptan to pregnant animals was associated with embryolethality, fetal abnormalities, and pup mortality. when administered by the intravenous route to pregnant rabbits, sumatriptan was embryolethal (see data) . in the u.s. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. the reported rate of major

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - fluticasone furoate (unii: js86977wnv) (fluticasone - unii:cut2w21n7u), vilanterol trifenatate (unii: 40aho2c6dg) (vilanterol - unii:028lzy775b) - fluticasone furoate 100 ug - breo ellipta is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (copd). breo ellipta is indicated for the maintenance treatment of asthma in patients aged 5 years and older. breo ellipta is not indicated for the relief of acute bronchospasm. breo ellipta is contraindicated in the following conditions: risk summary there are insufficient data on the use of breo ellipta or its individual components, fluticasone furoate and vilanterol, in pregnant women to inform a drug-associated risk. (see clinical considerations.) in an animal reproduction study, fluticasone furoate and vilanterol administered by inhalation alone or in combination to pregnant rats during the period of organogenesis produced no fetal structural abnormalities. the highest fluticasone furoate and vilanterol doses in this study were approximately 5 and 40 times the maximum recommended human daily inhalation doses (mrhdid) of 200 and 25 mcg, respectively. (see data.) the estimated risk of major birth

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - carvedilol phosphate (unii: eqt531s367) (carvedilol - unii:0k47ul67f2) - carvedilol phosphate 10 mg - coreg cr is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ace inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see drug interactions (7.4), clinical studies (14.1)] . coreg cr is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of less than or equal to 40% (with or without symptomatic heart failure) [see clinical studies (14.2)] . coreg cr is indicated for the management of essential hypertension [see clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide‑type diuretics [see drug interactions (7.2)] . coreg cr is contraindicated in the following conditions: risk summary available data regarding use of coreg cr in pregnant women are insufficient to determine whether

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - carvedilol (unii: 0k47ul67f2) (carvedilol - unii:0k47ul67f2) - carvedilol 3.125 mg - coreg is indicated for the treatment of mild-to-severe chronic heart failure of ischemic or cardiomyopathic origin, usually in addition to diuretics, ace inhibitors, and digitalis, to increase survival and, also, to reduce the risk of hospitalization [see drug interactions (7.4), clinical studies (14.1)] . coreg is indicated to reduce cardiovascular mortality in clinically stable patients who have survived the acute phase of a myocardial infarction and have a left ventricular ejection fraction of less than or equal to 40% (with or without symptomatic heart failure) [see clinical studies (14.2)] . coreg is indicated for the management of essential hypertension [see clinical studies (14.3, 14.4)] . it can be used alone or in combination with other antihypertensive agents, especially thiazide-type diuretics [see drug interactions (7.2)] . coreg is contraindicated in the following conditions: risk summary available data regarding use of coreg in pregnant women are insufficient to determine whether there are drug-

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - atovaquone (unii: y883p1z2lt) (atovaquone - unii:y883p1z2lt) - atovaquone 750 mg in 5 ml - mepron oral suspension is indicated for the prevention of pneumocystis jirovecii pneumonia (pcp) in adults and adolescents (aged 13 years and older) who cannot tolerate trimethoprim-sulfamethoxazole (tmp-smx). mepron oral suspension is indicated for the acute oral treatment of mild-to-moderate pcp in adults and adolescents (aged 13 years and older) who cannot tolerate tmp-smx. clinical experience with mepron for the treatment of pcp has been limited to subjects with mild-to-moderate pcp (alveolar-arterial oxygen diffusion gradient [(a-a)do2 ] ≤45 mm hg). treatment of more severe episodes of pcp with mepron has not been studied. the efficacy of mepron in subjects who are failing therapy with tmp-smx has also not been studied. mepron oral suspension is contraindicated in patients who develop or have a history of hypersensitivity reactions (e.g., angioedema, bronchospasm, throat tightness, urticaria) to atovaquone or any of the components of mepron. risk summary available data from postmarketing experience with

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - dutasteride (unii: o0j6xjn02i) (dutasteride - unii:o0j6xjn02i), tamsulosin hydrochloride (unii: 11sv1951mr) (tamsulosin - unii:g3p28oml5i) - dutasteride 0.5 mg - jalyn (dutasteride and tamsulosin hydrochloride) capsules are indicated for the treatment of symptomatic bph in men with an enlarged prostate. dutasteride-containing products, including jalyn, are not approved for the prevention of prostate cancer. jalyn is contraindicated for use in: •   pregnancy. dutasteride use is contraindicated in females who are pregnant. in animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. therefore, jalyn may cause fetal harm when administered to a pregnant female [see warnings and precautions ( 5.6), use in specific populations ( 8.1)] . •   patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema, urticaria, pruritus, respiratory symptoms) to dutasteride, other 5-alpha-reductase inhibitors, tamsulosin, or any other component of jalyn [see adverse reactions (6.2) ] . risk summary jalyn is contraindicated for use in pregnancy because it may cause

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - dutasteride (unii: o0j6xjn02i) (dutasteride - unii:o0j6xjn02i) - dutasteride 0.5 mg - avodart (dutasteride) soft gelatin capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (bph) in men with an enlarged prostate to: avodart in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic bph in men with an enlarged prostate. avodart is not approved for the prevention of prostate cancer. avodart is contraindicated for use in: risk summary avodart is contraindicated for use in pregnancy because it may cause harm to the male fetus [see contraindications (4)] . avodart is not indicated for use in women. avodart 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 populat

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - mepolizumab (unii: 90z2uf0e52) (mepolizumab - unii:90z2uf0e52) - mepolizumab 100 mg in 1 ml - nucala is indicated for the add-on maintenance treatment of adult and pediatric patients aged 6 years and older with severe asthma and with an eosinophilic phenotype [see use in specific populations (8.4), clinical studies (14.1)] . limitations of use nucala is not indicated for the relief of acute bronchospasm or status asthmaticus. nucala is indicated for the add-on maintenance treatment of chronic rhinosinusitis with nasal polyps (crswnp) in adult patients 18 years of age and older with inadequate response to nasal corticosteroids. nucala is indicated for the treatment of adult patients with eosinophilic granulomatosis with polyangiitis (egpa). nucala is indicated for the treatment of adult and pediatric patients aged 12 years and older with hypereosinophilic syndrome (hes) for ≥6 months without an identifiable non-hematologic secondary cause. nucala is contraindicated in patients with a history of hypersensitivity to mepolizumab or excipients in the formulation [see warnings and precautions (5.1), descrip

Amerika Serikat - Inggris - NLM (National Library of Medicine)

glaxosmithkline llc - atovaquone (unii: y883p1z2lt) (atovaquone - unii:y883p1z2lt), proguanil hydrochloride (unii: r71y86m0wt) (proguanil - unii:s61k3p7b2v) - atovaquone 250 mg - malarone is indicated for the prophylaxis of plasmodium falciparum malaria, including in areas where chloroquine resistance has been reported. malarone is indicated for the treatment of acute, uncomplicated p. falciparum malaria. malarone has been shown to be effective in regions where the drugs chloroquine, halofantrine, mefloquine, and amodiaquine may have unacceptable failure rates, presumably due to drug resistance. risk summary available data from published literature and postmarketing experience with use of malarone in pregnant women are insufficient to identify a drug-associated risk for major birth defects, miscarriage, or adverse maternal or fetal outcomes. the proguanil component of malarone acts to inhibit parasitic dihydrofolate reductase; however, pregnant women and females of reproductive potential should continue folate supplementation to prevent neural tube defects [see clinical pharmacology (12.4)] . pregnant women with malaria are at increased risk for adverse pregnancy outcomes (see clin