Australia - English - Department of Health (Therapeutic Goods Administration)

roche diagnostics australia pty limited - ct1056 - immunohistology cell marker ivds - immunohistochemical staining of tissues for mmr status as an aid in identifying patients eligible for treatment with nominated therapies in selected indications ventana anti-pms2 (a16-4) mouse monoclonal primary antibody is intended for use in the assessment of mismatch repair (mmr) protein pms2 in formalin-fixed, paraffin-embedded tissue specimens stained on a ventana benchmark ultra and benchmark ultra plus instrument. this antibody is one of the components of ventana mmr rxdx panel that is indicated as an aid in identifying patients eligible for treatment with pembrolizumab in deficient mmr solid tumours, and a combination of pembrolizumab and lenvatinib in proficient mmr endometrial carcinoma.

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

puretek corporation - .alpha.-tocopherol acetate, dl- (unii: wr1wpi7ew8) (.alpha.-tocopherol, dl- - unii:7qwa1rio01), magnesium oxide (unii: 3a3u0gi71g) (magnesium cation - unii:t6v3lhy838), chromium nicotinate (unii: a150ay412v) (chromic cation - unii:x1n4508kf1), pyridoxine hydrochloride (unii: 68y4cf58bv) (pyridoxine - unii:kv2jz1bi6z), molybdenum (unii: 81ah48963u) (molybdenum - unii:81ah48963u), selenium (unii: h6241uj22b) (selenium - unii:h6241uj22b), cholecalciferol (unii: 1c6v77qf41) (cholecalciferol - unii:1c6v77 - vitrexyl™ is indicated to provide vitamin supplement to men and women. folic acid is effective in the treatment of megaloblastic anemias due to a deficiency of folic acid (as may be seen in tropical or nontropical sprue) and in anemias of nutritional origin, pregnancy, infancy, or childhood. this product is contraindicated in patients with a known hypersensitivity to any of the ingredients.

Israel - English - Ministry of Health

novartis israel ltd - valsartan - film coated tablets - valsartan 80 mg - valsartan - valsartan - for treatment of hypertension. diovan is indicated for the treatment of heart failure (nyha class ii-iv) in patients who are intolerant of angiotensin converting enzyme inhibitors. in a controlled clinical trial diovan signicantly reduced hospitalisations for heart failure. there is no evidence that diovan provides added benefits when it is used with an adequate dose of an ace inhibitor. diovan is indicated to improve survival following myocardial infarction in clinically stable patients with signs symptoms or radiological evidence of left ventricular failure and /or with left ventricular systolic dysfunction.

Israel - English - Ministry of Health

novartis israel ltd - valsartan - film coated tablets - valsartan 160 mg - valsartan - valsartan - for treatment of hypertension. diovan is indicated for the treatment of heart failure (nyha class ii-iv) in patients who are intolerant of angiotensin converting enzyme inhibitors. in a controlled clinical trial diovan signicantly reduced hospitalisations for heart failure. there is no evidence that diovan provides added benefits when it is used with an adequate dose of an ace inhibitor. diovan is indicated to improve survival following myocardial infarction in clinically stable patients with signs symptoms or radiological evidence of left ventricular failure and /or with left ventricular systolic dysfunction.

Israel - English - Ministry of Health

novartis israel ltd - valsartan - film coated tablets - valsartan 40 mg - valsartan - valsartan - diovan is indicated for the treatment of heart failure (nyha class ii-iv) in patients who are intolerant of angiotensin converting enzyme inhibitors. in a controlled clinical trial diovan significantly reduced hospitalisations for heart failure. there is no evidence that diovan provides added benefits when it is used with an adequate dose of an ace inhibitor. diovan is indicated to improve survival following myocardial infarction in clinically stable patients with signs symptoms or radiological evidence of left ventricular failure and /or with left ventricular systolic dysfunction.

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

torrent pharmaceuticals limited - tadalafil (unii: 742sxx0ict) (tadalafil - unii:742sxx0ict) - tadalafil tablets are indicated for the treatment of erectile dysfunction (ed). tadalafil tablets are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (bph). tadalafil tablets are indicated for the treatment of ed and the signs and symptoms of bph (ed/bph).       if tadalafil tablets are used with finasteride to initiate bph treatment, such use is recommended for up to 26 weeks because the incremental benefit of tadalafil decreases from 4 weeks until 26 weeks, and the incremental benefit of tadalafil beyond 26 weeks is unknown [see clinical studies (14.3)] . administration of tadalafil to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. in clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates [see clinical pharmacology (12.2)] . tadalafil is contraindicated in patients with a known serious hypersensitivity to tadalafil (tadalafil tablets or adcirca ® ). hypersensiti

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

aphena pharma solutions - tennessee, llc - tadalafil (unii: 742sxx0ict) (tadalafil - unii:742sxx0ict) - tadalafil tablets are indicated for the treatment of erectile dysfunction (ed). tadalafil tablets are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (bph). tadalafil tablets are indicated for the treatment of ed and the signs and symptoms of bph (ed/bph).       if tadalafil tablets are used with finasteride to initiate bph treatment, such use is recommended for up to 26 weeks because the incremental benefit of tadalafil decreases from 4 weeks until 26 weeks, and the incremental benefit of tadalafil beyond 26 weeks is unknown [see clinical studies (14.3)] . administration of tadalafil to patients who are using any form of organic nitrate, either regularly and/or intermittently, is contraindicated. in clinical pharmacology studies, tadalafil was shown to potentiate the hypotensive effect of nitrates [see clinical pharmacology (12.2)] . tadalafil is contraindicated in patients with a known serious hypersensitivity to tadalafil (tadalafil tablets or adcirca® ). hypersensitiv

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

lupin pharmaceuticals, inc. - atorvastatin calcium trihydrate (unii: 48a5m73z4q) (atorvastatin - unii:a0jwa85v8f) - atorvastatin calcium is indicated: - to reduce the risk of. myocardial infarction (mi), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (chd) but without clinically evident chd. mi and stroke in adults with type 2 diabetes mellitus with multiple risk factors for chd but without clinically evident chd. non-fatal mi, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident chd. - myocardial infarction (mi), stroke, revascularization procedures, and angina in adults with multiple risk factors for coronary heart disease (chd) but without clinically evident chd. - mi and stroke in adults with type 2 diabetes mellitus with multiple risk factors for chd but without clinically evident chd. - non-fatal mi, fatal and non-fatal stroke, revascularization procedures, hospitalization for congestive heart failure, and angina in adults with clinically evident chd. - as an adjunct to diet to reduce low-density lipoprotein cholesterol (ldl-c) in: adults with primary hyperlipidemia. adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - adults with primary hyperlipidemia. - adults and pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (hefh). - as an adjunct to other ldl-c-lowering therapies, or alone if such treatments are unavailable, to reduce ldl-c in adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (hofh). - as an adjunct to diet for the treatment of adults with: primary dysbetalipoproteinemia. hypertriglyceridemia. - primary dysbetalipoproteinemia. - hypertriglyceridemia. - acute liver failure or decompensated cirrhosis [see warnings and precautions (5.3)] - hypersensitivity to atorvastatin or any excipients in atorvastatin calcium. hypersensitivity reactions, including anaphylaxis, angioneurotic edema, erythema multiforme, stevens-johnson syndrome, and toxic epidermal necrolysis, have been reported [see adverse reactions (6.2)] . risk summary discontinue atorvastatin calcium when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. atorvastatin calcium decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, atorvastatin calcium may cause fetal harm when administered to pregnant patients based on the mechanism of action [see clinical pharmacology (12.1)] . in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with atorvastatin calcium use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered atorvastatin at doses that resulted in up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (mrhd) of 80 mg, based on body surface area (mg/m2 ). in rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development delay were observed at doses ≥ 6 times the mrhd (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data: a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. animal data: atorvastatin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day, respectively. atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. these doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure at the mrhd based on surface area (mg/m2 ). in rats, the maternally toxic dose of 300 mg/kg resulted in increased post-implantation loss and decreased fetal body weight. at the maternally toxic doses of 50 and 100 mg/kg/day in rabbits, there was increased post-implantation loss, and at 100 mg/kg/day fetal body weights were decreased. in a study in pregnant rats administered 20, 100, or 225 mg/kg/day from gestation day 7 through to lactation day 20 (weaning), there was decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups of mothers dosed with 225 mg/kg/day, a dose at which maternal toxicity was observed. pup body weight was decreased through postnatal day 21 at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. pup development was delayed (rotarod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). these doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human exposure at the mrhd, based on auc. atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. risk summary there is no information about the presence of atorvastatin in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. studies in rats have shown that atorvastatin and/or its metabolites are present in the breast milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk (see data) . statins, including atorvastatin calcium, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with atorvastatin calcium [see use in specific populations (8.1), clinical pharmacology (12.1)] . data following a single oral administration of 10 mg/kg of radioactive atorvastatin to lactating rats, the concentration of total radioactivity was determined. atorvastatin and/or its metabolites were measured in the breast milk and pup plasma at a 2:1 ratio (milk:plasma). the safety and effectiveness of atorvastatin calcium as an adjunct to diet to reduce ldl-c have been established pediatric patients 10 years of age and older with hefh. use of atorvastatin calcium for this indication is based on a double-blind, placebo-controlled clinical trial in 187 pediatric patients 10 years of age and older with hefh. in this limited controlled trial, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of atorvastatin calcium as an adjunct to other ldl-c-lowering therapies to reduce ldl-c have been established pediatric patients 10 years of age and older with hofh. use of atorvastatin calcium for this indication is based on a trial without a concurrent control group in 8 pediatric patients 10 years of age and older with hofh [see clinical studies (14)] . the safety and effectiveness of atorvastatin calcium have not been established in pediatric patients younger than 10 years of age with hefh or hofh, or in pediatric patients with other types of hyperlipidemia (other than hefh or hofh). of the total number of atorvastatin calcium -treated patients in clinical trials, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. no overall differences in safety or effectiveness were observed between these patients and younger patients advanced age (≥65 years) is a risk factor for atorvastatin calcium -associated myopathy and rhabdomyolysis. dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. monitor geriatric patients receiving atorvastatin calcium for the increased risk of myopathy [see warnings and precautions (5.1) and clinical pharmacology (12.3)] . renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. renal impairment does not affect the plasma concentrations of atorvastatin calcium, therefore there is no dosage adjustment in patients with renal impairment [see warnings and precautions (5.1) and clinical pharmacology (12.3)]. in patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin calcium are markedly increased. cmax and auc are each 4-fold greater in patients with childs-pugh a disease. cmax and auc are approximately 16-fold and 11-fold increased, respectively, in patients with childs-pugh b disease. atorvastatin calcium is contraindicated in patients with acute liver failure or decompensated cirrhosis [see contraindications (4)] .

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

preferred pharmaceuticals, inc. - atorvastatin calcium trihydrate (unii: 48a5m73z4q) (atorvastatin - unii:a0jwa85v8f) - atorvastatin calcium is indicated: risk summary discontinue atorvastatin calcium when pregnancy is recognized. alternatively, consider the ongoing therapeutic needs of the individual patient. atorvastatin calcium decreases synthesis of cholesterol and possibly other biologically active substances derived from cholesterol; therefore, atorvastatin calcium may cause fetal harm when administered to pregnant patients based on the mechanism of action [see clinical pharmacology (12.1)] . in addition, treatment of hyperlipidemia is not generally necessary during pregnancy. atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. available data from case series and prospective and retrospective observational cohort studies over decades of use with statins in pregnant women have not identified a drug-associated risk of major congenital malformations. published data from prospective and retrospective observational cohort studies with atorvastatin calcium use in pregnant women are insufficient to determine if there is a drug-associated risk of miscarriage (see data) . in animal reproduction studies, no adverse developmental effects were observed in pregnant rats or rabbits orally administered atorvastatin at doses that resulted in up to 30 and 20 times, respectively, the human exposure at the maximum recommended human dose (mrhd) of 80 mg, based on body surface area (mg/m2 ). in rats administered atorvastatin during gestation and lactation, decreased postnatal growth and development delay were observed at doses ≥ 6 times the mrhd (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. data human data: a medicaid cohort linkage study of 1152 statin-exposed pregnant women compared to 886,996 controls did not find a significant teratogenic effect from maternal use of statins in the first trimester of pregnancy, after adjusting for potential confounders – including maternal age, diabetes mellitus, hypertension, obesity, and alcohol and tobacco use – using propensity score-based methods. the relative risk of congenital malformations between the group with statin use and the group with no statin use in the first trimester was 1.07 (95% confidence interval 0.85 to 1.37) after controlling for confounders, particularly pre-existing diabetes mellitus. there were also no statistically significant increases in any of the organ-specific malformations assessed after accounting for confounders. in the majority of pregnancies, statin treatment was initiated prior to pregnancy and was discontinued at some point in the first trimester when pregnancy was identified. study limitations include reliance on physician coding to define the presence of a malformation, lack of control for certain confounders such as body mass index, use of prescription dispensing as verification for the use of a statin, and lack of information on non-live births. animal data: atorvastatin was administered to pregnant rats and rabbits during organogenesis at oral doses up to 300 mg/kg/day and 100 mg/kg/day, respectively. atorvastatin was not teratogenic in rats at doses up to 300 mg/kg/day or in rabbits at doses up to 100 mg/kg/day. these doses resulted in multiples of about 30 times (rat) or 20 times (rabbit) the human exposure at the mrhd based on surface area (mg/m2 ). in rats, the maternally toxic dose of 300 mg/kg resulted in increased post-implantation loss and decreased fetal body weight. at the maternally toxic doses of 50 and 100 mg/kg/day in rabbits, there was increased post-implantation loss, and at 100 mg/kg/day fetal body weights were decreased. in a study in pregnant rats administered 20, 100, or 225 mg/kg/day from gestation day 7 through to lactation day 20 (weaning), there was decreased survival at birth, postnatal day 4, weaning, and post-weaning in pups of mothers dosed with 225 mg/kg/day, a dose at which maternal toxicity was observed. pup body weight was decreased through postnatal day 21 at 100 mg/kg/day, and through postnatal day 91 at 225 mg/kg/day. pup development was delayed (rotarod performance at 100 mg/kg/day and acoustic startle at 225 mg/kg/day; pinnae detachment and eye-opening at 225 mg/kg/day). these doses correspond to 6 times (100 mg/kg) and 22 times (225 mg/kg) the human exposure at the mrhd, based on auc. atorvastatin crosses the rat placenta and reaches a level in fetal liver equivalent to that of maternal plasma. risk summary there is no information about the presence of atorvastatin in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production. however, it has been shown that another drug in this class passes into human milk. studies in rats have shown that atorvastatin and/or its metabolites are present in the breast milk of lactating rats. when a drug is present in animal milk, it is likely that the drug will be present in human milk (see data) . statins, including atorvastatin calcium, decrease cholesterol synthesis and possibly the synthesis of other biologically active substances derived from cholesterol and may cause harm to the breastfed infant. because of the potential for serious adverse reactions in a breastfed infant, based on the mechanism of action, advise patients that breastfeeding is not recommended during treatment with atorvastatin calcium [see use in specific populations (8.1), clinical pharmacology (12.1)] . data following a single oral administration of 10 mg/kg of radioactive atorvastatin to lactating rats, the concentration of total radioactivity was determined. atorvastatin and/or its metabolites were measured in the breast milk and pup plasma at a 2:1 ratio (milk:plasma). the safety and effectiveness of atorvastatin calcium as an adjunct to diet to reduce ldl-c have been established pediatric patients 10 years of age and older with hefh. use of atorvastatin calcium for this indication is based on a double-blind, placebo-controlled clinical trial in 187 pediatric patients 10 years of age and older with hefh. in this limited controlled trial, there was no significant effect on growth or sexual maturation in the boys or girls, or on menstrual cycle length in girls. the safety and effectiveness of atorvastatin calcium as an adjunct to other ldl-c-lowering therapies to reduce ldl-c have been established pediatric patients 10 years of age and older with hofh. use of atorvastatin calcium for this indication is based on a trial without a concurrent control group in 8 pediatric patients 10 years of age and older with hofh [see clinical studies (14)] . the safety and effectiveness of atorvastatin calcium have not been established in pediatric patients younger than 10 years of age with hefh or hofh, or in pediatric patients with other types of hyperlipidemia (other than hefh or hofh). of the total number of atorvastatin calcium -treated patients in clinical trials, 15,813 (40%) were ≥65 years old and 2,800 (7%) were ≥75 years old. no overall differences in safety or effectiveness were observed between these patients and younger patients advanced age (≥65 years) is a risk factor for atorvastatin calcium -associated myopathy and rhabdomyolysis. dose selection for an elderly patient should be cautious, recognizing the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy and the higher risk of myopathy. monitor geriatric patients receiving atorvastatin calcium for the increased risk of myopathy [see warnings and precautions (5.1) and clinical pharmacology (12.3)] . renal impairment is a risk factor for myopathy and rhabdomyolysis. monitor all patients with renal impairment for development of myopathy. renal impairment does not affect the plasma concentrations of atorvastatin calcium, therefore there is no dosage adjustment in patients with renal impairment [see warnings and precautions (5.1) and clinical pharmacology (12.3)]. in patients with chronic alcoholic liver disease, plasma concentrations of atorvastatin calcium are markedly increased. cmax and auc are each 4-fold greater in patients with childs-pugh a disease. cmax and auc are approximately 16-fold and 11-fold increased, respectively, in patients with childs-pugh b disease. atorvastatin calcium is contraindicated in patients with acute liver failure or decompensated cirrhosis [see contraindications (4)] .

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

directrx - atorvastatin calcium trihydrate (unii: 48a5m73z4q) (atorvastatin - unii:a0jwa85v8f) - active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels hypersensitivity to any component of this medication pregnancy [see use in specific population s(8.1, 8.3)]. lactation [see use in specific population s(8.2)]. therapy with lipid-altering agents should be only one component of multiple risk factor intervention in individuals at significantly increased risk for atherosclerotic vascular disease due to hypercholesterolemia. drug therapy is recommended as an adjunct to diet when the response to a diet restricted in saturated fat and cholesterol and other nonpharmacologic measures alone has been inadequate. in patients with chd or multiple risk factors for chd, atorvastatin calcium tablets can be started simultaneously with diet. 1.1 prevention of cardiovascular disease in adults in adult patients without clinically evident coronary heart disease, but with multiple risk factors for coronary heart disease such as age, smoking, hypertension, l