新西兰 - 英文 - Medsafe (Medicines Safety Authority)

janssen-cilag (new zealand) ltd - collagenase clostridium histolyticum 900ug;   - powder for injection - 900 mcg - active: collagenase clostridium histolyticum 900ug   excipient: hydrochloric acid sucrose trometamol calcium chloride dihydrate sodium chloride water for injection - xiaflex is indicated for the treatment of dupuytren's contracture in adult patients with palpable cord.

美国 - 英文 - NLM (National Library of Medicine)

bryant ranch prepack - valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - valsartan 160 mg - valsartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including hydrochlorothiazide and the angiotensin ii receptor blocker (arb) class to which valsartan principally belongs. there are no controlled trials demonstrating risk reduction with valsartan and hydrochlorothiazide tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality have also been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. add-on therapy valsartan and hydrochlorothiazide tablets may be used in patients whose blood pressure is not adequately controlled on monotherapy. replacement therapy valsartan and hydrochlorothiazide tablets may be substituted for the titrated components.  initial therapy valsartan and hydrochlorothiazide tablets may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals. the choice of valsartan and hydrochlorothiazide tablets as initial therapy for hypertension should be based on an assessment of potential benefits and risks. patients with stage 2 hypertension are at a relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal and the incremental likelihood of achieving goal with a combination compared to monotherapy. individual blood pressure goals may vary based upon the patient's risk. data from the high dose multifactorial trial [see clinical studies (14.1)] provides estimates of the probability of reaching a target blood pressure with valsartan and hydrochlorothiazide tablets compared to valsartan or hydrochlorothiazide monotherapy. the figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with valsartan and hydrochlorothiazide tablets 320/25 mg, based upon baseline systolic or diastolic blood pressure. the curve of each treatment group was estimated by logistic regression modeling. the estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. figure 1: probability of achieving systolic blood pressure <140 mmhg at week 8 figure 2: probability of achieving diastolic blood pressure <90 mmhg at week 8 figure 3: probability of achieving systolic blood pressure <130 mmhg at week 8 figure 4: probability of achieving diastolic blood pressure <80 mmhg at week 8 for example, a patient with a baseline blood pressure of 160/100 mmhg has about a 41% likelihood of achieving a goal of < 140 mmhg (systolic) and 60% likelihood of achieving < 90 mmhg (diastolic) on valsartan alone and the likelihood of achieving these goals on hctz alone is about 50% (systolic) or 57% (diastolic). the likelihood of achieving these goals on valsartan and hydrochlorothiazide tablets rises to about 84% (systolic) or 80% (diastolic). the likelihood of achieving these goals on placebo is about 23% (systolic) or 36% (diastolic). valsartan and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to any component of this product. because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. do not coadminister aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes [see drug interactions (7)]. risk summary valsartan and hydrochlorothiazide tablet can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. published reports include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan (see clinical considerations). when pregnancy is detected discontinue valsartan and hydrochlorothiazide tablet as soon as possible. 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 2-4% and 1520%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions valsartan oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative drug treatment. closely observe neonates with histories of in utero exposure to valsartan and hydrochlorothiazide tablet for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to valsartan and hydrochlorothiazide tablet, if oliguria or hypotension occurs, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. hydrochlorothiazide thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. it accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. since they do not prevent or alter the course of eph (edema, proteinuria, hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. the use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided. data animal data valsartan plus hydrochlorothiazide there was no evidence of teratogenicity in mice, rats, or rabbits treated orally with valsartan at doses of up to 600, 100, and 10 mg/kg/day [9, 3.5 and 0.5 times the maximum recommended human dose (mrhd)], respectively, in combination with hydrochlorothiazide at doses up to 188, 31, and 3 mg/kg/day (38, 13 and 2 times the mrhd). fetotoxicity was observed in association with maternal toxicity in rats at valsartan/hydrochlorothiazide doses of ≥ 200/63 mg/kg/day and in rabbits at valsartan/hydrochlorothiazide doses of 10/3 mg/kg/day. evidence of fetotoxicity in rats consisted of decreased fetal weight and fetal variations of sternebrae, vertebrae, ribs, and/or renal papillae. evidence of fetotoxicity in rabbits included increased numbers of late resorptions with resultant increases in total resorptions, post-implantation losses, and decreased number of live fetuses. risk summary there is limited information regarding the presence of  valsartan and hydrochlorothiazide tablet in human milk, the effects on the breastfed infant, or the effects on milk production. valsartan is present in rat milk. hydrochlorothiazide is present in human breast milk. because of the potential for serious adverse reactions in breastfed infants, advise a nursing woman that breastfeeding is not recommended during treatment with valsartan and hydrochlorothiazide tablet. data valsartan was detected in the milk of lactating rats 15 minutes after oral administration of a 3 mg/kg dose. safety and effectiveness of valsartan and hydrochlorothiazide tablet in pediatric patients have not been established. in the controlled clinical trials of valsartan and hydrochlorothiazide tablets, 764 (17.5%) patients treated with valsartan-hydrochlorothiazide were ≥ 65 years and 118 (2.7%) were ≥ 75 years. no overall difference in the efficacy or safety of valsartan-hydrochlorothiazide was observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. safety and effectiveness of valsartan and hydrochlorothiazide tablets in patients with severe renal impairment (crcl ≤ 30 ml/min) have not been established. no dose adjustment is required in patients with mild (crcl 60 to 90 ml/min) or moderate (crcl 30 to 60ml/min) renal impairment. valsartan no dose adjustment is necessary for patients with mild-to-moderate liver disease. no dosing recommendations can be provided for patients with severe liver disease. hydrochlorothiazide minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

澳大利亚 - 英文 - Department of Health (Therapeutic Goods Administration)

vantive pty ltd - 41049 - nephrology information system application software - adequest is a web-based peritoneal dialysis kinetic modeling application used to assist healthcare professionals in measuring patient peritoneal membrane transport characteristics and in the modelling of solute clearances, fluid removal and carbohydrate absorption based on transport characteristics and treatment parameters provided by the healthcare professionals. adequest cannot determine whether a patient is receiving adequet therapy and is not designed to be a tool to teach healthcare professional how to perform or prescribe pd. adequest will not autofill or directly input any therapy models into the pd instrucmentations.

美国 - 英文 - NLM (National Library of Medicine)

a-s medication solutions - valsartan (unii: 80m03yxj7i) (valsartan - unii:80m03yxj7i), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - valsartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension, to lower blood pressure. lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. these benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes, including hydrochlorothiazide and the angiotensin ii receptor blocker (arb) class to which valsartan principally belongs. there are no controlled trials demonstrating risk reduction with valsartan and hydrochlorothiazide tablets. control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. many patients will require more than 1 drug to achieve blood pressure goals. for specific advice on goals and management, see published guidelines, such as those of the national high blood pressure education program’s joint national committee on prevention, detection, evaluation, and treatment of high blood pressure (jnc). numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. the largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality have also been seen regularly. elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmhg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (e.g., patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). these considerations may guide selection of therapy. add-on therapy valsartan and hydrochlorothiazide tablets may be used in patients whose blood pressure is not adequately controlled on monotherapy. replacement therapy valsartan and hydrochlorothiazide tablets may be substituted for the titrated components.  initial therapy valsartan and hydrochlorothiazide tablets may be used as initial therapy in patients who are likely to need multiple drugs to achieve blood pressure goals. the choice of valsartan and hydrochlorothiazide tablets as initial therapy for hypertension should be based on an assessment of potential benefits and risks. patients with stage 2 hypertension are at a relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and should be shaped by considerations such as baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared to monotherapy. individual blood pressure goals may vary based upon the patient's risk. data from the high dose multifactorial trial [see clinical studies (14.1)] provides estimates of the probability of reaching a target blood pressure with valsartan and hydrochlorothiazide tablets compared to valsartan or hydrochlorothiazide monotherapy. the figures below provide estimates of the likelihood of achieving systolic or diastolic blood pressure control with valsartan and hydrochlorothiazide tablets 320/25 mg, based upon baseline systolic or diastolic blood pressure. the curve of each treatment group was estimated by logistic regression modeling. the estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. figure 1: probability of achieving systolic blood pressure <140 mmhg at week 8 figure 2: probability of achieving diastolic blood pressure <90 mmhg at week 8 figure 3: probability of achieving systolic blood pressure <130 mmhg at week 8 figure 4: probability of achieving diastolic blood pressure <80 mmhg at week 8 for example, a patient with a baseline blood pressure of 160/100 mmhg has about a 41% likelihood of achieving a goal of < 140 mmhg (systolic) and 60% likelihood of achieving < 90 mmhg (diastolic) on valsartan alone and the likelihood of achieving these goals on hctz alone is about 50% (systolic) or 57% (diastolic). the likelihood of achieving these goals on valsartan and hydrochlorothiazide tablets rises to about 84% (systolic) or 80% (diastolic). the likelihood of achieving these goals on placebo is about 23% (systolic) or 36% (diastolic). valsartan and hydrochlorothiazide tablets is contraindicated in patients who are hypersensitive to any component of this product. because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs.   do not coadminister aliskiren with valsartan and hydrochlorothiazide tablets in patients with diabetes [see drug interactions (7)]. risk summary valsartan and hydrochlorothiazide tablet can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. published reports include cases of anhydramnios and oligohydramnios in pregnant women treated with valsartan (see clinical considerations).   when pregnancy is detected discontinue valsartan and hydrochlorothiazide tablet as soon as possible.   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 2-4% and 15-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk hypertension in pregnancy increases the maternal risk for pre-eclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and post-partum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions valsartan oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of gestation. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. if oligohydramnios is observed, consider alternative drug treatment. closely observe neonates with histories of in utero exposure to valsartan and hydrochlorothiazide tablet for hypotension, oliguria, and hyperkalemia. in neonates with a history of in utero exposure to valsartan and hydrochlorothiazide tablet, if oliguria or hypotension occurs, support blood pressure and renal perfusion. exchange transfusions or dialysis may be required as a means of reversing hypotension and replacing renal function. hydrochlorothiazide thiazides can cross the placenta, and concentrations reached in the umbilical vein approach those in the maternal plasma. hydrochlorothiazide, like other diuretics, can cause placental hypoperfusion. it accumulates in the amniotic fluid, with reported concentrations up to 19 times higher than in umbilical vein plasma. use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice or thrombocytopenia. since they do not prevent or alter the course of eph (edema, proteinuria, hypertension) gestosis (pre-eclampsia), these drugs should not be used to treat hypertension in pregnant women. the use of hydrochlorothiazide for other indications (e.g., heart disease) in pregnancy should be avoided. data animal data valsartan plus hydrochlorothiazide there was no evidence of teratogenicity in mice, rats, or rabbits treated orally with valsartan at doses of up to 600, 100, and 10 mg/kg/day [9, 3.5 and 0.5 times the maximum recommended human dose (mrhd)], respectively, in combination with hydrochlorothiazide at doses up to 188, 31, and 3 mg/kg/day (38, 13 and 2 times the mrhd). fetotoxicity was observed in association with maternal toxicity in rats at valsartan/hydrochlorothiazide doses of ≥ 200/63 mg/kg/day and in rabbits at valsartan/hydrochlorothiazide doses of 10/3 mg/kg/day. evidence of fetotoxicity in rats consisted of decreased fetal weight and fetal variations of sternebrae, vertebrae, ribs, and/or renal papillae. evidence of fetotoxicity in rabbits included increased numbers of late resorptions with resultant increases in total resorptions, post-implantation losses, and decreased number of live fetuses. risk summary there is limited information regarding the presence of  valsartan and hydrochlorothiazide tablet in human milk, the effects on the breastfed infant, or the effects on milk production. valsartan is present in rat milk. hydrochlorothiazide is present in human breast milk. because of the potential for serious adverse reactions in breastfed infants, advise a nursing woman that breastfeeding is not recommended during treatment with valsartan and hydrochlorothiazide tablet. data valsartan was detected in the milk of lactating rats 15 minutes after oral administration of a 3 mg/kg dose. safety and effectiveness of valsartan and hydrochlorothiazide tablet in pediatric patients have not been established. in the controlled clinical trials of valsartan and hydrochlorothiazide tablets, 764 (17.5%) patients treated with valsartan-hydrochlorothiazide were ≥ 65 years and 118 (2.7%) were ≥ 75 years. no overall difference in the efficacy or safety of valsartan-hydrochlorothiazide was observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. safety and effectiveness of valsartan and hydrochlorothiazide tablets in patients with severe renal impairment (crcl ≤ 30 ml/min) have not been established. no dose adjustment is required in patients with mild (crcl 60 to 90 ml/min) or moderate (crcl 30 to 60ml/min) renal impairment. valsartan no dose adjustment is necessary for patients with mild-to-moderate liver disease. no dosing recommendations can be provided for patients with severe liver disease. hydrochlorothiazide minor alterations of fluid and electrolyte balance may precipitate hepatic coma in patients with impaired hepatic function or progressive liver disease.

美国 - 英文 - NLM (National Library of Medicine)

remedyrepack inc. - irbesartan (unii: j0e2756z7n) (irbesartan - unii:j0e2756z7n), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - irbesartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension. irbesartan and hydrochlorothiazide tablets may be used in patients whose blood pressure is not adequately controlled on monotherapy. irbesartan and hydrochlorothiazide tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. - the choice of irbesartan and hydrochlorothiazide tablets as initial therapy for hypertension should be based on an assessment of potential benefits and risks. patients with stage 2 (moderate or severe) hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and may be shaped by considerations such as the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy. data from studies v and vi [see clinical studies (14.2) ] provide estimates of the probability of reaching a blood pressure goal with irbesartan and hydrochlorothiazide tablets compared to irbesartan or hydrochlorothiazide (hctz) monotherapy. the relationship between baseline blood pressure and achievement of a sesbp <140 or <130 mmhg or sedbp <90 or <80 mmhg in patients treated with irbesartan and hydrochlorothiazide tablets compared to patients treated with irbesartan or hctz monotherapy are shown in figures 1a through 2b. the above graphs provide a rough approximation of the likelihood of reaching a targeted blood pressure goal (e.g., week 8 sitting systolic blood pressure ≤140 mmhg) for the treatment groups. the curve of each treatment group in each study was estimated by logistic regression modeling from all available data of that treatment group. the estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. for example, a patient with a blood pressure of 180/105 mmhg has about a 25% likelihood of achieving a goal of <140 mmhg (systolic) and 50% likelihood of achieving <90 mmhg (diastolic) on irbesartan alone (and lower still likelihoods on hctz alone). the likelihood of achieving these goals on irbesartan and hydrochlorothiazide tablets rise to about 40% (systolic) or 70% (diastolic). - irbesartan and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to any component of this product. - because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. - do not coadminister aliskiren with irbesartan and hydrochlorothiazide tablets in patients with diabetes [see drug interactions (7) ]. irbesartan and hydrochlorothiazide tablets can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations]. most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue irbesartan and hydrochlorothiazide tablets as soon as possible. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes regardless of drug exposure. 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. clinical considerations disease-associated maternal and/or embryo-fetal risk hypertension in pregnancy increases the maternal risk for preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and postpartum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to irbesartan and hydrochlorothiazide tablets for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment. in neonates with a history of in utero exposure to irbesartan and hydrochlorothiazide tablets, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults [see warnings and precautions (5.1)]. data animal data irbesartan crosses the placenta in rats and rabbits. in female rats given irbesartan prior to mating through gestation and lactation at oral doses of 50, 180, or 650 mg/kg/day (1.6 to 21.1 times the maximum recommended human dose (mrhd) based on body surface area), fetuses examined on gestation day 20 showed increased incidences of hydroureter and renal pelvic cavitation and/or absence of renal papilla in all irbesartan-treated groups. subcutaneous edema also occurred in fetuses at maternal doses ≥180 mg/kg/day (5.8 times the mrhd). these anomalies occurred when female rats received irbesartan from prior to mating through day 20 of gestation but were not observed in pups postnatally in the same study, or when irbesartan was given to pregnant rats only during organogenesis (gestation day 6 through gestation day 15) at oral doses from 50 to 450 mg/kg/day (up to 14.6 times the mrhd). in addition, no adverse effects on kidney development were observed in pups from dams given irbesartan from gestation day 15 through lactation day 24 at doses of 50, 180, or 650 mg/kg/day (up to 21.1 times the mrhd). the observed effects are believed to be late gestational effects of the drug. pregnant rabbits given oral doses of irbesartan of 30 mg/kg/day (1.9 times the mrhd based on body surface area) experienced a high rate of maternal mortality and abortion. surviving females had a slight increase in early resorptions and a corresponding decrease in live fetuses. radioactivity was present in the rat and rabbit fetuses during late gestation following oral doses of radiolabeled irbesartan. when pregnant mice and rats were given hydrochlorothiazide at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the mrhd) during their respective periods of major organogenesis, there was no evidence of fetal harm. a development toxicity study was performed in rats with doses of 50/50 mg/kg/day and 150/150 mg/kg/day irbesartan and hydrochlorothiazide. although the high dose combination appeared to be more toxic to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. there are no available data on the presence of irbesartan in human milk, effects on milk production, or the breastfed infant. irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats. thiazides appear in human milk [see clinical pharmacology (12.3)]. because of the potential for adverse effects on the nursing infant, the use of irbesartan and hydrochlorothiazide tablets in breastfeeding women is not recommended. safety and effectiveness in pediatric patients have not been established. of 1694 patients receiving irbesartan and hydrochlorothiazide tablets in controlled clinical studies of hypertension, 264 (15.6%) were 65 years and over, while 45 (2.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. [see clinical pharmacology (12.3) and clinical studies (14) .]

美国 - 英文 - NLM (National Library of Medicine)

preferred pharmaceuticals inc. - alendronate sodium (unii: 2uy4m2u3ra) (alendronic acid - unii:x1j18r4w8p) - alendronate sodium tablets, usp are indicated for the treatment of osteoporosis in postmenopausal women. in postmenopausal women, alendronate sodium tablets, usp increases bone mass and reduces the incidence of fractures, including those of the hip and spine (vertebral compression fractures). [see clinical studies (14.1).] alendronate sodium tablets, usp are indicated for the prevention of postmenopausal osteoporosis [see clinical studies (14.2)]. alendronate sodium tablets, usp are indicated for treatment to increase bone mass in men with osteoporosis [see clinical studies (14.3)]. alendronate sodium tablets, usp are indicated for the treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low bone mineral density [see clinical studies (14.4)]. alendronate sodium tablets, usp are indicated for the treatment of paget's disease of bone in men and women. treatment is indicated in patients with paget's disease of bone who have alkaline phosphatase at least two times the upper limit of normal, or those who are symptomatic, or those at risk for future complications from their disease. [see clinical studies (14.5).] the optimal duration of use has not been determined. the safety and effectiveness of alendronate sodium for the treatment of osteoporosis are based on clinical data of four years duration. all patients on bisphosphonate therapy should have the need for continued therapy re-evaluated on a periodic basis. patients at low-risk for fracture should be considered for drug discontinuation after 3 to 5 years of use. patients who discontinue therapy should have their risk for fracture re-evaluated periodically. alendronate sodium tablets are contraindicated in patients with the following conditions: risk summary available data on the use of alendronate sodium in pregnant women are insufficient to inform a drug-associated risk of adverse maternal or fetal outcomes. discontinue alendronate sodium when pregnancy is recognized. in animal reproduction studies, daily oral administration of alendronate to rats from before mating through the end of gestation or lactation showed decreased postimplantation survival and decreased pup body weight gain starting at doses equivalent to less than half of the highest recommended 40 mg clinical daily dose (based on body surface area, mg/m2 ). oral administration of alendronate to rats during organogenesis resulted in reduced fetal ossification starting at doses 3 times the 40 mg clinical daily dose. no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at doses equivalent to approximately 10 times the 40 mg clinical daily dose. delayed or failed delivery of offspring, protracted parturition, and late pregnancy maternal and fetal deaths due to maternal hypocalcemia occurred in rats at oral doses as low as one tenth the 40 mg clinical daily dose (see data) . bisphosphonates are incorporated into the bone matrix, from which they are gradually released over a period of years. the amount of bisphosphonate incorporated into adult bone and available for release into the systemic circulation is directly related to the dose and duration of bisphosphonate use. consequently, based on the mechanism of action of bisphosphonates, there is a potential risk of fetal harm, predominantly skeletal, if a woman becomes pregnant after completing a course of bisphosphonate therapy. the impact of variables such as time between cessation of bisphosphonate therapy to conception, the particular bisphosphonate used, and the route of administration (intravenous versus oral) on the risk has not been studied. the estimated background risk of major birth defects and miscarriage for the indicated population(s) is unknown. all pregnancies have a background risk of birth defects, loss, or other adverse outcomes. in the u.s. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. data animal data reproduction studies in rats dosed orally from before mating to the end of gestation or lactation showed decreased postimplantation survival starting at 2 mg/kg/day and decreased body weight gain starting at 1 mg/kg/day, doses equivalent to less than half the 40 mg clinical daily dose based on body surface area, mg/m2 . incidence of incomplete fetal ossification in vertebral, skull, and sternebral bones were increased in rats dosed orally during organogenesis starting at 10 mg/kg/day (approximately 3 times the 40 mg clinical daily dose). no similar fetal effects were observed in pregnant rabbits dosed orally during organogenesis at up to 35 mg/kg/day (equivalent to approximately 10 times the 40 mg clinical daily dose). both total and ionized calcium decreased in pregnant rats dosed orally with 15 mg/kg/day alendronate (approximately 4 times the 40 mg clinical daily dose) resulting in delays and failures of delivery. protracted parturition due to maternal hypocalcemia was observed when rats were treated from before mating through gestation starting at 0.5 mg/kg/day (approximately one tenth the 40 mg clinical daily dose). maternotoxicity (late pregnancy deaths) also occurred in the female rats treated orally with 15 mg/kg/day (approximately 4 times the 40 mg clinical daily dose) for varying gestational time periods. these maternal deaths were lessened but not eliminated by cessation of treatment. calcium supplementation in the drinking water or by subcutaneous minipump to rats dosed orally with 15 mg/kg/day alendronate could not ameliorate the hypocalcemia or prevent the dystocia-related maternal and neonatal deaths. however, intravenous calcium supplementation prevented maternal, but not neonatal deaths. risk summary it is not known whether alendronate is present in human breast milk, affects human milk production, or has effects on the breastfed infant. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for alendronate sodium and any potential adverse effects on the breastfed child from alendronate sodium or from the underlying maternal condition. alendronate sodium is not indicated for use in pediatric patients. the safety and efficacy of alendronate sodium were examined in a randomized, double-blind, placebo-controlled two-year study of 139 pediatric patients, aged 4-18 years, with severe osteogenesis imperfecta (oi). one-hundred-and-nine patients were randomized to 5 mg alendronate sodium daily (weight less than 40 kg) or 10 mg alendronate sodium daily (weight greater than or equal to 40 kg) and 30 patients to placebo. the mean baseline lumbar spine bmd z-score of the patients was -4.5. the mean change in lumbar spine bmd z-score from baseline to month 24 was 1.3 in the alendronate sodium-treated patients and 0.1 in the placebo-treated patients. treatment with alendronate sodium did not reduce the risk of fracture. sixteen percent of the alendronate sodium patients who sustained a radiologically-confirmed fracture by month 12 of the study had delayed fracture healing (callus remodeling) or fracture non-union when assessed radiographically at month 24 compared with 9% of the placebo-treated patients. in alendronate sodium-treated patients, bone histomorphometry data obtained at month 24 demonstrated decreased bone turnover and delayed mineralization time; however, there were no mineralization defects. there were no statistically significant differences between the alendronate sodium and placebo groups in reduction of bone pain. the oral bioavailability in children was similar to that observed in adults. the overall safety profile of alendronate sodium in osteogenesis imperfecta patients treated for up to 24 months was generally similar to that of adults with osteoporosis treated with alendronate sodium. however, there was an increased occurrence of vomiting in osteogenesis imperfecta patients treated with alendronate sodium compared to placebo. during the 24-month treatment period, vomiting was observed in 32 of 109 (29.4%) patients treated with alendronate sodium and 3 of 30 (10%) patients treated with placebo. in a pharmacokinetic study, 6 of 24 pediatric osteogenesis imperfecta patients who received a single oral dose of alendronate sodium 35 or 70 mg developed fever, flu-like symptoms, and/or mild lymphocytopenia within 24 to 48 hours after administration. these events, lasting no more than 2 to 3 days and responding to acetaminophen, are consistent with an acute-phase response that has been reported in patients receiving bisphosphonates, including alendronate sodium. [see adverse reactions (6.2).] of the patients receiving alendronate sodium in the fracture intervention trial (fit), 71% (n=2302) were greater than or equal to 65 years of age and 17% (n=550) were greater than or equal to 75 years of age. of the patients receiving alendronate sodium in the united states and multinational osteoporosis treatment studies in women, osteoporosis studies in men, glucocorticoid-induced osteoporosis studies, and paget's disease studies [see clinical studies (14.1), (14.3), (14.4), (14.5)], 45%, 54%, 37%, and 70%, respectively, were 65 years of age or over. no overall differences in efficacy or safety were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. alendronate sodium is not recommended for patients with creatinine clearance less than 35 ml/min. no dosage adjustment is necessary in patients with creatinine clearance values between 35-60 ml/min [see clinical pharmacology (12.3)] . as there is evidence that alendronate is not metabolized or excreted in the bile, no studies were conducted in patients with hepatic impairment. no dosage adjustment is necessary [see clinical pharmacology (12.3)] .

美国 - 英文 - NLM (National Library of Medicine)

ulab - glycerin (unii: pdc6a3c0ox) (glycerin - unii:pdc6a3c0ox) - purpose: skin firming and remodeling indications & usage: use one to three times a week

美国 - 英文 - NLM (National Library of Medicine)

remedyrepack inc. - irbesartan (unii: j0e2756z7n) (irbesartan - unii:j0e2756z7n), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - irbesartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension. irbesartan and hydrochlorothiazide tablets may be used in patients whose blood pressure is not adequately controlled on monotherapy. irbesartan and hydrochlorothiazide tablets may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. the choice of irbesartan and hydrochlorothiazide tablets as initial therapy for hypertension should be based on an assessment of potential benefits and risks. patients with stage 2 (moderate or severe) hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and may be shaped by considerations such as the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy. data from studies v and vi [ see clinical studies ( 14.2) ] provide estimates of the probability of reaching a blood pressure goal with irbesartan and hydrochlorothiazide tablets compared to irbesartan or hydrochlorothiazide (hctz) monotherapy. the relationship between baseline blood pressure and achievement of a sesbp <140 or <130 mmhg or sedbp <90 or <80 mmhg in patients treated with irbesartan and hydrochlorothiazide tablets compared to patients treated with irbesartan or hctz monotherapy are shown in figures 1a through 2b.  figure 1a: probability of achieving sbp <140 mmhg in patients from initial therapy studies v (week 8) and vi (week 7) * figure 1b: probability of achieving sbp <130 mmhg in patients from initial therapy studies v (week 8) and vi (week 7) * figure 2a: probability of achieving dbp <90 mmhg in patients from initial therapy studies v (week 8) and vi (week 7) * figure 2b: probability of achieving dbp <80 mmhg in patients from initial therapy studies v (week 8) and vi (week 7) * * for all probability curves, patients without blood pressure measurements at week 7 (study vi) and week 8 (study v) were counted as not reaching goal (intent-to-treat analysis). the above graphs provide a rough approximation of the likelihood of reaching a targeted blood pressure goal (e.g., week 8 sitting systolic blood pressure ≤140 mmhg) for the treatment groups. the curve of each treatment group in each study was estimated by logistic regression modeling from all available data of that treatment group. the estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. for example, a patient with a blood pressure of 180/105 mmhg has about a 25% likelihood of achieving a goal of <140 mmhg (systolic) and 50% likelihood of achieving <90 mmhg (diastolic) on irbesartan alone (and lower still likelihoods on hctz alone). the likelihood of achieving these goals on irbesartan and hydrochlorothiazide tablets rises to about 40% (systolic) or 70% (diastolic). - irbesartan and hydrochlorothiazide tablets are contraindicated in patients who are hypersensitive to any component of this product. - because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. - do not coadminister aliskiren with irbesartan and hydrochlorothiazide tablets in patients with diabetes [ see drug interactions ( 7) ]. risk summary irbesartan and hydrochlorothiazide can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [ see clinical considerations ] . most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue irbesartan and hydrochlorothiazide as soon as possible. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes regardless of drug exposure. 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. clinical considerations disease-associated maternal and/or embryo-fetal risk hypertension in pregnancy increases the maternal risk for preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and postpartum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to irbesartan and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment. in neonates with a history of in utero exposure to irbesartan and hydrochlorothiazide, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function.   thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults [ see warnings and precautions ( 5.1) ] . data animal data irbesartan crosses the placenta in rats and rabbits. in female rats given irbesartan prior to mating through gestation and lactation at oral doses of 50, 180, or 650 mg/kg/day (1.6 to 21.1 times the maximum recommended human dose (mrhd) based on body surface area), fetuses examined on gestation day 20 showed increased incidences of hydroureter and renal pelvic cavitation and/or absence of renal papilla in all irbesartan-treated groups. subcutaneous edema also occurred in fetuses at maternal doses ≥180 mg/kg/day (5.8 times the mrhd). these anomalies occurred when female rats received irbesartan from prior to mating through day 20 of gestation but were not observed in pups postnatally in the same study, or when irbesartan was given to pregnant rats only during organogenesis (gestation day 6 through gestation day 15) at oral doses from 50 to 450 mg/kg/day (up to 14.6 times the mrhd). in addition, no adverse effects on kidney development were observed in pups from dams given irbesartan from gestation day 15 through lactation day 24 at doses of 50, 180, or 650 mg/kg/day (up to 21.1 times the mrhd). the observed effects are believed to be late gestational effects of the drug. pregnant rabbits given oral doses of irbesartan of 30 mg/kg/day (1.9 times the mrhd based on body surface area) experienced a high rate of maternal mortality and abortion. surviving females had a slight increase in early resorptions and a corresponding decrease in live fetuses. radioactivity was present in the rat and rabbit fetuses during late gestation following oral doses of radiolabeled irbesartan. when pregnant mice and rats were given hydrochlorothiazide at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the mrhd) during their respective periods of major organogenesis, there was no evidence of fetal harm. a development toxicity study was performed in rats with doses of 50/50 mg/kg/day and 150/150 mg/kg/day irbesartan and hydrochlorothiazide. although the high dose combination appeared to be more toxic to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. there are no available data on the presence of irbesartan in human milk, effects on milk production, or the breastfed infant. irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats. thiazides appear in human milk [ see clinical pharmacology ( 12.3) ] . because of the potential for adverse effects on the nursing infant, the use of irbesartan and hydrochlorothiazide in breastfeeding women is not recommended. safety and effectiveness in pediatric patients have not been established. of 1694 patients receiving irbesartan and hydrochlorothiazide in controlled clinical studies of hypertension, 264 (15.6%) were 65 years and over, while 45 (2.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out [ see clinical pharmacology ( 12.3) and clinical studies ( 14) ].

美国 - 英文 - NLM (National Library of Medicine)

winthrop u.s, a business of sanofi-aventis u.s. llc - irbesartan (unii: j0e2756z7n) (irbesartan - unii:j0e2756z7n), hydrochlorothiazide (unii: 0j48lph2th) (hydrochlorothiazide - unii:0j48lph2th) - irbesartan and hydrochlorothiazide tablets are indicated for the treatment of hypertension. irbesartan and hydrochlorothiazide may be used in patients whose blood pressure is not adequately controlled on monotherapy. irbesartan and hydrochlorothiazide may also be used as initial therapy in patients who are likely to need multiple drugs to achieve their blood pressure goals. the choice of irbesartan and hydrochlorothiazide as initial therapy for hypertension should be based on an assessment of potential benefits and risks. patients with stage 2 (moderate or severe) hypertension are at relatively high risk for cardiovascular events (such as strokes, heart attacks, and heart failure), kidney failure, and vision problems, so prompt treatment is clinically relevant. the decision to use a combination as initial therapy should be individualized and may be shaped by considerations such as the baseline blood pressure, the target goal, and the incremental likelihood of achieving goal with a combination compared with monotherapy. data from studies v and vi [see clinical studies (14.2)] provide estimates of the probability of reaching a blood pressure goal with irbesartan and hydrochlorothiazide compared to irbesartan or hydrochlorothiazide (hctz) monotherapy. the relationship between baseline blood pressure and achievement of a sesbp <140 or <130 mmhg or sedbp <90 or <80 mmhg in patients treated with irbesartan and hydrochlorothiazide compared to patients treated with irbesartan or hctz monotherapy are shown in figures 1a through 2b. the above graphs provide a rough approximation of the likelihood of reaching a targeted blood pressure goal (e.g., week 8 sitting systolic blood pressure ≤140 mmhg) for the treatment groups. the curve of each treatment group in each study was estimated by logistic regression modeling from all available data of that treatment group. the estimated likelihood at the right tail of each curve is less reliable due to small numbers of subjects with high baseline blood pressures. for example, a patient with a blood pressure of 180/105 mmhg has about a 25% likelihood of achieving a goal of <140 mmhg (systolic) and 50% likelihood of achieving <90 mmhg (diastolic) on irbesartan alone (and lower still likelihoods on hctz alone). the likelihood of achieving these goals on irbesartan and hydrochlorothiazide rises to about 40% (systolic) or 70% (diastolic). - irbesartan and hydrochlorothiazide is contraindicated in patients who are hypersensitive to any component of this product. - because of the hydrochlorothiazide component, this product is contraindicated in patients with anuria or hypersensitivity to other sulfonamide-derived drugs. - do not coadminister aliskiren with irbesartan and hydrochlorothiazide in patients with diabetes [see drug interactions (7)] . risk summary irbesartan and hydrochlorothiazide can cause fetal harm when administered to a pregnant woman. use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death [see clinical considerations] . most epidemiologic studies examining fetal abnormalities after exposure to antihypertensive use in the first trimester have not distinguished drugs affecting the renin-angiotensin system from other antihypertensive agents. when pregnancy is detected, discontinue irbesartan and hydrochlorothiazide as soon as possible. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes regardless of drug exposure. 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. clinical considerations disease-associated maternal and/or embryo-fetal risk hypertension in pregnancy increases the maternal risk for preeclampsia, gestational diabetes, premature delivery, and delivery complications (e.g., need for cesarean section and postpartum hemorrhage). hypertension increases the fetal risk for intrauterine growth restriction and intrauterine death. pregnant women with hypertension should be carefully monitored and managed accordingly. fetal/neonatal adverse reactions oligohydramnios in pregnant women who use drugs affecting the renin-angiotensin system in the second and third trimesters of pregnancy can result in the following: reduced fetal renal function leading to anuria and renal failure, fetal lung hypoplasia, skeletal deformations, including skull hypoplasia, hypotension, and death. perform serial ultrasound examinations to assess the intra-amniotic environment. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to irbesartan and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia and other symptoms of renal impairment. in neonates with a history of in utero exposure to irbesartan and hydrochlorothiazide, if oliguria or hypotension occurs, direct attention toward support of blood pressure and renal perfusion. exchange transfusion or dialysis may be required as means of reversing hypotension and/or substituting for disordered renal function. thiazides cross the placenta, and use of thiazides during pregnancy is associated with a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults [see warnings and precautions (5.1)] . data animal data irbesartan crosses the placenta in rats and rabbits. in female rats given irbesartan prior to mating through gestation and lactation at oral doses of 50, 180, or 650 mg/kg/day (1.6 to 21.1 times the maximum recommended human dose (mrhd) based on body surface area), fetuses examined on gestation day 20 showed increased incidences of hydroureter and renal pelvic cavitation and/or absence of renal papilla in all irbesartan-treated groups. subcutaneous edema also occurred in fetuses at maternal doses ≥180 mg/kg/day (5.8 times the mrhd). these anomalies occurred when female rats received irbesartan from prior to mating through day 20 of gestation but were not observed in pups postnatally in the same study, or when irbesartan was given to pregnant rats only during organogenesis (gestation day 6 through gestation day 15) at oral doses from 50 to 450 mg/kg/day (up to 14.6 times the mrhd). in addition, no adverse effects on kidney development were observed in pups from dams given irbesartan from gestation day 15 through lactation day 24 at doses of 50, 180, or 650 mg/kg/day (up to 21.1 times the mrhd). the observed effects are believed to be late gestational effects of the drug. pregnant rabbits given oral doses of irbesartan of 30 mg/kg/day (1.9 times the mrhd based on body surface area) experienced a high rate of maternal mortality and abortion. surviving females had a slight increase in early resorptions and a corresponding decrease in live fetuses. radioactivity was present in the rat and rabbit fetuses during late gestation following oral doses of radiolabeled irbesartan. when pregnant mice and rats were given hydrochlorothiazide at doses up to 3000 and 1000 mg/kg/day, respectively (about 600 and 400 times the mrhd) during their respective periods of major organogenesis, there was no evidence of fetal harm. a development toxicity study was performed in rats with doses of 50/50 mg/kg/day and 150/150 mg/kg/day irbesartan and hydrochlorothiazide. although the high dose combination appeared to be more toxic to the dams than either drug alone, there did not appear to be an increase in toxicity to the developing embryos. there are no available data on the presence of irbesartan in human milk, effects on milk production, or the breastfed infant. irbesartan or some metabolite of irbesartan is secreted in the milk of lactating rats. thiazides appear in human milk [see clinical pharmacology (12.3)] . because of the potential for adverse effects on the nursing infant, the use of irbesartan and hydrochlorothiazide in breastfeeding women is not recommended. safety and effectiveness in pediatric patients have not been established. of 1694 patients receiving irbesartan and hydrochlorothiazide in controlled clinical studies of hypertension, 264 (15.6%) were 65 years and over, while 45 (2.7%) were 75 years and over. no overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out. [see clinical pharmacology (12.3)and clinical studies (14).]

澳大利亚 - 英文 - Department of Health (Therapeutic Goods Administration)

emergo asia pacific pty ltd t/a emergo australia - 40872 - mri system, application program software - symri is a post-processing software medical device intended for use in visualization of the brain. symri analyzes input data from mr imaging systems. symri utilizes data from a multi-delay, multi-echo acquisition (mdme) to generate parametric maps of r1, r2 relaxation rates, and proton density (pd). symri can generate multiple image contrasts from the parametric maps. symri enables post-acquisition image contrast adjustment. symri is indicated for head imaging. symri is also intended for automatic labeling, visualization and volumetric quantifcation of segmentable brain tissues from a set of mr images. brain tissue volumes are determined based on modeling of parametric maps from mdme images. when interpreted by a trained physician, symri images can provide information useful in determining diagnosis. symri should always be used in combination with at least one other, conventional mr acquisition (e.g. t2w flair).