미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - rivaroxaban (unii: 9ndf7jz4m3) (rivaroxaban - unii:9ndf7jz4m3) - xarelto is indicated to reduce the risk of stroke and systemic embolism in adult patients with nonvalvular atrial fibrillation. there are limited data on the relative effectiveness of xarelto and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled [see clinical studies (14.1)]. xarelto is indicated for the treatment of deep vein thrombosis (dvt). xarelto is indicated for the treatment of pulmonary embolism (pe). xarelto is indicated for the reduction in the risk of recurrence of dvt and/or pe in adult patients at continued risk for recurrent dvt and/or pe after completion of initial treatment lasting at least 6 months. xarelto is indicated for the prophylaxis of dvt, which may lead to pe in adult patients undergoing knee or hip replacement surgery. xarelto is indicated for the prophylaxis of venous thromboembolism (vte) and vte related death during hospitalization and post hospital discharge in adult patients admitted for an acute medical illness who are at risk for thromboembolic complications due to moderate or severe restricted mobility and other risk factors for vte and not at high risk of bleeding [see warnings and precautions (5.2) and clinical studies (14.5)] . xarelto, in combination with aspirin, is indicated to reduce the risk of major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) in adult patients with coronary artery disease. xarelto, in combination with aspirin, is indicated to reduce the risk of major thrombotic vascular events (myocardial infarction, ischemic stroke, acute limb ischemia, and major amputation of a vascular etiology) in adult patients with pad, including patients who have recently undergone a lower extremity revascularization procedure due to symptomatic pad. xarelto is indicated for the treatment of venous thromboembolism (vte) and the reduction in the risk of recurrent vte in pediatric patients from birth to less than 18 years after at least 5 days of initial parenteral anticoagulant treatment. xarelto is indicated for thromboprophylaxis in pediatric patients aged 2 years and older with congenital heart disease who have undergone the fontan procedure. xarelto is contraindicated in patients with: - active pathological bleeding [see warnings and precautions (5.2)] - severe hypersensitivity reaction to xarelto (e.g., anaphylactic reactions) [see adverse reactions (6.2)] risk summary the limited available data on xarelto in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes. use xarelto with caution in pregnant patients because of the potential for pregnancy related hemorrhage and/or emergent delivery. the anticoagulant effect of xarelto cannot be reliably monitored with standard laboratory testing. consider the benefits and risks of xarelto for the mother and possible risks to the fetus when prescribing xarelto to a pregnant woman [see warnings and precautions (5.2, 5.7)] . adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. the estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. 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 pregnancy is a risk factor for venous thromboembolism and that risk is increased in women with inherited or acquired thrombophilias. pregnant women with thromboembolic disease have an increased risk of maternal complications including pre-eclampsia. maternal thromboembolic disease increases the risk for intrauterine growth restriction, placental abruption and early and late pregnancy loss. fetal/neonatal adverse reactions based on the pharmacologic activity of factor xa inhibitors and the potential to cross the placenta, bleeding may occur at any site in the fetus and/or neonate. labor or delivery all patients receiving anticoagulants, including pregnant women, are at risk for bleeding and this risk may be increased during labor or delivery [see warnings and precautions (5.7)]. the risk of bleeding should be balanced with the risk of thrombotic events when considering the use of xarelto in this setting. data human data there are no adequate or well-controlled studies of xarelto in pregnant women, and dosing for pregnant women has not been established. post-marketing experience is currently insufficient to determine a rivaroxaban-associated risk for major birth defects or miscarriage. in an in vitro placenta perfusion model, unbound rivaroxaban was rapidly transferred across the human placenta. animal data rivaroxaban crosses the placenta in animals. rivaroxaban increased fetal toxicity (increased resorptions, decreased number of live fetuses, and decreased fetal body weight) when pregnant rabbits were given oral doses of ≥10 mg/kg rivaroxaban during the period of organogenesis. this dose corresponds to about 4 times the human exposure of unbound drug, based on auc comparisons at the highest recommended human dose of 20 mg/day. fetal body weights decreased when pregnant rats were given oral doses of 120 mg/kg during the period of organogenesis. this dose corresponds to about 14 times the human exposure of unbound drug. in rats, peripartal maternal bleeding and maternal and fetal death occurred at the rivaroxaban dose of 40 mg/kg (about 6 times maximum human exposure of the unbound drug at the human dose of 20 mg/day). risk summary rivaroxaban has been detected in human milk. there are insufficient data to determine the effects of rivaroxaban on the breastfed child or on milk production. rivaroxaban and/or its metabolites were present in the milk of rats. the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for xarelto and any potential adverse effects on the breastfed infant from xarelto or from the underlying maternal condition (see data) . data animal data following a single oral administration of 3 mg/kg of radioactive [ 14 c]-rivaroxaban to lactating rats between day 8 to 10 postpartum, the concentration of total radioactivity was determined in milk samples collected up to 32 hours post-dose. the estimated amount of radioactivity excreted with milk within 32 hours after administration was 2.1% of the maternal dose. females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. the risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including xarelto should be assessed in females of reproductive potential and those with abnormal uterine bleeding. the safety and effectiveness of xarelto have been established in pediatric patients from birth to less than 18 years for the treatment of vte and the reduction in risk of recurrent vte. use of xarelto is supported in these age groups by evidence from adequate and well-controlled studies of xarelto in adults with additional pharmacokinetic, safety and efficacy data from a multicenter, prospective, open-label, active-controlled randomized study in 500 pediatric patients from birth to less than 18 years of age. xarelto was not studied and therefore dosing cannot be reliably determined or recommended in children less than 6 months who were less than 37 weeks of gestation at birth; had less than 10 days of oral feeding, or had a body weight of less than 2.6 kg [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14.8)] . the safety and effectiveness of xarelto have been established for use in pediatric patients aged 2 years and older with congenital heart disease who have undergone the fontan procedure. use of xarelto is supported in these age groups by evidence from adequate and well-controlled studies of xarelto in adults with additional data from a multicenter, prospective, open-label, active controlled study in 112 pediatric patients to evaluate the single- and multiple-dose pharmacokinetic properties of xarelto and the safety and efficacy of xarelto when used for thromboprophylaxis for 12 months in children with single ventricle physiology who had the fontan procedure [see dosage and administration (2.2), adverse reactions (6.1), clinical pharmacology (12.3) and clinical studies (14.9)] . clinical studies that evaluated safety, efficacy, pharmacokinetic and pharmacodynamic data support the use of xarelto 10 mg, 15 mg, and 20 mg tablets in pediatric patients. for the xarelto 2.5 mg tablets, there are no safety, efficacy, pharmacokinetic and pharmacodynamic data to support the use in pediatric patients. therefore, xarelto 2.5 mg tablets are not recommended for use in pediatric patients. although not all adverse reactions identified in the adult population have been observed in clinical trials of children and adolescent patients, the same warnings and precautions for adults should be considered for children and adolescents. of the total number of adult patients in clinical trials for the approved indications of xarelto (n=64,943 patients), 64 percent were 65 years and over, with 27 percent 75 years and over. in clinical trials the efficacy of xarelto in the elderly (65 years or older) was similar to that seen in patients younger than 65 years. both thrombotic and bleeding event rates were higher in these older patients [see clinical pharmacology (12.3) and clinical studies (14)] . in pharmacokinetic studies, compared to healthy adult subjects with normal creatinine clearance, rivaroxaban exposure increased by approximately 44 to 64% in adult subjects with renal impairment. increases in pharmacodynamic effects were also observed [see clinical pharmacology (12.3)] . nonvalvular atrial fibrillation patients with chronic kidney disease not on dialysis in the rocket af trial, patients with crcl 30 to 50 ml/min were administered xarelto 15 mg once daily resulting in serum concentrations of rivaroxaban and clinical outcomes similar to those in patients with better renal function administered xarelto 20 mg once daily. patients with crcl <30 ml/min were not studied, but administration of xarelto 15 mg once daily is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment [see clinical pharmacology (12.3)] . patients with end-stage renal disease on dialysis clinical efficacy and safety studies with xarelto did not enroll patients with end-stage renal disease (esrd) on dialysis. in patients with esrd maintained on intermittent hemodialysis, administration of xarelto 15 mg once daily will result in concentrations of rivaroxaban and pharmacodynamic activity similar to those observed in the rocket af study [see clinical pharmacology (12.2, 12.3)] . it is not known whether these concentrations will lead to similar stroke reduction and bleeding risk in patients with esrd on dialysis as was seen in rocket af. treatment of dvt and/or pe and reduction in the risk of recurrence of dvt and/or pe in the einstein trials, patients with crcl values <30 ml/min at screening were excluded from the studies, but administration of xarelto is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment (crcl 30 to <50 ml/min) [see clinical pharmacology (12.3)]. observe closely and promptly evaluate any signs or symptoms of blood loss in patients with crcl 15 to <30 ml/min. avoid the use of xarelto in patients with crcl <15 ml/min. prophylaxis of dvt following hip or knee replacement surgery the combined analysis of the record 1–3 clinical efficacy studies did not show an increase in bleeding risk for patients with crcl 30 to 50 ml/min and reported a possible increase in total venous thromboemboli in this population. in the record 1–3 trials, patients with crcl values <30 ml/min at screening were excluded from the studies, but administration of xarelto 10 mg once daily is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment (crcl 30 to <50 ml/min) [see clinical pharmacology (12.3)]. observe closely and promptly evaluate any signs or symptoms of blood loss in patients with crcl 15 to <30 ml/min. avoid the use of xarelto in patients with crcl <15 ml/min. prophylaxis of venous thromboembolism in acutely ill medical patients at risk for thromboembolic complications not at high risk of bleeding patients with crcl values <30 ml/min at screening were excluded from the magellan study. in patients with crcl <30 ml/min a dose of xarelto 10 mg once daily is expected to result in serum concentrations of rivaroxaban similar to those in patients with moderate renal impairment (crcl 30 to <50 ml/min) [see clinical pharmacology (12.3)] . observe closely and promptly evaluate any signs or symptoms of blood loss in patients with crcl 15 to <30 ml/min. avoid use of xarelto in patients with crcl <15 ml/min. reduction of risk of major cardiovascular events in patients with cad and reduction of risk of major thrombotic vascular events in patients with pad, including patients after recent lower extremity revascularization due to symptomatic pad patients with chronic kidney disease not on dialysis patients with a crcl <15 ml/min at screening were excluded from compass and voyager, and limited data are available for patients with a crcl of 15 to 30 ml/min. in patients with crcl <30 ml/min, a dose of 2.5 mg xarelto twice daily is expected to give an exposure similar to that in patients with moderate renal impairment (crcl 30 to <50 ml/min) [see clinical pharmacology (12.3)] , whose efficacy and safety outcomes were similar to those with preserved renal function. patients with end-stage renal disease on dialysis no clinical outcome data is available for the use of xarelto with aspirin in patients with esrd on dialysis since these patients were not enrolled in compass or voyager. in patients with esrd maintained on intermittent hemodialysis, administration of xarelto 2.5 mg twice daily will result in concentrations of rivaroxaban and pharmacodynamic activity similar to those observed in moderate renal impaired patients in the compass study [see clinical pharmacology (12.2, 12.3)] . it is not known whether these concentrations will lead to similar cv risk reduction and bleeding risk in patients with esrd on dialysis as was seen in compass. pediatric use no dosage adjustment is required in patients 1 year of age or older with mild renal impairment (egfr 50 to ≤ 80 ml/min/1.73 m 2 ). there are limited clinical data in pediatric patients 1 year or older with moderate or severe renal impairment (egfr <50 ml/min/1.73 m 2 ); therefore, avoid the use of xarelto in these patients. there are no clinical data in pediatric patients younger than 1 year with serum creatinine results above 97.5 th percentile; therefore, avoid the use of xarelto in these patients [see dosage and administration (2.2)] . in a pharmacokinetic study, compared to healthy adult subjects with normal liver function, auc increases of 127% were observed in adult subjects with moderate hepatic impairment (child-pugh b). the safety or pk of xarelto in patients with severe hepatic impairment (child-pugh c) has not been evaluated [see clinical pharmacology (12.3)] . avoid the use of xarelto in patients with moderate (child-pugh b) and severe (child-pugh c) hepatic impairment or with any hepatic disease associated with coagulopathy. no clinical data are available in pediatric patients with hepatic impairment. this instructions for use contains information on how to give a dose of xarelto oral suspension. read this instructions for use before giving xarelto and each time you get a refill. there may be new information. this leaflet does not take the place of talking with your doctor about your child's medical condition or treatment. important information: - xarelto suspension is for oral use only. - give xarelto to your child exactly as prescribed by your doctor. the adult caregiver should give the dose. if you have questions, contact your doctor or pharmacist for more information on giving a dose. - only use the oral dosing syringe provided with xarelto oral suspension. contact your doctor or pharmacist if the oral dosing syringe is missing, lost or damaged. storage information store xarelto oral suspension at room temperature between 68°f to 77°f (20°c to 25°c). do not freeze. store the bottle upright with the oral dosing syringes in the original carton. keep xarelto and all medicines out of reach of children. xarelto oral dosing syringe: xarelto bottle check "discard after" date on the xarelto bottle. if "discard after" date has passed, do not use and call your doctor or pharmacist. wash hands. wash your hands well with soap and warm water. shake bottle slowly for 10 seconds before each use. check xarelto oral suspension. if there are lumps or granules at the bottom of the bottle, shake the bottle slowly again for 10 seconds . find your dose line. you can use either side of the syringe to set your dose. if using ml side of syringe: top of the plunger should line up with the prescribed ml. if using color side of syringe: top of the plunger should line up with the prescribed ml dose line at the bottom of the color band. if your dose is more than 5 ml. you will need to use the same syringe more than one time. repeat steps 4 and 5 to complete your dose. ask your pharmacist if you are not sure. push plunger all the way in to remove air. insert oral dosing syringe into bottle adaptor. twist off the cap from the bottle. do not remove the bottle adaptor from the bottle. insert the syringe tip into the bottle adaptor. fill oral dosing syringe. turn the bottle upside down, as shown. pull the plunger to fill the oral dosing syringe slightly past your prescribed dose line to help remove any air bubbles. caution: make sure you have enough medicine for a full dose. do not take a partial dose. tap syringe to move air bubbles to the top. doing this helps set the correct dose. adjust to your prescribed dose. if using ml side of syringe: push plunger to align with the prescribed dose line. if using color side of syringe: push plunger to align with the prescribed ml dose line at the bottom of the color band. remove oral dosing syringe. place the bottle on a flat surface. remove the oral dosing syringe from the bottle. give the dose. place the oral dosing syringe gently into the child's mouth with the tip of the syringe pointing toward the cheek and slowly press the plunger. this allows the child to swallow naturally. make sure the child swallows the full dose. if your child vomits or spits out the medicine repeatedly, contact your child's doctor right away. close xarelto bottle and rinse oral dosing syringe. rinse the oral dosing syringe with tap water and let it air dry. disposing xarelto bottle and syringe - throw the xarelto bottle away in your household trash. - throw away any used oral dosing syringe with the opening of a new xarelto bottle. - do not pour xarelto suspension down the drain (for example: sink, toilet, shower or tub). - do not recycle the bottle. manufactured for: janssen pharmaceuticals, inc. titusville, nj 08560 licensed from: bayer healthcare ag 51368 leverkusen, germany for patent information: www.janssenpatents.com © 2021 janssen pharmaceutical companies this instructions for use has been approved by the u.s. food and drug administration. issued: 02/2023

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - canagliflozin (unii: 0sac974z85) (canagliflozin anhydrous - unii:6s49dgr869) - invokana (canagliflozin) is indicated: - as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. - to reduce the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease (cvd). - to reduce the risk of end-stage kidney disease (eskd), doubling of serum creatinine, cardiovascular (cv) death, and hospitalization for heart failure in adults with type 2 diabetes mellitus and diabetic nephropathy with albuminuria greater than 300 mg/day. limitations of use invokana is not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus [see warnings and precautions (5.1)] . invokana is not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m 2 . invokana is likely to be ineffective in this setting based upon its mechanism of action. invokana is contraindicated in patients with a serious hypersensitivity reaction to invokana, such as anaphylaxis or angioedema [see warnings and precautions (5.8)and adverse reactions (6.1, 6.2)] . risk summary based on animal data showing adverse renal effects, invokana is not recommended during the second and third trimesters of pregnancy. limited data with invokana in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal studies, adverse renal pelvic and tubule dilatations that were not reversible were observed in rats when canagliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy, at an exposure 0.5-times the 300 mg clinical dose, based on auc. the estimated background risk of major birth defects is 6–10% in women with pre-gestational diabetes with a hba 1c >7 and has been reported to be as high as 20–25% in women with a hba 1c >10. the estimated background risk of 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 2–4% and 15–20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. animal data canagliflozin dosed directly to juvenile rats from postnatal day (pnd) 21 until pnd 90 at doses of 4, 20, 65, or 100 mg/kg increased kidney weights and dose dependently increased the incidence and severity of renal pelvic and tubular dilatation at all doses tested. exposure at the lowest dose was greater than or equal to 0.5-times the 300 mg clinical dose, based on auc. these outcomes occurred with drug exposure during periods of renal development in rats that correspond to the late second and third trimester of human renal development. the renal pelvic dilatations observed in juvenile animals did not fully reverse within a 1-month recovery period. in embryo-fetal development studies in rats and rabbits, canagliflozin was administered for intervals coinciding with the first trimester period of organogenesis in humans. no developmental toxicities independent of maternal toxicity were observed when canagliflozin was administered at doses up to 100 mg/kg in pregnant rats and 160 mg/kg in pregnant rabbits during embryonic organogenesis or during a study in which maternal rats were dosed from gestation day (gd) 6 through pnd 21, yielding exposures up to approximately 19-times the 300 mg clinical dose, based on auc. risk summary there is no information regarding the presence of invokana in human milk, the effects on the breastfed infant, or the effects on milk production. canagliflozin is present in the milk of lactating rats [see data] . since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney. because of the potential for serious adverse reactions in a breastfed infant, advise women that use of invokana is not recommended while breastfeeding. data animal data radiolabeled canagliflozin administered to lactating rats on day 13 post-partum was present at a milk/plasma ratio of 1.40, indicating that canagliflozin and its metabolites are transferred into milk at a concentration comparable to that in plasma. juvenile rats directly exposed to canagliflozin showed a risk to the developing kidney (renal pelvic and tubular dilatations) during maturation. safety and effectiveness of invokana in pediatric patients under 18 years of age have not been established. in 13 clinical trials of invokana, 2,294 patients 65 years and older, and 351 patients 75 years and older were exposed to invokana [see clinical studies (14.1)] . patients 65 years and older had a higher incidence of adverse reactions related to reduced intravascular volume with invokana (such as hypotension, postural dizziness, orthostatic hypotension, syncope, and dehydration), particularly with the 300 mg daily dose, compared to younger patients; a more prominent increase in the incidence was seen in patients who were 75 years and older [see dosage and administration (2.1)and adverse reactions (6.1)]. smaller reductions in hba 1c with invokana relative to placebo were seen in older (65 years and older; -0.61% with invokana 100 mg and -0.74% with invokana 300 mg relative to placebo) compared to younger patients (-0.72% with invokana 100 mg and -0.87% with invokana 300 mg relative to placebo). the efficacy and safety of invokana for glycemic control were evaluated in a trial that included patients with moderate renal impairment (egfr 30 to less than 50 ml/min/1.73 m 2 ) [see clinical studies (14.1)] . these patients had less overall glycemic efficacy, and patients treated with 300 mg per day had increases in serum potassium, which were transient and similar by the end of study. patients with renal impairment using invokana for glycemic control may also be more likely to experience hypotension and may be at higher risk for acute kidney injury [see warnings and precautions (5.3)] . efficacy and safety studies with invokana did not enroll patients with eskd on dialysis or patients with an egfr less than 30 ml/min/1.73 m 2 [see clinical pharmacology (12.3)] . no dosage adjustment is necessary in patients with mild or moderate hepatic impairment. the use of invokana has not been studied in patients with severe hepatic impairment and is therefore not recommended [see clinical pharmacology (12.3)] .

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - empagliflozin (unii: hdc1r2m35u) (empagliflozin - unii:hdc1r2m35u) - jardiance is indicated: - to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. - to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. - as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. limitations of use jardiance is not recommended in patients with type 1 diabetes mellitus. it may increase the risk of diabetic ketoacidosis in these patients [see warnings and precautions (5.1)] . jardiance is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m2 . jardiance is likely to be ineffective in this setting based upon its mechanism of action. jardiance is contraindicated in patients: - with a hypersensitivity to empagliflozin or any of the excipients in jardiance, reactions such as angioedema have occurred [se

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - linagliptin (unii: 3x29zej4r2) (linagliptin - unii:3x29zej4r2) - tradjenta is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. limitations of use tradjenta is not recommended in patients with type 1 diabetes mellitus as it would not be effective. tradjenta has not been studied in patients with a history of pancreatitis. it is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using tradjenta [see warnings and precautions (5.1)]. tradjenta is contraindicated in patients with hypersensitivity to linagliptin or any of the excipients in tradjenta, reactions such as anaphylaxis, angioedema, exfoliative skin conditions, urticaria, or bronchial hyperreactivity have occurred [see warnings and precautions (5.3) and adverse reactions (6)]. risk summary the limited data with tradjenta use in pregnant women are not sufficient to inform of drug-associated risk for major birth defects and miscarriage. there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy [see clinical considerations]. in animal reproduction studies, no adverse developmental effects were observed when linagliptin was administered to pregnant rats during the period of organogenesis at doses similar to the maximum recommended clinical dose, based on exposure [see data] . the estimated background risk of major birth defects is 6% to 10% in women with pre-gestational diabetes with a hba1c >7 and has been reported to be as high as 20% to 25% in women with hba1c >10. the estimated background risk of 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. clinical considerations disease-associated maternal and/or embryo/fetal risk poorly controlled diabetes in pregnancy increases the maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, and delivery complications. poorly controlled diabetes increases the fetal risk for major birth defects, stillbirth, and macrosomia related morbidity. data animal data no adverse developmental outcome was observed when linagliptin was administered to pregnant wistar han rats and himalayan rabbits during the period of organogenesis at doses up to 240 mg/kg/day and 150 mg/kg/day, respectively. these doses represent approximately 943-times (rats) and 1,943-times (rabbits) the 5 mg maximum clinical dose, based on exposure. no adverse functional, behavioral, or reproductive outcome was observed in offspring following administration of linagliptin to wistar han rats from gestation day 6 to lactation day 21 at a dose 49-times the maximum recommended human dose, based on exposure. linagliptin crosses the placenta into the fetus following oral dosing in pregnant rats and rabbits. risk summary there is no information regarding the presence of linagliptin in human milk, the effects on the breastfed infant, or the effects on milk production. however, linagliptin is present in rat milk. therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for tradjenta and any potential adverse effects on the breastfed child from tradjenta or from the underlying maternal condition. the safety and effectiveness of tradjenta have not been established in pediatric patients. effectiveness of tradjenta was not demonstrated in a 26-week randomized, double-blind, placebo-controlled trial (nct03429543) in 157 pediatric patients aged 10 to 17 years with inadequately controlled type 2 diabetes mellitus. in linagliptin studies, 1,085 linagliptin-treated patients were 65 years of age and older and 131 patients were 75 years of age and older. in these linagliptin studies, no overall differences in safety or effectiveness of linagliptin were observed between geriatric patients and younger adult patients. no dosage adjustment is recommended for patients with renal impairment [see clinical pharmacology (12.3)]. in the tradjenta treatment arm of the carmelina trial [see clinical studies (14)] , 2,200 (63%) patients had renal impairment (egfr <60 ml/min/1.73 m2 ). approximately 20% of the population had egfr ≥45 to <60 ml/min/1.73 m2 , 28% of the population had egfr ≥30 to <45 ml/min/1.73 m2 and 15% had egfr <30 ml/min/1.73 m2 . the overall incidence of adverse reactions were generally similar between the tradjenta and placebo treatment arms. no dose adjustment is recommended for patients with hepatic impairment [see clinical pharmacology (12.3)] .

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - rivaroxaban (unii: 9ndf7jz4m3) (rivaroxaban - unii:9ndf7jz4m3) - xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. there are limited data on the relative effectiveness of xarelto and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled [see clinical studies (14.1)]. xarelto is indicated for the treatment of deep vein thrombosis (dvt). xarelto is indicated for the treatment of pulmonary embolism (pe). xarelto is indicated for the reduction in the risk of recurrence of dvt and/or pe in patients at continued risk for recurrent dvt and/or pe after completion of initial treatment lasting at least 6 months. xarelto is indicated for the prophylaxis of dvt, which may lead to pe in patients undergoing knee or hip replacement surgery. xarelto is indicated for the prophylaxis of venous thromboembolism (vte) and vte related death during hospitalization and post hospital discharge in adult patients admitted for an acute medical illness who are at risk for thromboemb

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - rivaroxaban (unii: 9ndf7jz4m3) (rivaroxaban - unii:9ndf7jz4m3) - xarelto is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. there are limited data on the relative effectiveness of xarelto and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled [see clinical studies (14.1)]. xarelto is indicated for the treatment of deep vein thrombosis (dvt). xarelto is indicated for the treatment of pulmonary embolism (pe). xarelto is indicated for the reduction in the risk of recurrence of dvt and/or pe in patients at continued risk for recurrent dvt and/or pe after completion of initial treatment lasting at least 6 months. xarelto is indicated for the prophylaxis of dvt, which may lead to pe in patients undergoing knee or hip replacement surgery. xarelto is indicated for the prophylaxis of venous thromboembolism (vte) and vte related death during hospitalization and post hospital discharge in adult patients admitted for an acute medical illness who are at risk for thromboemb

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - empagliflozin (unii: hdc1r2m35u) (empagliflozin - unii:hdc1r2m35u) - jardiance is indicated: - to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure. - to reduce the risk of cardiovascular death in adults with type 2 diabetes mellitus and established cardiovascular disease. - as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus. limitations of use jardiance is not recommended in patients with type 1 diabetes mellitus. it may increase the risk of diabetic ketoacidosis in these patients [see warnings and precautions (5.1)] . jardiance is not recommended for use to improve glycemic control in patients with type 2 diabetes mellitus with an egfr less than 30 ml/min/1.73 m2 . jardiance is likely to be ineffective in this setting based upon its mechanism of action. jardiance is contraindicated in patients: - with a hypersensitivity to empagliflozin or any of the excipients in jardiance, reactions such as angioedema have occurred [se

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - varenicline tartrate (unii: 82269asb48) (varenicline - unii:w6hs99o8zo) - chantix is indicated for use as an aid to smoking cessation treatment. chantix is contraindicated in patients with a known history of serious hypersensitivity reactions or skin reactions to chantix. risk summary available data have not suggested an increased risk for major birth defects following exposure to varenicline in pregnancy, compared with women who smoke [see data]. smoking during pregnancy is associated with maternal, fetal, and neonatal risks (see clinical considerations) . in animal studies, varenicline did not result in major malformations but caused decreased fetal weights in rabbits when dosed during organogenesis at exposures equivalent to 50 times the exposure at the maximum recommended human dose (mrhd). additionally, administration of varenicline to pregnant rats during organogenesis through lactation produced developmental toxicity in offspring at maternal exposures equivalent to 36 times human exposure at the mrhd [see data] . the estimated background risk of oral clefts is increased by

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - dabigatran etexilate mesylate (unii: sc7nuw5iit) (dabigatran - unii:i0vm4m70gc) - pradaxa capsules is indicated to reduce the risk of stroke and systemic embolism in adult patients with non-valvular atrial fibrillation. pradaxa capsules is indicated for the treatment of deep venous thrombosis and pulmonary embolism in adult patients who have been treated with a parenteral anticoagulant for 5-10 days. pradaxa capsules is indicated to reduce the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients who have been previously treated. pradaxa capsules is indicated for the prophylaxis of deep vein thrombosis and pulmonary embolism in adult patients who have undergone hip replacement surgery. pradaxa capsules is indicated for the treatment of venous thromboembolic events (vte) in pediatric patients 8 to less than 18 years of age who have been treated with a parenteral anticoagulant for at least 5 days [see dosage and administration (2.3)] . pradaxa capsules is indicated to reduce the risk of recurrence of vte in pediatric patients 8 to less than 18 years of age who have been previously treated [see dosage and administration (2.3)] . pradaxa is contraindicated in patients with: - active pathological bleeding [see warnings and precautions (5.2) and adverse reactions (6.1)] - history of a serious hypersensitivity reaction to dabigatran, dabigatran etexilate, or to one of the excipients of the product (e.g., anaphylactic reaction or anaphylactic shock) [see adverse reactions (6.1)] - mechanical prosthetic heart valve [see warnings and precautions (5.4)] risk summary the limited available data on pradaxa use in pregnant women are insufficient to determine drug-associated risks for adverse developmental outcomes. there are risks to the mother associated with untreated venous thromboembolism in pregnancy and a risk of hemorrhage in the mother and fetus associated with the use of anticoagulants (see clinical considerations) . in pregnant rats treated from implantation until weaning, dabigatran increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition at an exposure 2.6 times the human exposure. at a similar exposure, dabigatran decreased the number of implantations when rats were treated prior to mating and up to implantation (gestation day 6). dabigatran administered to pregnant rats and rabbits during organogenesis up to exposures 8 and 13 times the human exposure, respectively, did not induce major malformations. however, the incidence of delayed or irregular ossification of fetal skull bones and vertebrae was increased in the rat (see data) . the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%-4% and 15%-20%, respectively. clinical considerations disease-associated maternal and/or embryo/fetal risk pregnancy confers an increased risk for thromboembolism that is higher for women with underlying thromboembolic disease and certain high-risk pregnancy conditions. published data describe that women with a previous history of venous thrombosis are at high risk for recurrence during pregnancy. fetal/neonatal adverse reaction use of anticoagulants, including pradaxa, may increase the risk of bleeding in the fetus and neonate. monitor neonates for bleeding [see warnings and precautions (5.2)]. labor or delivery all patients receiving anticoagulants, including pregnant women, are at risk for bleeding. pradaxa use during labor or delivery in women who are receiving neuraxial anesthesia may result in epidural or spinal hematomas. consider discontinuation or use of shorter acting anticoagulant as delivery approaches [see warnings and precautions (5.2, 5.3)] . data animal data dabigatran has been shown to decrease the number of implantations when male and female rats were treated at a dosage of 70 mg/kg (about 2.6 to 3.0 times the human exposure at mrhd of 300 mg/day based on area under the curve [auc] comparisons) prior to mating and up to implantation (gestation day 6). treatment of pregnant rats after implantation with dabigatran at the same dose increased the number of dead offspring and caused excess vaginal/uterine bleeding close to parturition. dabigatran administered to pregnant rats and rabbits during organogenesis up to maternally toxic doses of 200 mg/kg (8 and 13 times the human exposure, respectively, at a mrhd of 300 mg/day based on auc comparisons) did not induce major malformations, but increased the incidence of delayed or irregular ossification of fetal skull bones and vertebrae in the rat. death of offspring and mother rats during labor in association with uterine bleeding occurred during treatment of pregnant rats from implantation (gestation day 7) to weaning (lactation day 21) with dabigatran at a dose of 70 mg/kg (about 2.6 times the human exposure at mrhd of 300 mg/day based on auc comparisons). risk summary there are no data on the presence of dabigatran in human milk, the effects on the breastfed child, or on milk production. dabigatran and/or its metabolites were present in rat milk. breastfeeding is not recommended during treatment with pradaxa. females of reproductive potential requiring anticoagulation should discuss pregnancy planning with their physician. the risk of clinically significant uterine bleeding, potentially requiring gynecological surgical interventions, identified with oral anticoagulants including pradaxa should be assessed in females of reproductive potential and those with abnormal uterine bleeding. the safety and effectiveness of pradaxa capsules for the treatment and the reduction in risk of recurrence of venous thromboembolism have been established in pediatric patients 8 to less than 18 years of age. use of pradaxa for this indication is supported by evidence from adequate and well-controlled studies in pediatric patients. these studies included an open-label, randomized, parallel-group study and an open-label, single-arm safety study [see adverse reactions (6.1) and clinical studies (14.4, 14.5)] . other age-appropriate pediatric dosage forms of dabigatran etexilate are available for pediatric patients less than 8 years of age for these indications. safety and effectiveness of pradaxa capsules have not been established in pediatric patients with non-valvular atrial fibrillation or those who have undergone hip replacement surgery. of the total number of patients in the re-ly study, 82% were 65 and over, while 40% were 75 and over. the risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups [see warnings and precautions (5), adverse reactions (6.1), and clinical studies (14.1)] . reduction of risk of stroke and systemic embolism in non-valvular atrial fibrillation in adult patients no dose adjustment of pradaxa is recommended in patients with mild or moderate renal impairment [see clinical pharmacology (12.3)] . reduce the dose of pradaxa in patients with severe renal impairment (crcl 15-30 ml/min) [see dosage and administration (2.2, 2.4) and clinical pharmacology (12.3)] . dosing recommendations for patients with crcl < 15 ml/min or on dialysis cannot be provided. adjust dose appropriately in patients with renal impairment receiving concomitant p-gp inhibitors [see warnings and precautions (5.5), drug interactions (7.1), and clinical pharmacology (12.3)]. treatment and reduction in the risk of recurrence of deep venous thrombosis and pulmonary embolism in adult patients patients with severe renal impairment (crcl ≤ 30 ml/min) were excluded from re-cover. dosing recommendations for patients with crcl ≤ 30 ml/min or on dialysis cannot be provided. avoid use of pradaxa with concomitant p-gp inhibitors in patients with crcl < 50 ml/min [see warnings and precautions (5.5), drug interactions (7.2), and clinical pharmacology (12.3)]. prophylaxis of deep vein thrombosis and pulmonary embolism in adult patients following hip replacement surgery patients with severe renal impairment (crcl < 30 ml/min) were excluded from re-novate and re-novate ii. dosing recommendations for patients with crcl < 30 ml/min or on dialysis cannot be provided. avoid use of pradaxa with concomitant p-gp inhibitors in patients with crcl < 50 ml/min [see warnings and precautions (5.5), drug interactions (7.3), and clinical pharmacology (12.2, 12.3)]. treatment and reduction in the risk of recurrence of vte in pediatric patients pradaxa has not been studied in pediatric patients with egfr < 50 ml/min/1.73 m2 . reduced renal function could increase exposure. dosing recommendations cannot be provided for treatment of these patients. avoid use of pradaxa capsules in these patients [see dosage and administration (2.4)].

미국 - 영어 - NLM (National Library of Medicine)

a-s medication solutions - ketorolac tromethamine (unii: 4eve5946bq) (ketorolac - unii:yzi5105v0l) - carefully consider the potential benefits and risks of ketorolac tromethamine and other treatment options before deciding to use ketorolac. use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see warnings ). ketorolac tromethamine is indicated for the short-term (≤5 days) management of moderately severe acute pain that requires analgesia at the opioid level, usually in a postoperative setting. therapy should always be initiated with intravenous or intramuscular dosing of ketorolac tromethamine, and oral ketorolac tromethamine is to be used only as continuation treatment, if necessary. the total combined duration of use of ketorolac tromethamine injection, and oral ketorolac tromethamine is not to exceed 5 days of use because of the potential of increasing the frequency and severity of adverse reactions associated with the recommended doses (see warnings, precautions, dosage and administration , and adverse reactions ). patients should be switched to alternative analgesics as soon as possible, but ketorolac tromethamine therapy is not to exceed 5 days. (see also boxed warning ) ketorolac tromethamine is contraindicated in patients with previously demonstrated hypersensitivity to ketorolac tromethamine. ketorolac tromethamine is contraindicated in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. ketorolac tromethamine should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other nsaids. severe, rarely fatal, anaphylactic-like reactions to nsaids have been reported in such patients (see warnings, anaphylactoid reactions , and precautions, pre-existing asthma ). ketorolac tromethamine is contraindicated as prophylactic analgesic before any major surgery. ketorolac tromethamine is contraindicated in the setting of coronary artery bypass graft (cabg) surgery (see warnings ). ketorolac tromethamine is contraindicated in patients with advanced renal impairment or in patients at risk for renal failure due to volume depletion (see warnings for correction of volume depletion). ketorolac tromethamine is contraindicated in labor and delivery because, through its prostaglandin synthesis inhibitory effect, it may adversely affect fetal circulation and inhibit uterine musculature, thus increasing the risk of uterine hemorrhage. ketorolac tromethamine inhibits platelet function and is, therefore, contraindicated in patients with suspected or confirmed cerebrovascular bleeding, hemorrhagic diathesis, incomplete hemostasis and those at high risk of bleeding (see warnings and precautions ). ketorolac tromethamine is contraindicated in patients currently receiving aspirin or nsaids because of the cumulative risks of inducing serious nsaid-related adverse events. the concomitant use of ketorolac tromethamine and probenecid is contraindicated. the concomitant use of ketorolac tromethamine and pentoxifylline is contraindicated. ketorolac tromethamine injection is contraindicated for neuraxial (epidural or intrathecal) administration due to its alcohol content.