USA - engelsk - NLM (National Library of Medicine)

bayer healthcare pharmaceuticals inc. - gadobutrol (unii: 1bj477io2l) (gadolinium cation (3+) - unii:azv954tz9n) - gadobutrol 604.72 mg in 1 ml - gadavist is indicated for use with magnetic resonance imaging (mri) in adult and pediatric patients, including term neonates to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. gadavist is indicated for use with mri in adult patients to assess the presence and extent of malignant breast disease. gadavist is indicated for use in magnetic resonance angiography (mra) in adult and pediatric patients, including term neonates, to evaluate known or suspected supra-aortic or renal artery disease . gadavist is indicated for use in cardiac mri (cmri) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (cad). gadavist is contraindicated in patients with history of severe hypersensitivity reactions to gadavist. gbcas cross the placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see data). because of the potential risks of gadolinium to the fetus, use gadavist only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and is 15 to 20%, respectively. contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the maternal indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). in rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses). because pregnant animals received repeated daily doses of gadavist, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans there are no data on the presence of gadobutrol in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited gbca gastrointestinal absorption in the breast-fed infant. gadobutrol is present in rat milk (see data). the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for gadavist and any potential adverse effects on the breastfed infant from gadavist or from the underlying maternal condition. in lactating rats receiving 0.5 mmol/kg of intravenous [153 gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk within 3 hours after administration, and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). the safety and effectiveness of gadavist have been established in pediatric patients, including term neonates, for use with mri to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system and for use in mra to evaluate known or suspected supra-aortic or renal artery disease. use of gadavist in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with cns and non-cns lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see clinical pharmacology (12.3) and clinical studies (14.1) ]. the frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [see adverse reactions (6.1)] . no dose adjustment according to age is necessary in pediatric patients [see dosage and administration (2.1), clinical pharmacology (12.3), and clinical studies (14.1)] . the safety and effectiveness of gadavist have not been established in preterm neonates for any indication or in pediatric patients of any age for use with mri to assess the presence and extent of malignant breast disease, or for use in cmri to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (cad). no case of nsf associated with gadavist or any other gbca has been identified in pediatric patients ages 6 years and younger. pharmacokinetic studies suggest that clearance of gadavist is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. no increased risk factor for nsf has been identified in juvenile animal studies of gadobutrol. normal estimated gfr (egfr) is around 30 ml/min/1.73m2 at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum egfr: 31 ml/min/1.73m2 (age 2 to 7 days), 38 ml/min/1.73m2 (age 8 to 28 days), 62 ml/min/1.73m2 (age 1 to 6 months), and 83 ml/min/1.73m2 (age 6 to 12 months). single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of gadavist, 1,377 patients were 65 years of age and over, while 104 patients  were 80 years of age and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use of gadavist in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. no dose adjustment according to age is necessary in this population. prior to administration of gadavist, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests [see warnings and precautions (5.2)] . no dosage adjustment is recommended for patients with renal impairment. gadavist can be removed from the body by hemodialysis [see warnings and precautions (5.2) and clinical pharmacology (12.3)] .

USA - engelsk - NLM (National Library of Medicine)

bayer healthcare pharmaceuticals inc. - gadopentetate dimeglumine (unii: rh248g8v27) (gadopentetate - unii:v7ok6j19hq) - magnevist injection is indicated for use with magnetic resonance imaging (mri) in adults, and pediatric patients (2 years of age and older) to visualize lesions with abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. magnevist injection has been shown to facilitate visualization of intracranial lesions including but not limited to tumors. magnevist injection is indicated for use with mri in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the head and neck. magnevist injection is indicated for use in mri in adults and pediatric patients (2 years of age and older) to facilitate the visualization of lesions with abnormal vascularity in the body. magnevist is contraindicated in patients with: gbcas cross the placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data). in animal

USA - engelsk - NLM (National Library of Medicine)

bayer healthcare pharmaceuticals inc. - gadobutrol (unii: 1bj477io2l) (gadolinium cation (3+) - unii:azv954tz9n) - gadavist is indicated for use with magnetic resonance imaging (mri) in adult and pediatric patients, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. gadavist is indicated for use with mri in adult patients to assess the presence and extent of malignant breast disease. gadavist is indicated for use in magnetic resonance angiography (mra) in adult and pediatric patients (including term neonates) to evaluate known or suspected supra-aortic or renal artery disease. gadavist is indicated for use in cardiac mri (cmri) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (cad). gadavist is contraindicated in patients with history of severe hypersensitivity reactions to gadavist. gbcas cross the placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see data). because of the potential risks of gadolinium to the fetus, use gadavist only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and is 15 to 20%, respectively. contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the maternal indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). in rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses). because pregnant animals received repeated daily doses of gadavist, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. there are no data on the presence of gadobutrol in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited gbca gastrointestinal absorption in the breast-fed infant. gadobutrol is present in rat milk (see data). the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for gadavist and any potential adverse effects on the breastfed infant from gadavist or from the underlying maternal condition. in lactating rats receiving 0.5 mmol/kg of intravenous [153 gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk within 3 hours after administration, and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). the safety and effectiveness of gadavist have been established in pediatric patients, including term neonates, for use with mri to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system and for use in mra to evaluate known or suspected supra-aortic or renal artery disease. use of gadavist in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with cns and non-cns lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see clinical pharmacology (12.3) and clinical studies (14.1)] . the frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [ see adverse reactions (6.1)] . no dose adjustment according to age is necessary in pediatric patients [see dosage and administration (2.1), clinical pharmacology (12.3), and clinical studies (14.1)] . the safety and effectiveness of gadavist have not been established in preterm neonates for any indication or in pediatric patients of any age for use with mri to assess the presence and extent of malignant breast disease, or for use in cmri to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (cad). no case of nsf associated with gadavist or any other gbca has been identified in pediatric patients ages 6 years and younger. pharmacokinetic studies suggest that clearance of gadavist is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. no increased risk factor for nsf has been identified in juvenile animal studies of gadobutrol. normal estimated gfr (egfr) is around 30 ml/min/1.73m2 at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum egfr: 31 ml/min/1.73m2 (age 2 to 7 days), 38 ml/min/1.73m2 (age 8 to 28 days), 62 ml/min/1.73m2 (age 1 to 6 months), and 83 ml/min/1.73m2 (age 6 to 12 months). single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of gadavist, 1,377 patients were 65 years of age and over, while 104 patients were 80 years of age and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use of gadavist in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. no dose adjustment according to age is necessary in this population. prior to administration of gadavist, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests [see warnings and precautions (5.2)] . no dosage adjustment is recommended for patients with renal impairment. gadavist can be removed from the body by hemodialysis [see warnings and precautions (5.2) and clinical pharmacology (12.3)].

USA - engelsk - NLM (National Library of Medicine)

ge healthcare inc. - gadodiamide (unii: 84f6u3j2r6) (gadodiamide - unii:84f6u3j2r6) - omniscan is a gadolinium-based contrast agent indicated for intravenous use in mri to visualize lesions with abnormal vascularity (or those thought to cause abnormalities in the blood-brain barrier) in the brain (intracranial lesions), spine, and associated tissues [see clinical studies (14.1)]. omniscan is a gadolinium-based contrast agent indicated for intravenous use in mri to facilitate the visualization of lesions with abnormal vascularity within the thoracic (noncardiac), abdominal, pelvic cavities, and the retroperitoneal space [see clinical studies (14.2)]. omniscan is contraindicated in patients with: - chronic, severe kidney disease (glomerular filtration rate, gfr < 30 ml/min/1.73m2 ) or acute kidney injury - prior hypersensitivity to omniscan risk summary gbcas cross the human placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, no adverse fetal effects were observed with administration of gadodiamide to pregnant rats during organogenesis at doses 1.3 times the maximum human dose based on body surface area (see data) . because of the potential risks of gadolinium to the fetus, use omniscan only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. all pregnancies have a background risk of birth defect, loss, or other adverse outcomes. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. data human data contrast enhancement is visualized in the human placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the maternal indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. animal data gadolinium retention gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one-month postnatal age. reproductive toxicology gadodiamide has been shown to have an adverse effect on embryo-fetal development in rabbits at dosages as low as 0.5 mmol/kg/day for 13 days during gestation (approximately 0.6 times the human dose based on a body surface area comparison). these adverse effects are observed as an increased incidence of flexed appendages and skeletal malformations which may be due to maternal toxicity since the body weight of the dams was reduced in response to gadodiamide administration during pregnancy. in rat studies, fetal abnormalities were not observed at doses up to 2.5 mmol/kg/day for 10 days during gestation (1.3 times the maximum human dose based on a body surface area comparison); however, maternal toxicity was not achieved in these studies and a definitive conclusion about teratogenicity in rats at doses above 2.5 mmol/kg/day cannot be made. risk summary there are no data on the presence of gadodiamide in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is excreted in breast milk. additionally, there is limited gbca gastrointestinal absorption in the breast-fed infant. animal data show transfer of gadodiamide into rat milk (see data). the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for omniscan and any potential adverse effects on the breastfed infant from omniscan or from the underlying maternal condition. data gadodiamide is detected in the breast milk of rats injected intravenously with 0.3 mmol/kg up to 4 hours post dosing and is below the level of quantification after 8 hours. the safety and efficacy of omniscan at a single dose of 0.05 to 0.1 mmol/kg have been established in pediatric patients over 2 years of age based on adequate and well controlled studies of omniscan in adults, a pediatric cns imaging study, and safety data in the scientific literature. however, the safety and efficacy of doses greater than 0.1 mmol/kg and of repeated doses have not been studied in pediatric patients. pharmacokinetics of omniscan have not been studied in pediatrics. the glomerular filtration rate of neonates and infants is much lower than that of adults. the pharmacokinetics volume of distribution is also different. therefore, the optimal dosing regimen and imaging times in patients under 2 years of age have not been established. in clinical studies of omniscan, 243 patients were between 65 and 80 years of age while 15 were over 80 years of age. no overall differences in safety or effectiveness were observed between these patients and younger patients. other reported clinical experience has not identified differences in response between the elderly and younger patients, but greater sensitivity in the elderly cannot be ruled out. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant disease or other drug therapy. omniscan is excreted by the kidney, and the risk of toxic reactions to omniscan may be greater in patients with impaired renal function [see warnings and precautions (5.4)]. because elderly patients are more likely to have decreased renal function, select dose carefully and consider assessment of renal function before omniscan use. dose adjustments in renal or hepatic impairment have not been studied. caution should be exercised in patients with impaired renal insufficiency [see warnings and precautions (5.2, 5.5)].

USA - engelsk - NLM (National Library of Medicine)

ge healthcare - gadoterate meglumine (unii: l0nd3981ag) (gadolinium cation (3+) - unii:azv954tz9n) - clariscan is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (mri) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (bbb) and/or abnormal vascularity. history of clinically important hypersensitivity reactions to clariscan [see warnings and precautions (5.2)]. risk summary gbcas cross the human placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadoterate meglumine during organogenesis at doses up to 16 and 10 times, respectively, the recommended human dose (see data) . because of the potential risks of gadolinium to the fetus, use clariscan only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population(s) are 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. data human data contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the material indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. animal data gadolinium retention gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one-month postnatal age. reproductive toxicology gadoterate meglumine was administered in intravenous doses of 0, 2, 4 and 10 mmol/kg/day [3, 7 and 16 times the recommended human dose (rhd) based on body surface area (bsa)] to female rats for 14 days before mating, throughout the mating period and until gestation day (gd) 17. pregnant rabbits were administered gadoterate meglumine in intravenous doses of 0, 1, 3 and 7 mmol/kg/day (3, 10 and 23 times the rhd based on bsa) from gd6 to gd19. no effects on embryo-fetal development were observed at doses up to 10 mmol/kg/day in rats and 3 mmol/kg/day in rabbits. maternal toxicity was observed in rats at 10 mmol/kg/day and in rabbits at 7 mmol/kg/day. this maternal toxicity was characterized in rats by a slightly lower litter size and gravid uterus weight compared to the control group, and in rabbits by a reduction in body weight and food consumption. risk summary there are no data on the presence of gadoterate in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is excreted in breast milk. additionally, there is limited gbca gastrointestinal absorption in the breastfed infant. gadoterate is present in goat milk (see data ). the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clariscan and any potential adverse effects on the breastfed infant from clariscan or from the underlying maternal condition. data nonclinical data demonstrate that gadoterate is detected in goat milk in amounts < 0.1% of the dose intravenously administered. furthermore, in rats, absorption of gadoterate via the gastrointestinal tract is poor (1.2% of the administered dose was absorbed and eliminated in urine). the safety and efficacy of gadoterate meglumine at a single dose of 0.1 mmol/kg have been established in pediatric patients from birth (term neonates ≥ 37 weeks gestational age) to 17 years of age based on clinical data in 133 pediatric patients 2 years of age and older, and clinical data in 52 pediatric patients birth to less than 2 years of age that supported extrapolation from adult data [see clinical studies (14)] . adverse reactions in pediatric patients were similar to those reported in adults [see adverse reactions (6.1)] . no dosage adjustment according to age is necessary in pediatric patients [see dosage and administration (2.1), pharmacokinetics (12.3)] . the safety of gadoterate meglumine has not been established in preterm neonates. no cases of nsf associated with gadoterate meglumine or any other gbca have been identified in pediatric patients age 6 years and younger [see warnings and precautions (5.1)] . normal estimated gfr (egfr) is approximately 30 ml/minute/1.73 m2 at birth and increases to adult values by 2 years of age. juvenile animal data single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of gadoterate meglumine, 900 patients were 65 years of age and over, and 304 patients were 75 years of age and over. no overall differences in safety or efficacy were observed between these subjects and younger subjects. in general, use of clariscan in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. no age-related dosage adjustment is necessary. no clariscan dosage adjustment is recommended for patients with renal impairment. gadoterate meglumine can be removed from the body by hemodialysis [see warnings and precautions (5.1) and clinical pharmacology (12.3)].

USA - engelsk - NLM (National Library of Medicine)

bayer healthcare pharmaceuticals inc. - gadobutrol (unii: 1bj477io2l) (gadolinium cation (3+) - unii:azv954tz9n) - gadavist is indicated for use with magnetic resonance imaging (mri) in adult and pediatric patients, including term neonates, to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system. gadavist is indicated for use with mri in adult patients to assess the presence and extent of malignant breast disease. gadavist is indicated for use in magnetic resonance angiography (mra) in adult and pediatric patients (including term neonates) to evaluate known or suspected supra-aortic or renal artery disease. gadavist is indicated for use in cardiac mri (cmri) to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in adult patients with known or suspected coronary artery disease (cad). gadavist is contraindicated in patients with history of severe hypersensitivity reactions to gadavist. gbcas cross the placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, although teratogenicity was not observed, embryolethality was observed in monkeys, rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 times and above the recommended human dose. retardation of embryonal development was observed in rabbits and rats receiving intravenous gadobutrol during organogenesis at doses 8 and 12 times, respectively, the recommended human dose (see data). because of the potential risks of gadolinium to the fetus, use gadavist only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population is unknown. in the u.s. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and is 15 to 20%, respectively. contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the maternal indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one month postnatal age. embryolethality was observed when gadobutrol was administered intravenously to monkeys during organogenesis at doses 8 times the recommended single human dose (based on body surface area); gadobutrol was not maternally toxic or teratogenic at this dose. embryolethality and retardation of embryonal development also occurred in pregnant rats receiving maternally toxic doses of gadobutrol (≥ 7.5 mmol/kg body weight; equivalent to 12 times the human dose based on body surface area) and in pregnant rabbits (≥ 2.5 mmol/kg body weight; equivalent to 8 times the recommended human dose based on body surface area). in rabbits, this finding occurred without evidence of pronounced maternal toxicity and with minimal placental transfer (0.01% of the administered dose detected in the fetuses). because pregnant animals received repeated daily doses of gadavist, their overall exposure was significantly higher than that achieved with the standard single dose administered to humans. there are no data on the presence of gadobutrol in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk and there is limited gbca gastrointestinal absorption in the breast-fed infant. gadobutrol is present in rat milk (see data). the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for gadavist and any potential adverse effects on the breastfed infant from gadavist or from the underlying maternal condition. in lactating rats receiving 0.5 mmol/kg of intravenous [153 gd]-gadobutrol, 0.01% of the total administered radioactivity was transferred to the pup via maternal milk within 3 hours after administration, and the gastrointestinal absorption is poor (approximately 5% of the dose orally administered was excreted in the urine). the safety and effectiveness of gadavist have been established in pediatric patients, including term neonates, for use with mri to detect and visualize areas with disrupted blood brain barrier and/or abnormal vascularity of the central nervous system and for use in mra to evaluate known or suspected supra-aortic or renal artery disease. use of gadavist in these indications is supported by adequate and well-controlled studies in adults and supportive imaging data in two studies in 135 patients 2 to less than 18 years of age and 44 patients less than 2 years of age with cns and non-cns lesions, and pharmacokinetic data in 130 patients 2 to less than 18 years of age and 43 patients less than 2 years of age, including term neonates [see clinical pharmacology (12.3) and clinical studies (14.1)] . the frequency, type, and severity of adverse reactions in pediatric patients were similar to adverse reactions in adults [ see adverse reactions (6.1)] . no dose adjustment according to age is necessary in pediatric patients [see dosage and administration (2.1), clinical pharmacology (12.3), and clinical studies (14.1)] . the safety and effectiveness of gadavist have not been established in preterm neonates for any indication or in pediatric patients of any age for use with mri to assess the presence and extent of malignant breast disease, or for use in cmri to assess myocardial perfusion (stress, rest) and late gadolinium enhancement in patients with known or suspected coronary artery disease (cad). no case of nsf associated with gadavist or any other gbca has been identified in pediatric patients ages 6 years and younger. pharmacokinetic studies suggest that clearance of gadavist is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. no increased risk factor for nsf has been identified in juvenile animal studies of gadobutrol. normal estimated gfr (egfr) is around 30 ml/min/1.73m2 at birth and increases to mature levels around 1 year of age, reflecting growth in both glomerular function and relative body surface area. clinical studies in pediatric patients younger than 1 year of age have been conducted in patients with the following minimum egfr: 31 ml/min/1.73m2 (age 2 to 7 days), 38 ml/min/1.73m2 (age 8 to 28 days), 62 ml/min/1.73m2 (age 1 to 6 months), and 83 ml/min/1.73m2 (age 6 to 12 months). single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of gadavist, 1,377 patients were 65 years of age and over, while 104 patients were 80 years of age and over. no overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, use of gadavist in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. no dose adjustment according to age is necessary in this population. prior to administration of gadavist, screen all patients for renal dysfunction by obtaining a history and/or laboratory tests [see warnings and precautions (5.2)] . no dosage adjustment is recommended for patients with renal impairment. gadavist can be removed from the body by hemodialysis [see warnings and precautions (5.1) and clinical pharmacology (12.3)].

USA - engelsk - NLM (National Library of Medicine)

ge healthcare - gadoterate meglumine (unii: l0nd3981ag) (gadolinium cation (3+) - unii:azv954tz9n) - clariscan is a gadolinium-based contrast agent indicated for intravenous use with magnetic resonance imaging (mri) in brain (intracranial), spine and associated tissues in adult and pediatric patients (including term neonates) to detect and visualize areas with disruption of the blood brain barrier (bbb) and/or abnormal vascularity. history of clinically important hypersensitivity reactions to clariscan [see warnings and precautions (5.2)]. risk summary gbcas cross the human placenta and result in fetal exposure and gadolinium retention. the human data on the association between gbcas and adverse fetal outcomes are limited and inconclusive (see data) . in animal reproduction studies, there were no adverse developmental effects observed in rats or rabbits with intravenous administration of gadoterate meglumine during organogenesis at doses of 16 and 10 times, respectively, the recommended human dose (see data) . because of the potential risks of gadolinium to the fetus, use clariscan only if imaging is essential during pregnancy and cannot be delayed. the estimated background risk of major birth defects and miscarriage for the indicated population(s) are 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. data human data contrast enhancement is visualized in the placenta and fetal tissues after maternal gbca administration. cohort studies and case reports on exposure to gbcas during pregnancy have not reported a clear association between gbcas and adverse effects in the exposed neonates. however, a retrospective cohort study, comparing pregnant women who had a gbca mri to pregnant women who did not have an mri, reported a higher occurrence of stillbirths and neonatal deaths in the group receiving gbca mri. limitations of this study include a lack of comparison with non-contrast mri and lack of information about the material indication for mri. overall, these data preclude a reliable evaluation of the potential risk of adverse fetal outcomes with the use of gbcas in pregnancy. animal data gadolinium retention gbcas administered to pregnant non-human primates (0.1 mmol/kg on gestational days 85 and 135) result in measurable gadolinium concentration in the offspring in bone, brain, skin, liver, kidney, and spleen for at least 7 months. gbcas administered to pregnant mice (2 mmol/kg daily on gestational days 16 through 19) result in measurable gadolinium concentrations in the pups in bone, brain, kidney, liver, blood, muscle, and spleen at one-month postnatal age. reproductive toxicology gadoterate meglumine was administered in intravenous doses of 0, 2, 4 and 10 mmol/kg/day [3, 7 and 16 times the recommended human dose (rhd) based on body surface area (bsa)] to female rats for 14 days before mating, throughout the mating period and until gestation day (gd) 17. pregnant rabbits were administered gadoterate meglumine in intravenous doses of 0, 1, 3 and 7 mmol/kg/day (3, 10 and 23 times the rhd based on bsa) from gd6 to gd19. no effects on embryo-fetal development were observed at doses up to 10 mmol/kg/day in rats and 3 mmol/kg/day in rabbits. maternal toxicity was observed in rats at 10 mmol/kg/day and in rabbits at 7 mmol/kg/day. this maternal toxicity was characterized in rats by a slightly lower litter size and gravid uterus weight compared to the control group, and in rabbits by a reduction in body weight and food consumption. risk summary there are no data on the presence of gadoterate in human milk, the effects on the breastfed infant, or the effects on milk production. however, published lactation data on other gbcas indicate that 0.01 to 0.04% of the maternal gadolinium dose is present in breast milk. additionally, there is limited gbca gastrointestinal absorption in the breastfed infant. gadoterate is present in goat milk (see data ). the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for clariscan and any potential adverse effects on the breastfed infant from clariscan or from the underlying maternal condition. data nonclinical data demonstrate that gadoterate is detected in goat milk in amounts of < 0.1% of the dose intravenously administered. furthermore, in rats, absorption of gadoterate via the gastrointestinal tract is poor (1.2% of the administered dose was absorbed and eliminated in urine). the safety and efficacy of gadoterate meglumine at a single dose of 0.1 mmol/kg have been established in pediatric patients from birth (term neonates ≥ 37 weeks gestational age) to 17 years of age based on clinical data in 133 pediatric patients 2 years of age and older, and clinical data in 52 pediatric patients birth to less than 2 years of age that supported extrapolation from adult data [see clinical studies (14)] . adverse reactions in pediatric patients were similar to those reported in adults [see adverse reactions (6.1)] . no dose adjustment according to age is necessary in pediatric patients [see dosage and administration (2.1), pharmacokinetics (12.3)] . the safety of gadoterate meglumine has not been established in preterm neonates. no cases of nsf associated with gadoterate meglumine or any other gbca have been identified in pediatric patients age 6 years and younger [see warnings and precautions (5.1)] . normal estimated gfr (egfr) is approximately 30 ml/minute/1.73 m2 at birth and increases to adult values by 2 years of age. juvenile animal data single and repeat-dose toxicity studies in neonatal and juvenile rats did not reveal findings suggestive of a specific risk for use in pediatric patients including term neonates and infants. in clinical studies of gadoterate meglumine, 900 patients were 65 years of age and over, and 304 patients were 75 years of age and over. no overall differences in safety or efficacy were observed between these subjects and younger subjects. in general, use of clariscan in elderly patients should be cautious, reflecting the greater frequency of impaired renal function and concomitant disease or other drug therapy. no age-related dosage adjustment is necessary. no clariscan dosage adjustment is recommended for patients with renal impairment. gadoterate can be removed from the body by hemodialysis [see warnings and precautions (5.1) and clinical pharmacology (12.3)].

Singapore - engelsk - HSA (Health Sciences Authority)

canon medical systems asia pte., ltd. - radiology / imaging - this device is indicated to acquire and display cross sectional volumes of the whole body, to include the head, with the capability to image whole organs in a single rotation. whole organs include but are not limited to brain, heart, pancreas, etc. the aquilion one has the capability to provide volume sets of the entire organ. these volume sets can be used to perform specialized studies, using indicated software/hardware, of the whole organ by a trained and qualified physician.

Singapore - engelsk - HSA (Health Sciences Authority)

unison collaborative pte. ltd. - general hospital - the lymphscanner is a non-invasive hand-held device intended to measure localized percentage water content (pwc) in edematous conditions of human skin after surgery for breast cancer or gynecological cancers. applicability ranges from undetectable preclinical edema to advanced edema. the device integrating the main unit and the easily cleaned measurement probe can be used to aid in forming a clinical judgement of skin edema at any soft tissue site of the body by a health care professional. the measurement results are displayed in seconds after applying the measurement probe on the skin surface. there are no restrictions to the number of repeated measurements that can be performed for the same subject. the lymphscanner is intended to be operated by healthcare professionals in professional health care facilities.

Den europeiske union - engelsk - EMA (European Medicines Agency)

ge healthcare as - flutemetamol (18f) - radionuclide imaging; alzheimer disease - diagnostic radiopharmaceuticals - this medicinal product is for diagnostic use only.vizamyl is a radiopharmaceutical medicinal product indicated for positron emission tomography (pet) imaging of β amyloid neuritic plaque density in the brains of adult patients with cognitive impairment who are being evaluated for alzheimer’s disease (ad) and other causes of cognitive impairment. vizamyl should be used in conjunction with a clinical evaluation.a negative scan indicates sparse or no plaques, which is not consistent with a diagnosis of ad.