Ireland - English - HPRA (Health Products Regulatory Authority)

agfa healthcare imaging agents gmbh - gadopentetate dimeglumine - solution for injection - 0.5 mmol/ml

Ireland - English - HPRA (Health Products Regulatory Authority)

sanochemia pharmazeutika ag - gadopentetate dimeglumine - solution for injection - 500

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

bayer australia ltd - dimeglumine gadopentetate -

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

bracco diagnostics inc - gadoteridol (unii: 0199mv609f) (gadoteridol - unii:0199mv609f) - gadoteridol 279.3 mg in 1 ml - prohance is indicated for magnetic resonance imaging (mri) in adults and pediatric patients including term neonates to visualize lesions with disrupted blood brain barrier and/or abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. prohance is indicated for mri in adults to visualize lesions in the head and neck. prohance is contraindicated in patients with known allergic or hypersensitivity reactions to prohance [see warnings and precautions (5.3)]. risk summary 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) . because of the potential risks of gadolinium to the fetus, use prohance only if imaging is essential during pregnancy and cannot be delayed. in animal reproduction studies in rats, gadoteridol doubled the incidence of post-implantation loss at up to 16 times the recommended human dose (rhd). there were no adverse developmental effects observed in rabbits with intravenous administration of gadoteridol during organogenesis at doses up to 19 times the recommended human dose of 0.1 mmol/kg (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 to 4% and is 15 to 20%, respectively. data human data contrast agent 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. 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 gadoteridol was administered in intravenous doses of 0, 0.375, 1.5, 6.0, and 10 mmol/kg/day [0.6, 2.4, 9.7, and 16 times the recommended human dose (rhd) based on body surface area (bsa)] to female rats from gestational day (gd)6 until gd17. gadoteridol at 10 mmol/kg/day for 12 days during gestation doubled the incidence of post-implantation loss. when rats were administered 6.0 or 10.0 mmol/kg/day for 12 days, an increase in spontaneous locomotor activity was observed in the offspring. pregnant rabbits were administered gadoteridol in intravenous doses of 0, 0.4, 1.5, and 6 mmol/kg/day (1.3, 4.8, and 19.4 times the rhd based on bsa) from gd6 to gd18. gadoteridol increased the incidence of spontaneous abortion and early delivery in rabbits administered 6 mmol/kg/day for 13 days during gestation. risk summary there are no data on the presence of gadoteridol 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. gadoteridol 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 prohance and any potential adverse effects on the breastfed infant from prohance or from the underlying maternal condition. data prohance excretion in the milk of lactating rats was evaluated at 30 minutes, 6 and 24 hours after intravenous administration of 0.1 mmol/kg of 153 gd-gadoteridol to nursing mothers. small amounts of compound were found in milk immediately after injection (0.14% of the id), with the amount declining to a low level 24 hours after injection (<0.01% of the id). the safety and effectiveness of prohance have been established for use with mri to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to 17 years of age. pediatric use is based on evidence of effectiveness in adults and in 103 pediatric patients 2 years of age and older, in addition to experience in 125 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)] . the safety and efficacy of > 0.1 mmol/kg, and sequential and/or repeat procedures have not been studied in pediatric patients [see indications and usage (1) and dosage and administration (2)] . no case of nsf associated with prohance or any other gbca has been identified in pediatric patients ages 6 years and younger. pharmacokinetic studies suggest that weight normalized clearance of prohance is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. 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 egrf; 59.37 ml/min/1.73m2 (age just after birth to < 30 days), 118.84 ml/min/1.73m2 (age 30 days to < 6 months), 140.44 ml/min/1.73m2 (age 6 to 12 months). of the total number of 2673 adult subjects in clinical studies of prohance, 22% were 65 and over. no overall differences in safety were observed between these elderly subjects and the younger subjects. prohance is known to be substantially excreted by the kidneys, and the risk of toxic reactions from prohance may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function. no prohance dosage adjustment is recommended for patients with renal impairment. gadoteridol can be removed from the body by hemodialysis [see warning and precautions (5.2) and clinical pharmacology (12.3)] .

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

ge healthcare inc. - gadodiamide (unii: 84f6u3j2r6) (gadodiamide - unii:84f6u3j2r6) - gadodiamide 287 mg in 1 ml - 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

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

bayer healthcare, inc. - gadofosveset trisodium (unii: xm33q67uvh) (gadofosveset - unii:e65rw73phs) - injection - 244 mg in 1 ml - vasovist is indicated for use as a contrast agent in magnetic resonance angiography (mra) to evaluate aortoiliac occlusive disease (aiod) in adults with known or suspected peripheral vascular disease [see clinical studies (14) ]. history of a prior allergic reaction to a gadolinium-based contrast agent. pregnancy category c there are no adequate and well-controlled studies of vasovist in pregnant women. in animal studies, pregnant rabbits treated with gadofosveset trisodium at doses 3 times the human dose (based on body surface area) experienced higher rates of fetal loss and resorptions. because animal reproduction studies are not always predictive of human response, only use vasovist during pregnancy if the diagnostic benefit justifies the potential risks to the fetus. in reproductive studies, pregnant rats and rabbits received gadofosveset trisodium at various doses up to approximately 11 (rats) and 21.5 (rabbits) times the human dose (based on body surface area). the highest dose resulted in maternal t

United Kingdom - English - MHRA (Medicines & Healthcare Products Regulatory Agency)

bayer plc - meglumine gadopentetate - solution for injection - .002mmol/1ml

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

ge healthcare inc. - gadodiamide (unii: 84f6u3j2r6) (gadodiamide - unii:84f6u3j2r6) - gadodiamide 287 mg in 1 ml - 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 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. because of the potential risks of gadolinium to the fetus, use omniscan only if imaging is essential during pregnancy and cannot be delayed. 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. 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. omniscan 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 omniscan 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. it is not known whether this drug is excreted in human milk. because many drugs are excreted in human milk, exercise caution when administering omniscan to a nursing woman. 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. 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) ].

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

bracco diagnostics inc - gadoteridol (unii: 0199mv609f) (gadoteridol - unii:0199mv609f) - prohance is indicated for magnetic resonance imaging (mri) in adults and pediatric patients including term neonates to visualize lesions with disrupted blood brain barrier and/or abnormal vascularity in the brain (intracranial lesions), spine and associated tissues. prohance is indicated for mri in adults to visualize lesions in the head and neck. prohance is contraindicated in patients with known allergic or hypersensitivity reactions to prohance [see warnings and precautions (5.3)]. risk summary 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). because of the potential risks of gadolinium to the fetus, use prohance only if imaging is essential during pregnancy and cannot be delayed. in animal reproduction studies in rats, gadoteridol doubled the incidence of post-implantation loss at up to 16 times the recommended human dose (rhd). there were no adverse developmental effects observed in rabbits with intravenous administration of gadoteridol during organogenesis at doses up to 19 times the recommended human dose of 0.1 mmol/kg (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 to 4% and is 15 to 20%, respectively. data human data contrast agent 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. 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 gadoteridol was administered in intravenous doses of 0, 0.375, 1.5, 6.0, and 10 mmol/kg/day [0.6, 2.4, 9.7, and 16 times the recommended human dose (rhd) based on body surface area (bsa)] to female rats from gestational day (gd)6 until gd17. gadoteridol at 10 mmol/kg/day for 12 days during gestation doubled the incidence of post-implantation loss. when rats were administered 6.0 or 10.0 mmol/kg/day for 12 days, an increase in spontaneous locomotor activity was observed in the offspring. pregnant rabbits were administered gadoteridol in intravenous doses of 0, 0.4, 1.5, and 6 mmol/kg/day (1.3, 4.8, and 19.4 times the rhd based on bsa) from gd6 to gd18. gadoteridol increased the incidence of spontaneous abortion and early delivery in rabbits administered 6 mmol/kg/day for 13 days during gestation. risk summary there are no data on the presence of gadoteridol 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. gadoteridol 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 prohance and any potential adverse effects on the breastfed infant from prohance or from the underlying maternal condition. data prohance excretion in the milk of lactating rats was evaluated at 30 minutes, 6 and 24 hours after intravenous administration of 0.1 mmol/kg of 153 gd-gadoteridol to nursing mothers. small amounts of compound were found in milk immediately after injection (0.14% of the id), with the amount declining to a low level 24 hours after injection (<0.01% of the id). the safety and effectiveness of prohance have been established for use with mri to visualize lesions with abnormal blood brain barrier or abnormal vascularity of the brain, spine, and associated tissues in pediatric patients from birth, including term neonates, to 17 years of age. pediatric use is based on evidence of effectiveness in adults and in 103 pediatric patients 2 years of age and older, in addition to experience in 125 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)] . the safety and efficacy of > 0.1 mmol/kg, and sequential and/or repeat procedures have not been studied in pediatric patients [see indications and usage (1) and dosage and administration (2)] . no case of nsf associated with prohance or any other gbca has been identified in pediatric patients ages 6 years and younger. pharmacokinetic studies suggest that weight normalized clearance of prohance is similar in pediatric patients and adults, including pediatric patients age younger than 2 years. 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 egrf; 59.37 ml/min/1.73m2 (age just after birth to < 30 days), 118.84 ml/min/1.73m2 (age 30 days to < 6 months), 140.44 ml/min/1.73m2 (age 6 to 12 months). of the total number of 2673 adult subjects in clinical studies of prohance, 22% were 65 and over. no overall differences in safety were observed between these elderly subjects and the younger subjects. prohance is known to be substantially excreted by the kidneys, and the risk of toxic reactions from prohance may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, it may be useful to monitor renal function. no prohance dosage adjustment is recommended for patients with renal impairment. gadoteridol can be removed from the body by hemodialysis [see warning and precautions (5.2) and clinical pharmacology (12.3)] .

United States - English - 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)].