USA - engelsk - NLM (National Library of Medicine)

bracco diagnostics inc - gadobenate dimeglumine (unii: 3q6ppc19po) (gadolinium cation (3+) - unii:azv954tz9n) - gadobenate dimeglumine 529 mg in 1 ml - multihance is indicated for intravenous use in magnetic resonance imaging (mri) of the central nervous system (cns) in adults and pediatric patients (including term neonates), to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. multihance is indicated for use in magnetic resonance angiography (mra) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease. multihance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents [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) . in animal reproduction studies, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to 6 times the recommended human dose. there were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose (see data) . because of the potential risks of gadolinium to the fetus, use multihance only if imaging is essential and cannot be delayed. 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 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. 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 gadobenate dimeglumine has been shown to be teratogenic in rabbits when administered intravenously at 2 mmol/kg/day (6 times the recommended human dose based on body surface area) during organogenesis (day 6 to 18) inducing microphthalmia/small eye and/or focal retinal fold in 3 fetuses from 3 separate litters. in addition, multihance administered intravenously at 3 mmol/kg/day (10 times the recommended human dose based on body surface area) has been shown to increase intrauterine deaths in rabbits. there was no evidence that multihance induced teratogenic effects in rats at doses up to 2 mmol/kg/day (3 times the recommended human dose based on body surface area), however, rat dams exhibited no systemic toxicity at this dose. there were no adverse effects on the birth, survival, growth, development and fertility of the f1 generation at doses up to 2 mmol/kg in a rat peri- and post-natal (segment iii) study. risk summary limited literature reports that breastfeeding after gadobenate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. additionally, there is limited gbca gastrointestinal absorption. the developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for multihance and any potential adverse effects on the breastfed infant from multihance or from the underlying maternal condition. multihance is approved for intravenous use for mri of the cns 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 less than 17 years of age. pediatric use is based on evidence of effectiveness in adults and in 202 pediatric patients 2 years of age and older, in addition to experience in 105 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 two years of age and older. for pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 ml/kg [see dosage and administration (2.1), pharmacokinetics (12.3)] . the safety of multihance has not been established in preterm neonates. of the total number of 4967 adult subjects in clinical studies of multihance, 33% were 65 or older. no overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. the drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to multihance 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.

USA - engelsk - 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)] .

USA - engelsk - 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)] .

USA - engelsk - NLM (National Library of Medicine)

bracco diagnostics inc - gadobenate dimeglumine (unii: 3q6ppc19po) (gadolinium cation (3+) - unii:azv954tz9n) - multihance is indicated for intravenous use in magnetic resonance imaging (mri) of the central nervous system (cns) in adults and pediatric patients (including term neonates), to visualize lesions with abnormal blood-brain barrier or abnormal vascularity of the brain, spine, and associated tissues. multihance is indicated for use in magnetic resonance angiography (mra) to evaluate adults with known or suspected renal or aorto-ilio-femoral occlusive vascular disease. multihance is contraindicated in patients with known allergic or hypersensitivity reactions to gadolinium-based contrast agents [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 ). in animal reproduction studies, gadobenate dimeglumine has been shown to be teratogenic in rabbits following repeated intravenous administration during organogenesis at doses up to 6 times the recommended human dose. there were no adverse developmental effects observed in rats with intravenous administration of gadobenate dimeglumine during organogenesis at doses up to three times the recommended human dose (see data). because of the potential risks of gadolinium to the fetus, use multihance only if imaging is essential and cannot be delayed. 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 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. 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 gadobenate dimeglumine has been shown to be teratogenic in rabbits when administered intravenously at 2 mmol/kg/day (6 times the recommended human dose based on body surface area) during organogenesis (day 6 to 18) inducing microphthalmia/small eye and/or focal retinal fold in 3 fetuses from 3 separate litters. in addition, multihance administered intravenously at 3 mmol/kg/day (10 times the recommended human dose based on body surface area) has been shown to increase intrauterine deaths in rabbits. there was no evidence that multihance induced teratogenic effects in rats at doses up to 2 mmol/kg/day (3 times the recommended human dose based on body surface area), however, rat dams exhibited no systemic toxicity at this dose. there were no adverse effects on the birth, survival, growth, development and fertility of the f1 generation at doses up to 2 mmol/kg in a rat peri- and post-natal (segment iii) study. risk summary limited literature reports that breastfeeding after gadobenate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001%-0.04% of the maternal dose. there is no information on the effects of the drug on the breastfed infant or the effects of the drug on milk production. additionally, there is limited gbca gastrointestinal absorption. the developmental and health benefits of breastfeeding should be considered together with the mother’s clinical need for multihance and any potential adverse effects on the breastfed infant from multihance or from the underlying maternal condition. multihance is approved for intravenous use for mri of the cns 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 less than 17 years of age. pediatric use is based on evidence of effectiveness in adults and in 202 pediatric patients 2 years of age and older, in addition to experience in 105 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 two years of age and older. for pediatric patients, less than 2 years of age, the recommended dosage range is 0.1 to 0.2 ml/kg [see dosage and administration (2.1), pharmacokinetics (12.3)] . the safety of multihance has not been established in preterm neonates. of the total number of 4967 adult subjects in clinical studies of multihance, 33% were 65 or older. no overall differences in safety or effectiveness were observed between these elderly subjects and the younger subjects. the drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to multihance 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.

Canada - engelsk - Health Canada

avir pharma inc. - gadopentetate dimeglumine - solution - 469mg - gadopentetate dimeglumine 469mg - miscellaneous therapeutic agents

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)].

Polen - polsk - URPL (Urząd Rejestracji Produktów Leczniczych, Wyrobów Medycznych i Produktów Biobójczych)

ge healthcare as - gadodiamidum - roztwór do wstrzykiwań - 0,5 mmol/ml

Brasil - portugisisk - ANVISA (Agência Nacional de Vigilância Sanitária)

ge healthcare do brasil comÉrcio e serviÇos para equipamentos medico-hospitalares ltda - gadodiamida - contrastes radiologicos

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

ge healthcare australia pty ltd - gadodiamide -

Spania - spansk - AEMPS (Agencia Española de Medicamentos y Productos Sanitarios)

ge healthcare bio-sciences, s.a.u. - gadodiamida - soluciÓn inyectable - 0,5 mmol/ml - gadodiamida 0,5 mmol - gadodiamida