Tsjekkia - tsjekkisk - SUKL (Státní ústav pro kontrolu léčiv)

guerbet, roissy cdg cedex array - 10803 kyselina gadoterovÁ - injekční roztok v předplněné injekční stříkačce - 279,32mg/ml - kyselina gadoterovÁ

Tsjekkia - tsjekkisk - SUKL (Státní ústav pro kontrolu léčiv)

guerbet, roissy cdg cedex array - 10803 kyselina gadoterovÁ - injekční roztok - 279,32mg/ml - kyselina gadoterovÁ

USA - engelsk - NLM (National Library of Medicine)

guerbet llc - gadoterate meglumine (unii: l0nd3981ag) (gadolinium cation (3+) - unii:azv954tz9n) - gadolinium cation (3+) 376.9 mg in 1 ml - dotarem 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 dotarem [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 dotarem 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 on 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 breast-fed 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 dotarem and any potential adverse effects on the breastfed infant from dotarem 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 dotarem 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 dotarem has not been established in preterm neonates. no cases of nsf associated with dotarem or any other gbca have been identified in pediatric patients age 6 years and younger [see warnings and precautions (5.2)] . normal estimated gfr (egfr) is approximately 30 ml/minute/1.73m2 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 dotarem, 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 dotarem 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 dotarem dosage adjustment is recommended for patients with renal impairment. gadoterate 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)

guerbet llc - gadoterate meglumine (unii: l0nd3981ag) (gadolinium cation (3+) - unii:azv954tz9n) - dotarem 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 dotarem [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 dotarem 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 levels 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 or 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 breast-fed infant. gadoterate is present in goat milk (see data) . the developmental and health benefits of breastfeeding should be considered along with the mother’s clnical need for dotarem and any potential adverse effects on the breastfed infant from dotarem 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 dotarem 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 dotarem has not been established in preterm neonates. no cases of nsf associated with dotarem or any other gbca have been identified in pediatric patients age 6 years and younger [see warnings and precautions (5.2)] . normal estimated gfr (egfr) is approximately 30 ml/minute/1.73m2 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 dotarem, 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 dotarem 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 dotarem dosage adjustment is recommended for patients with renal impairment. gadoterate can be removed from the body by hemodialysis [ see warnings and precautions (5.2) and clinical pharmacology (12.3) ].

Frankrike - fransk - ANSM (Agence Nationale de Sécurité du Médicament et des Produits de Santé)

guerbet - acide gadotérique 27 - solution - 27,932 g - pour 100 ml de solution > acide gadotérique 27,932 g sous forme de : dota 20,246 g et sous forme de : oxyde de gadolinium 9,062 g - produit de contraste paramagnétique pour irm - dotarem est un produit à usage diagnostique. il appartient au groupe des produits de contraste utilisés en imagerie par résonance magnétique (irm).ce médicament est à usage diagnostique uniquement.dotarem est administré afin d’améliorer le contraste des images obtenues lors d’un examen par irm. ceci facilite la visualisation et la délimitation de certaines parties du corps.

Frankrike - fransk - ANSM (Agence Nationale de Sécurité du Médicament et des Produits de Santé)

guerbet - acide gadotérique 27 - solution - 27,932 g - pour 100 ml de solution > acide gadotérique 27,932 g sous forme de : oxyde de gadolinium 9,062 g et sous forme de : dota 20,246 g - produit de contraste paramagnétique pour irm - dotarem est un produit à usage diagnostique. il appartient au groupe des produits de contraste utilisés en imagerie par résonance magnétique (irm).ce médicament est à usage diagnostique uniquement.dotarem est administré afin d’améliorer le contraste des images obtenues lors d’un examen par irm. ceci facilite la visualisation et la délimitation de certaines parties du corps.

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

guerbet australia pty ltd - gadoteric acid, quantity: 279.32 mg/ml - injection, solution - excipient ingredients: meglumine; water for injections - dotarem is indicated, in adults and children, for use with magnetic resonance imaging to provide contrast enhancement for intracranial and spinal lesions with abnormal blood brain barrier or abnormal vascularity, and for whole body imaging (see clinical studies).

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

guerbet australia pty ltd - gadoteric acid, quantity: 279.32 mg/ml - injection, solution - excipient ingredients: meglumine; water for injections - dotarem is indicated, in adults and children, for use with magnetic resonance imaging to provide contrast enhancement for intracranial and spinal lesions with abnormal blood brain barrier or abnormal vascularity, and for whole body imaging (see clinical studies).

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

guerbet australia pty ltd - gadoteric acid, quantity: 279.32 mg/ml - injection, solution - excipient ingredients: meglumine; water for injections - dotarem is indicated, in adults and children, for use with magnetic resonance imaging to provide contrast enhancement for intracranial and spinal lesions with abnormal blood brain barrier or abnormal vascularity, and for whole body imaging (see clinical studies).

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

guerbet australia pty ltd - gadoteric acid, quantity: 279.3 mg/ml - injection, solution - excipient ingredients: meglumine; water for injections - dotarem is indicated, in adults and children, for use in magnetic resonance imaging to provide contrast enhancement for intracranial and spinal lesions with abnormal brain barrier or abnormal vascularity, and for whole body imaging (see clinical studies).