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.
Gadopentetate dimeglumine was administered intravenously during organogenesis at doses of at 0.25, 0.75, and 1.25 mmol/kg/day for 10 consecutive days in pregnant rats and for 13 consecutive days in pregnant rabbits. Gadopentetate dimeglumine caused retardation of fetal development at a dose of 1.25 mmol per kg (rats) and 0.75 mmol per kg (rabbits); 2 times and 2.4 times, respectively, the recommended human dose (based on BSA).
Gadopentetate dimeglumine was not teratogenic in pregnant rats and rabbits when given repeatedly during organogenesis at a dose of 3 mmol per kg in rabbits and 4.5 mmol per kg in rats; 9.7 times and 7.3 times, respectively, the recommended human dose (based on BSA).
Limited literature reports that breastfeeding after gadopentetate dimeglumine administration to the mother would result in the infant receiving an oral dose of 0.001 to 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 along with the mother’s clinical need for Magnevist and any potential adverse effects on the breastfed child from Magnevist or from the underlying maternal condition.
Intravenous injections of gadopentetate dimeglumine (16 to 18 doses over 23 to 25 days) caused spermatogenic cell atrophy and degeneration that was irreversible in male rats at a dose of 8 times (based on BSA) the recommended human dose [see Nonclinical Toxicology (13.1)].
The use of Magnevist in imaging the central nervous system, extracranial/extraspinal tissues, and body have been established in the pediatric population from the ages of 2 to 16 years on the basis of adequate and well controlled clinical trials in adults and safety studies in this pediatric population [see Clinical Studies (14)].
Safety and efficacy in the pediatric population under the age of 2 years have not been established. Magnevist is eliminated primarily by the kidney. In a study with pediatric patients aged 2 months to < 2 years the pharmacokinetics (body weight-normalized clearance, body weight-normalized distribution volume, and terminal half-life) of gadopentetate were similar to adults.
Systemic consequences associated with overdosage of Magnevist injection have not been reported.
Magnevist® (brand of gadopentetate dimeglumine) injection is the N-methylglucamine salt of the gadolinium complex of diethylenetriamine pentaacetic acid, and is an injectable contrast medium for magnetic resonance imaging (MRI). Magnevist Injection is provided as a sterile, clear, colorless to slightly yellow aqueous solution for intravenous injection.
Magnevist Injection is a 0.5-mol/L solution of 1-deoxy-1-(methylamino)-D-glucitol dihydrogen [N,N-bis[2-[bis(carboxymethyl)amino]ethyl] glycinato (5-) ]gadolinate(2-)(2:1) with a molecular weight of 938, an empirical formula of C28 H54 GdN5 O20 , and has the following structural formula:
Each mL of Magnevist injection contains 469.01 mg gadopentetate dimeglumine, 0.99 mg meglumine, 0.40 mg diethylenetriamine pentaacetic acid, and water for injection. Magnevist injection contains no antimicrobial preservative.
Magnevist Injection has a pH of 6.5 to 8.0. Pertinent physicochemical data are noted below:
at 37° C
at 20° C
at 37° C
at 25° C
at 25° C
Octanol: H2 O Coefficient
at 25° C, pH7 log Pow = — 5.4
Magnevist injection has an osmolality 6.9 times that of plasma, which has an osmolality of 285 mOsmol/kg water. Magnevist injection is hypertonic under conditions of use.
Magnevist is a paramagnetic agent and, as such, it develops a magnetic moment when placed in a magnetic field. The relatively large magnetic moment produced by the paramagnetic agent results in a relatively large local magnetic field, which can enhance the relaxation rates of water protons in the vicinity of the paramagnetic agent.
In magnetic resonance imaging (MRI), visualization of normal and pathological brain tissue depends in part on variations in the radiofrequency signal intensity that occur with 1) changes in proton density; 2) alteration of the spin-lattice or longitudinal relaxation time (T1); and 3) variation of the spin-spin or transverse relaxation time (T2). When placed in a magnetic field, gadopentetate dimeglumine decreases the T1 and T2 relaxation time in tissues where it accumulates. At usual doses, the effect is primarily on the T1 relaxation time.
Disruption of the blood-brain barrier or abnormal vascularity allows accumulation of gadopentetate dimeglumine in lesions such as neoplasms, abscesses, and subacute infarcts. The pharmacokinetic parameters of Magnevist in various lesions are not known.
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