Diagnostic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Probably Compatible
PREGNANCY SUMMARY
Gadolinium-based contrast agents are complexes with chelating agents that lower the potential toxicity in patients receiving the agents by preventing the cellular uptake of free gadolinium. The complexes cross the placenta to the fetus and are excreted by the fetal kidneys into the amniotic fluid, where they remain for long periods. The complexes themselves are relatively nontoxic, but dissociation may occur to release free gadolinium into the amniotic fluid where it could expose fetal lungs and gut. Presently, the risk of gadolinium-induced toxicity in the fetus is unknown but may be harmful (1–3). A concern has been raised for a risk of gadolinium-induced nephrogenic systemic fibrosis (3). The American College of Radiology recommends that these agents should not be routinely used in pregnancy and, if such use is indicated, a written informed consent be obtained from the patient (1). The guidelines of the Contrast Media Safety Committee of the European Society of Urogenital Radiology and a review article recommend that gadolinium-based contrast media may be used in pregnancy if such use is important to the mother’s health (4,5).
FETAL RISK SUMMARY
Gadobenate dimeglumine, a paramagnetic agent, is a complex formed between a chelating agent and a paramagnetic ion, gadolinium. It is in the same subclass of gadolinium-based contrast agents as gadodiamide, gadofosveset trisodium, gadopentetate dimeglumine, gadoteridol, and gadoversetamide. Gadobenate dimeglumine is given IV for magnetic resonance imaging (MRI) of the central nervous system in adults. Neither metabolism nor plasma protein binding of the agent has been detected. The mean elimination half-life is about 1–2 hours (6).
Reproduction studies have been conducted in rats and rabbits. In rats, no evidence of teratogenicity, other developmental toxicities (i.e., birth, survival, growth, development, and fertility of the next generation), or maternal toxicity at a daily IV dose that was three times the human dose based on BSA (HD). Teratogenicity (microphthalmia/small eye and/or focal retinal fold in three fetuses from three litters) was observed in rabbits given a daily IV dose during organogenesis that was six times the HD. A dose that was 10 times the HD resulted in increased intrauterine deaths (6).
Long-term studies to evaluate the potential for carcinogenicity have not been conducted. Assays for mutagenicity and chromosome aberrations assay were negative. No effect on male and female rat fertility was observed with daily IV doses up to three times the HD. A dose five times the HD caused irreversible toxicity in male rat reproductive organs. These effects were not observed in dog and monkey studies with doses up to about 11 and 10 times, respectively, the HD (6).
BREASTFEEDING SUMMARY
Although no reports describing the administration of gadobenate dimeglumine during human lactation have been located, reviewers consider gadolinium contrast media to be compatible with breastfeeding because of the very small amounts excreted into milk and potentially being absorbed by a nursing infant (2–4). The American Academy of Pediatrics classifies gadopentetate dimeglumine as compatible with breastfeeding (7) (see Gadopentetate Dimeglumine).
References
1.Kanal E, Barkovich AJ, Bell C, Borgstede JP, Bradley WG Jr, Froelich JW, Gilk T, Gimbel JR, Gosbee J, Kuhni-Kaminski E, Lester JW Jr, Nyenhuis J, Parag Y, Schaefer DJ, Sebek-Scoumis EA, Weinreb J, Zaremba LA, Wilcox P, Lucey L, Sass N, for the ACR Blue Ribbon Panel on MR Safety. ACR guidance document for safe MR practices: 2007. AJR Am J Roentgenol 2007;188:1447–74.
2.Lin SP, Brown JJ. MR contrast agents: physical and pharmacologic basics. J Magn Reson Imaging 2007;25:884–99.
3.Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol 2008;112:333–40.
4.Webb JAW, Thomsen HS, Morcos SK, and members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). The use of iodinated and gadolinium contrast media during pregnancy and lactation. Eur Radiol 2005;15:1234–40.
5.Garcia-Bournissen F, Shrim A, Koren G. Safety of gadolinium during pregnancy. Can Fam Physician 2006;52:309–10.
6.Product information. Multihance. Bracco Diagnostics, 2007.
7.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;106:776–89.