Diagnostic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Available 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). In addition, 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
Gadofosveset, 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 gadobenate dimeglumine, gadodiamide, gadopentetate dimeglumine, gadoteridol, and gadoversetamide. Gadofosveset trisodium is indicated for use as a contrast agent in magnetic resonance angiography (MRA) to evaluate aortoiliac occlusive disease in adults with known or suspected peripheral vascular disease. It binds reversibly to serum albumin, resulting in longer time in the vascular system than non-protein-binding contrast agents. Metabolism has not been detected and the mean elimination half-life is about 16 hours (6).
Reproduction studies have been conducted in rats and rabbits. In rats and rabbits, daily doses up to about 11 and 21.5 times, respectively, the human dose based on BSA (HD) did not cause fetal anomalies. In both species, the highest dose caused maternal toxicity. In rabbits, a daily dose 3 times the HD caused increased postimplantation loss, resorptions, and dead fetuses (6).
Long-term studies to evaluate the potential for carcinogenicity have not been conducted. Assays for mutagenicity and chromosome aberrations assay were negative. Male and female rat fertility was not impaired with daily doses up to 8.3 times the HD given for 4 and 2 weeks, respectively (6).
BREASTFEEDING SUMMARY
Although no reports describing the administration of gadofosveset during human lactation have been located, reviewers consider other gadolinium-based 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). However, gadofosveset has a much longer elimination half-life (16 hours) than other gadolinium-based contrast agents and, even though the agent is bound to albumin, the binding is reversible. Until human data are available, withholding breastfeeding for 24 hours or longer should lessen the amount available for excretion into breast milk.
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. Ablavar. Lantheus Medical Imaging, 2009.
7.Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 2001;106:776–89.