Antidote/Chelating Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
Three reports describing the use of deferasirox in human pregnancy have been located (1–3). Doses that were very low in comparison with the human dose were used in the animal studies, presumably because higher doses were maternally toxic. The lack of fetal harm in these studies suggests that the risk in human pregnancy is low, but the limited human pregnancy experience prevents a more complete assessment. Another iron-chelating agent, deferoxamine, has been used in pregnancy without any evidence of fetal toxicity (see Deferoxamine).
FETAL RISK SUMMARY
Deferasirox is an oral iron-chelating agent indicated for the treatment of chronic iron overload due to blood transfusions. Although the affinity for zinc and copper is much lower, deferasirox also may lower serum concentrations of these metals. The absolute oral bioavailability is 70%, and the drug accumulates after multiple doses. Protein binding, almost exclusively to albumin, is very high (99%). Elimination of deferasirox and its metabolites is primarily by excretion in the feces, with an elimination half-life of 8–16 hours (4).
Reproduction studies have been conducted in rats and rabbits. No evidence of impaired fertility or fetal harm was observed in these species with oral doses up to about 0.8 times the recommended human dose based on BSA (RHD). No effects on fertility and reproductive performance were observed in male and female rats at doses up to about 0.6 times the RHD. Studies for carcinogenicity and mutagenicity also were negative (4).
It is not known if deferasirox crosses the human placenta. The molecular weight (about 373) and long elimination half-life suggest that exposure of the embryo and/or fetus will occur, but the very high protein binding should limit the exposure.
Three case reports have described the use of deferasirox in pregnant women with thalassemia (1–3). In each case, the drug was started before conception and continued until pregnancy was diagnosed at 22, 20, and 12 weeks’. No abnormalities related to the exposure were observed in the normal newborns (1–3).
BREASTFEEDING SUMMARY
No reports describing the use of deferasirox during human lactation have been located. The molecular weight (about 373) and long elimination half-life (8–16 hours) suggest that the drug will be excreted into breast milk. The amount of oral absorption in an infant is unknown. However, in adults, the absolute oral bioavailability is 70%, and the drug accumulates after multiple doses (4). The recommended therapy with deferasirox is very long (months), and such therapy during breastfeeding might deplete the infant’s iron stores. Therefore, if the mother is taking deferasirox, the safest course is not to breastfeed.
References
1.Vini D, Servos P, Drosou M. Normal pregnancy in a patient with β-thalassaemia major receiving iron chelation therapy with deferasirox (Exjade). Eur J Haematol 2011;86:274–5.
2.Anastasi S, Lisi R, Abbate G, Caruso V, Giovannini M, De Sanctis V. Absence of teratogenicity of deferasirox treatment during pregnancy in a thalassaemic patient. Pediatr Endocrinol Rev 2011;8(Suppl 2):345–7.
3.Ricchi P, Costantini S, Spasiano A, Di Matola T, Cinque P, Prossomariti L. A case of well-tolerated and safe deferasirox administration during the first trimester of a spontaneous pregnancy in advanced maternal age thalassemic patient. Acta Haematol 2011;125:222–4.
4.Product information. Exjade. Novartis Pharmaceutical, 2005.