Antidote (Phosphate Binder)
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of lanthanum carbonate in human pregnancy have been located. The indication for the drug suggests that human pregnancy experience will be very limited. The systemic bioavailability is minimal and should have no effect on the embryo or fetus.
FETAL RISK SUMMARY
Lanthanum carbonate, an oral phosphate binder, is indicated to reduce serum phosphate in patients with end-stage renal disease. In the acid environment of the upper gastrointestinal tract, lanthanum ions are released to bind dietary phosphate from food during digestion. The resulting lanthanum phosphate complexes are highly insoluble. The systemic bioavailability of lanthanum carbonate is very low (<0.002%) with a mean plasma concentration of 0.6 ng/mL. The drug is practically insoluble in water. Lanthanum carbonate is not metabolized. Plasma protein binding is >99% and the plasma elimination half-life is 53 hours. However, lanthanum is bound to bone and is slowly released with an estimated half-life of 2.0–3.6 years (1).
Reproduction studies have been conducted in rats and rabbits. In rats, oral doses up to 3.4 times the maximum recommended daily human dose (MRDHD) resulted in no evidence of fetal harm. When the highest dose was given from implantation through lactation, offspring had delayed eye opening, reduction in body weight gain, and delayed sexual development (preputial separation and vaginal opening). In rabbits, doses up to 5 times the MRDHD were maternal toxic (reduced body weight gain and food consumption) and were associated with increased postimplantation loss, reduced fetal weights, and delayed fetal ossification (1).
In long-term studies, lanthanum carbonate was not carcinogenic in rats but was associated with an increased incidence of glandular stomach adenomas in male mice. The drug did not cause mutagenicity or chromosomal aberrations in multiple tests. Fertility of male and female rats was not affected by doses up to 3.4 times the MRDHD (1).
It is not known if lanthanum carbonate crosses the human placenta. The molecular weight (about 458 for anhydrous form) is low enough, but the very low systemic bioavailability and high plasma protein binding suggest that exposure of the embryo–fetus will not be clinically significant.
BREASTFEEDING SUMMARY
No reports describing the use of lanthanum carbonate during human lactation have been located. The very low systemic bioavailability (<0.002%) and high plasma protein binding (>99%) suggest that insignificant amounts of the drug will be excreted into breast milk. Moreover, even the minimal amounts that might be excreted would bind with milk phosphate, resulting in a nonabsorbable complex. The effect of this binding on infant bone growth is unknown but is probably not clinically significant.
Reference
1.Product information. Fosrenol. Shire US Manufacturing, 2009.