Vitamin
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of paricalcitol in human pregnancy have been located. The drug did not cause structural anomalies in animals, but high doses did cause toxicity that was thought to be secondary to hypercalcemia. Human pregnancy experience with vitamin D and calcitriol indicates that recommended doses are safe in pregnancy. There is no evidence that the effects of recommended doses of paricalcitol would be any different. However, if the mother is taking paricalcitol, she should not take pharmacologic doses of vitamin D and its derivatives (1).
FETAL RISK SUMMARY
Paricalcitol is a synthetic analog of calcitriol, the physiologically active form of vitamin D. (See also Calcitriol and Vitamin D.) Paricalcitol, oral or IV, is indicated for the prevention and treatment of secondary hyperparathyroidism associated with chronic kidney disease. The vitamin is well absorbed (72%) and is extensively bound to plasma proteins (≥99.8%). Paricalcitol also is extensively metabolized. The plasma half-life in healthy individuals is 4–6 hours, but it is 17–20 hours in patients with chronic kidney disease (1).
Reproduction studies have been conducted in pregnant rabbits and rats. In these species, daily doses 0.5 and 2 times, respectively, the recommended human dose based on BSA (RHD) were associated with minimal decreases (5%) in fetal viability. In rats, a dose 13 times the RHD given 3 times weekly caused a significant increase in the mortality of newborn pups, but this dose also was maternally toxic. Long-term studies for carcinogenicity revealed an increased incidence of uterine leiomyoma and leiomyosarcoma in mice and uterine leiomyoma and benign adrenal pheochromocytoma in rats. Assays for mutagenic or clastogenic effects were negative, as was impairment of fertility in male and female rats (1).
Paricalcitol crosses the rat placenta (1), but studies in humans have not been located. The molecular weight (about 417) and the elimination half-life suggest that paricalcitol will cross to the embryo and fetus. Moreover, both vitamin D and calcitriol cross the human placenta (see Vitamin D) but do so slowly. Therefore, paricalcitol probably crosses placenta, but the extensive metabolism and plasma protein binding should limit the amount reaching the embryo and/or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of paricalcitol during human lactation have been located. The molecular weight (about 417) and the long elimination half-life in patients with chronic kidney disease (17–20 hours) suggest that the vitamin will be excreted into breast milk. However, the extensive metabolism and plasma protein binding should limit the amount in milk. Women who are nursing and taking paricalcitol should consider not taking vitamin supplements containing vitamin D. Whether such a woman does or does not, serum calcium levels in the nursing infant should be monitored.
Reference
1.Product information. Zemplar. Abbott Laboratories, 2006.