Hematologic (Hematopoietic)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of plerixafor during human pregnancy have been located. The animal reproduction data suggest risk but only one species was studied. If a pregnant woman’s disease requires the use of this agent, she should be informed of the potential risk to her embryo or fetus.
FETAL RISK SUMMARY
Plerixafor, a hematopoietic stem cell mobilizer, is an inhibitor of the CXCR4 chemokine receptor and blocks binding of its cognate ligand, stromal cell-derived factor-1α. It is indicated in combination with granulocyte-colony stimulating factor to mobilize hematopoietic stem cells to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma and multiple myeloma. Plerixafor is not metabolized. Plasma protein binding is up to 58% and the terminal half-life is 3–5 hours in patients with normal renal function (1).
Reproduction studies have been conducted in rats. In this species, embryo–fetal toxicity was observed mainly at a dose that was about 10 times the recommended human dose of 0.24 mg/kg based on BSA or 10 times the AUC in subjects with normal renal function who received a single of 0.24 mg/kg. The embryo–fetal toxicities included fetal death, increased resorptions and postimplantation loss, decreased fetal weights, anophthalmia, shortened digits, cardiac interventricular septal defect, ringed aorta, globular heart, hydrocephaly, dilation of olfactory ventricles, and retarded skeletal development (1).
Carcinogenicity studies have not been conducted with plerixafor. The drug was not genotoxic in various assays. Studies in animals on male or female fertility have not been conducted. However, no adverse effects were observed on spermatogenesis in rats in a 28-day repeated dose toxicity study, nor was there any evidence of toxicity in male or female reproductive organs (1).
It is not known if plerixafor crosses the human placenta. However, the molecular weight (about 503), lack of metabolism, moderate plasma protein binding, and moderately long terminal half-life suggest that the drug will cross to the embryo or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of plerixafor during human lactation have been located. The molecular weight (about 503), lack of metabolism, moderate plasma protein binding (up to 58%), and moderately long terminal half-life (3–5 hours) suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown. The safest course for the infant would be to hold nursing for about 24 hours after a dose. If the mother is given this drug and continues nursing, her infant should be closely monitored for the most common adverse reactions seen in adults: diarrhea, nausea, fatigue, headache, arthralgia, dizziness, and vomiting.
Reference
1.Product information. Mozobil. Genzyme, 2010.