Antifungal
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of anidulafungin in human pregnancy have been located. The animal reproduction data suggest low risk, but the absence of human pregnancy experience prevents a complete assessment of embryo–fetal risk. Moreover, there are no reports of human pregnancy experience with caspofungin and micafungin, the other agents in the class. Thus, the best course is to avoid anidulafungin in pregnancy, however, if the woman’s condition requires it, the benefit probably outweighs the unknown risk. The lowest possible dose should be used.
FETAL RISK SUMMARY
Anidulafungin is a semisynthetic lipopeptide antifungal agent administered by IV infusion. It is an echinocandin, a class of antifungal agents that also includes caspofungin and micafungin. Anidulafungin is indicated for the treatment of candidemia and other forms of Candida infections. Although it does not undergo hepatic metabolism, anidulafungin does undergo chemical degradation at physiologic temperature and pH to inactive peptidic compounds that are subsequently degraded and eliminated. The in vitro degradation half-life of the drug under physiologic conditions is about 24 hours. The terminal elimination half-life is 40–50 hours, with excretion primarily in the feces. Plasma protein binding of anidulafungin is moderate (84%) (1).
Reproduction studies have been conducted in rats and rabbits. In pregnant rats given a dose up two times the recommended human dose based on BSA (RHD), skeletal changes in rat fetuses were observed that included incomplete ossification of various bones and wavy, misaligned, or misshapen ribs. These effects, however, were not dose-related and were within the range of the laboratory’s historical control database. In pregnant rabbits, doses four times the RHD (the highest dose) were associated with slightly reduced fetal weights, but maternal toxicity was also noted (1).
Anidulafungin was not genotoxic in several tests. Carcinogenicity studies have not been conducted. There were no adverse effects on fertility from the drug in male and female rats given IV doses that were two times the RHD (1).
It is not known if anidulafungin can cross the human placenta. The molecular weight (about 1140) is high, but the long degradation half-life and moderate plasma protein binding suggest that transfer to the embryo and/or fetus might occur. Moreover, the recommended course of therapy involves daily IV doses for at least 14 days. Anidulafungin does cross the rat placenta and has been detected in fetal plasma (1).
BREASTFEEDING SUMMARY
No reports describing the use of anidulafungin during human lactation have been located.
The molecular weight (about 1140) is high, but the long degradation half-life and moderate plasma protein binding suggest that excretion into breast milk might occur. Moreover, the recommended course of therapy involves daily IV doses for at least 14 days. The effect on a nursing infant from potential exposure to the drug in milk is unknown. Dose-related histamine-mediated symptoms (rash, urticaria, flushing, pruritus, dyspnea, and hypotension) have been observed in adults receiving IV anidulafungin.
Reference
1.Product information. Eraxis. Pfizer, 2007.