Antifungal
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of caspofungin in human pregnancy have been located. A 2003 review of antifungal agents was also unable to find such reports (1). The animal data are suggestive of human risk, especially if exposure occurs in the 1st trimester. However, the absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. If indicated, maternal treatment should be avoided in the 1st trimester, if possible.
FETAL RISK SUMMARY
Caspofungin inhibits the synthesis of glucan, an integral component of the fungal cell wall, and is the first antifungal agent in this class. It is a semisynthetic lipopeptide (echinocandin) compound that is synthesized from a fermentation product of the fungus Glarea lozoyenis. Caspofungin is approved for the treatment of Candida infections and for invasive aspergillosis in patients who cannot be treated with other antifungals. Caspofungin is extensively bound to albumin (about 97%). Plasma clearance of caspofungin is primarily from distribution, rather than by excretion or by metabolism. The γ-phase half-life is 40–50 hours (2).
Reproduction studies have been conducted in rats and rabbits. In rats, doses producing exposures similar to those obtained in humans treated with a 70-mg dose (HE) were embryotoxic, resulting in increased resorptions and peri-implantation losses. Other effects included incomplete ossification of the skull and torso and an increased incidence of cervical ribs. The agent was also embryotoxic in rabbits, causing increased resorptions at doses similar to the HE. In addition, incomplete ossifications of the talus/calcaneus were observed in rabbits (2).
Caspofungin crosses the placenta in rats and rabbits (gestational age not specified) and the drug could be detected in fetal plasma (2). It is not known if the agent crosses the human placenta. The molecular weight (about 1213 for the acetate salt) and extensive plasma protein binding should limit the amount crossing the placenta, but the long β-phase half-life should provide substantial amounts of the drug available for transfer.
BREASTFEEDING SUMMARY
No reports describing the use of caspofungin during human lactation have been located. The high molecular weight (about 1213 for the acetate salt) and extensive plasma protein binding (about 97%) should limit the amount of drug excreted in breast milk, but the long γ-phase half-life may allow for some drug in the milk. The effect of this exposure on a nursing infant is unknown. However, other drugs from different classes of antifungal agents, such as fluconazole and ketoconazole, are classified as compatible with breastfeeding by the American Academy of Pediatrics (see Fluconazole and Ketoconazole). The risk of harm from exposure to caspofungin also appears to be low, and women being treated with caspofungin should be allowed to breastfeed. Their infants should be monitored for signs and symptoms of histamine release (e.g., rash, facial swelling, and pruritus) and gastrointestinal complaints.
References
1.Moudgal VV, Sobel JD. Antifungal drugs in pregnancy: a review. Expert Opin Drug Saf 2003;2:475–83.
2.Product information. Cancidas. Merck, 2004.