Hematological Agent (Kallikrein Inhibitor)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of ecallantide in human pregnancy have been located. The protein caused developmental toxicity (death) in one animal species, but the dose comparison was based on body weight, not BSA or AUC, and maternal toxicity was present. Although a rare genetic disorder, acute episodic attacks of hereditary angioedema can cause localized swelling, inflammation, and pain. If a pregnant woman requires ecallantide, consideration should be given to avoiding early gestation. She should be informed of the lack of human pregnancy experience and the potential risk of embryo death. Moreover, the woman should be informed of the risk of anaphylaxis that has occurred in 3.9% of treated patients (1).
FETAL RISK SUMMARY
Ecallantide, a small protein, is a human plasma kallikrein inhibitor. There are no other agents in this class. It is indicated for the treatment of acute attacks of hereditary angioedema in patients 16 years of age and older. After a single SC dose in healthy subjects, the mean elimination half-life was 2 hours. No information was provided for metabolism and plasma protein binding (1).
Reproduction studies have been conducted in rats and rabbits. In rats, an IV dose that was about 13 times the maximum recommended human dose (MRHD) based on body weight (MRHD-BW) caused increased numbers of early resorptions and percentages of resorbed conceptuses in the presence of mild maternal toxicity. No developmental toxicity was observed with IV doses that were about eight times the MRHD-BW. There were no adverse effects on rat embryo–fetal development with SC doses resulting in exposures up to about 2.4 times the MRHD based on AUC (MRHD-AUC). In rabbits, IV doses resulting in exposures up to about six times the MRHD-AUC were not associated with adverse effects on embryo–fetal development (1).
Studies for carcinogenic or mutagenic potential have not been conducted. SC doses up to about 21 times the MRHD-BW had no effect on fertility and reproductive performance in rats (1).
It is not known if ecallantide crosses the human placenta. The drug is a small protein with a molecular weight of 7054 and a short elimination half-life. These characteristics suggest that clinically significant amounts of the drug will not reach the embryo or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of ecallantide during human lactation have been located. The drug is a small protein with a molecular weight of 7054 and a short 2-hour elimination half-life. These characteristics suggest that clinically significant amounts of the drug will not be excreted into breast milk. The risks to a nursing infant from exposure to the protein appear to be low, if they exist at all.
Reference
1.Product information. Kalbitor. Dyaz, 2009.