Antineoplastic
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 aldesleukin in human pregnancy have been located. The limited animal reproduction data, although based on body weight and at doses causing maternal toxicity, suggest low risk. In addition, the biologic effects of aldesleukin are the same as endogenous interleukin-2. Nevertheless, until human pregnancy experience is available, the best course is to avoid use of this agent in pregnancy. However, metastatic renal carcinoma and melanoma are potentially fatal, so if a woman requires aldesleukin and informed consent is obtained, it should not be withheld because of pregnancy. If an inadvertent pregnancy occurs, the woman should be advised of the unknown risk to her embryo–fetus.
FETAL RISK SUMMARY
Aldesleukin, a biologic response modifier, is a human recombinant interleukin product produced by recombinant technology. The protein possesses the biologic activities of human native interleukin-2. Aldesleukin is in the same antineoplastic subclass as denileukin. Aldesleukin is indicated for the treatment of metastatic renal carcinoma and metastatic melanoma. After IV infusion, aldesleukin undergoes rapid distribution into the extravascular space and elimination by metabolism. The distribution and elimination half-lives are 13 and 85 minutes, respectively (1).
In a reproduction study in rats, embryolethal effects were observed at IV doses that were 27–36 times the human dose based on body weight (HD). However, IV doses 2.1–36 times higher than the HD caused significant maternal toxicity. No evidence of teratogenicity other than that caused by maternal toxicity was observed. Studies for carcinogenicity, mutagenicity, or effects on fertility have not been conducted (1).
It is not known if aldesleukin crosses the human placenta. The molecular weight of the protein, about 15,300, suggests that it does not. However, other proteins, such as the immunoglobulins cross the placenta. Moreover, the protein rapidly distributes into tissues (e.g., into the lung, liver, kidney, and spleen in rats). The very short distribution and elimination half-lives may limit the amount reaching the embryo and fetus.
BREASTFEEDING SUMMARY
No reports describing the use of aldesleukin during human lactation have been located.
The molecular weight, about 15,300, suggests that it will not be excreted into breast milk. However, other proteins, such as the immunoglobulins, are excreted into milk and so may aldesleukin. The very short distribution (13 minutes) and elimination (85 minutes) half-lives may limit the amount reaching the embryo and fetus. Waiting about 4 hours after a dose to breastfeed should limit the potential exposure of the infant even more. The effects, if any, on a nursing infant are unknown.
Reference
1.Product information. Proleukin. Novartis Pharmaceuticals, 2007.