Ophthalmic
PREGNANCY RECOMMENDATION: No Human Data—Probably Compatible
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of pegaptanib in human pregnancy have been located. The animal data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment. However, the very low plasma levels probably prevent clinically significant amounts of the drug from reaching the embryo or fetus. Thus, if a woman requires pegaptanib, it should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Pegaptanib is an aptamer—a pegylated modified oligonucleotide that is a selective vascular endothelial growth factor (VEGF) antagonist. It is in the same class as ranibizumab. Pegaptanib is indicated for the treatment of neovascular (wet) age-related macular degeneration. It is administered as a 0.3-mg intravitreous injection every 6 weeks. When a 3-mg dose (10 times the recommended dose) was given, the mean maximum plasma concentration, about 80 ng/mL, occurred within 1–4 days. The mean AUC was about 25 mcg·hr/mL and the plasma elimination half-life was about 10 days. Pegaptanib is metabolized but the amount of metabolism apparently has not been determined (1).
Reproduction studies have been conducted in mice. In pregnant mice, no evidence of maternal toxicity, teratogenicity, or fetal mortality was observed with daily IV doses up to about 7000 times the recommended human monocular ophthalmic dose of 0.3 mg based on body weight (1).
Studies for carcinogenicity and fertility have not been conducted with pegaptanib. Mutagenicity and clastogenicity assays with pegaptanib and its monomer component nucleotides have been negative (1).
It is not known if pegaptanib crosses the human placenta. The molecular weight (about 50,000) suggests that exposure of the embryo and/or fetus is unlikely. The drug does cross the mouse placenta after IV administration (1). Moreover, the plasma elimination half-life is very long. Nevertheless, if the drug does cross the human placenta, the very low plasma levels will limit the amount reaching the embryo and/or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of pegaptanib during human lactation have been located. Although the long plasma elimination half-life (about 10 days) favors excretion, the molecular weight (about 50,000) and very low plasma concentrations suggest that the drug will not be excreted into breast milk. The effects of any exposure on a nursing infant are unknown, but probably are clinically insignificant. Thus, if a lactating woman requires pegaptanib, it should not be withheld because she is breastfeeding.
Reference
1.Product information. Macugen. Eyetech Pharmaceuticals, 2006.