Antineoplastic
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Moderate Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Potential Toxicity
PREGNANCY SUMMARY
No reports describing the use of porfimer in human pregnancy have been located. Although the dose comparisons used in the animal reproduction studies were based on body weight, there was no association with structural anomalies in two species at doses less than the human dose. Other aspects of developmental toxicity could not be assessed because the tested doses caused maternal toxicity. When the dose was decreased by 50% in one species and continued throughout lactation, there was a reduction in the body weights of the offspring. The absence of human pregnancy experience prevents a more complete assessment of the embryo–fetal risk. Nevertheless, if porfimer is required by a woman, the drug should not be withheld because of pregnancy. If inadvertent pregnancy does occur, the woman should be informed of the potential for embryo and fetal harm.
FETAL RISK SUMMARY
Porfimer is a mixture of oligomers formed by ether and ester linkages of up to eight porphyrin units. It is given IV as a photosensitizing agent used in photodynamic therapy. Photodynamic therapy with porfimer is indicated for cases of esophageal cancer, endobronchial non–small-cell lung cancer, and high-grade Barrett’s esophagus. In patients with cancer, the plasma elimination half-life was 250 ± 285 hours (about 10 ± 12 days), but in healthy volunteers, the half-life was 415 ± 104 hours (about 17 ± 4.3 days). Porfimer is about 90% protein bound in human serum.
Reproduction studies with porfimer have been conducted in rats and rabbits. In pregnant rats, an IV dose 0.64 times the human clinical dose based on BSA (HCD) given daily during organogenesis did not cause congenital malformations but did result in maternal and fetal toxicity (resorptions, decreased litter size, delayed ossification, and reduced fetal weight). An IV dose that was 0.32 times the HCD given daily to pregnant rats during late pregnancy through lactation caused a reversible decrease in growth of offspring. An IV dose 0.65 times the HCD, given daily to pregnant rabbits during organogenesis did not cause fetal anomalies, but did cause maternal toxicity resulting in resorptions, decreased litter size, and reduced fetal weight (1).
Long-term studies for carcinogenicity have not been conducted. Porfimer was not mutagenic or clastogenic in several tests. In studies with male and female rats, an IV dose 0.32 times the HCD caused no impairment of fertility. Long-term dosing resulted in discoloration of the testes and ovaries, hypertrophy of the testes, and decreased body weights (1).
It is not known if porfimer crosses the human placenta. Because it is a mixture of oligomers, the exact molecular weight, which is high, cannot be determined. The long elimination half-life, however, does increase the possibility that some may cross to the embryo or fetus.
BREASTFEEDING SUMMARY
No reports describing the use of porfimer during human lactation have been located.
Because it is a mixture of oligomers, the exact molecular weight, which is high, cannot be determined,. The long elimination half-life, however, does increase the possibility that some drug may be excreted into breast milk. The effect of this potential exposure on a nursing infant is unknown, but this agent is a photosensitizer.
Reference
1.Product information. Photofrin. Axcan Scandipharm, 2007.