Ophthalmic Phototherapy
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: Limited Human Data—Potential Toxicity
PREGNANCY SUMMARY
Although the animal reproduction data suggest low risk, the near absence of human pregnancy experience prevents an assessment of the embryo–fetal risk. The human pregnancy experience is limited to three cases. Nevertheless, verteporfin is indicated for severe eye disease that might cause blindness if not treated. Therefore, if a pregnant woman requires verteporfin and she consents, treatment should not be withheld because of her pregnancy. Avoiding the period of organogenesis should be considered.
FETAL RISK SUMMARY
Verteporfin is a light-activated drug used in photodynamic therapy that is given by IV infusion. The drug then is activated in the eye with light from a nonthermal diode laser. Once activated in the presence of oxygen, highly reactive, short-lived singlet oxygen and reactive oxygen radicals are generated. Verteporfin is indicated for the treatment of patients with predominantly classic subfoveal choroidal neovascularization due to age-related macular degeneration, pathologic myopia, or presumed ocular histoplasmosis. Verteporfin undergoes limited metabolism by liver and plasma esterases. Excretion is by the fecal route. The elimination half-life of verteporfin is about 5–6 hours (1).
Reproduction studies have been performed in rats and rabbits. In pregnant rats during organogenesis, a dose resulting in exposures that were about 40 times the human exposure based on AUC (HE-AUC) caused an increased incidence of anophthalmia/microphthalmia in fetuses. At 125 times the HE-AUC, rat fetuses had an increased incidence of wavy ribs and anophthalmia/microphthalmia. In pregnant rabbits, no teratogenic effects were observed with doses that were not maternally toxic (1). Light activation was not mentioned in any of the above studies.
Carcinogenicity studies have not been conducted with verteporfin. Photodynamic therapy as a class has been reported to cause DNA damage that might result in chromosomal aberrations and mutations. It is not known how these effects translate into human risk (1). No effects on fertility were observed in male and female rats with doses that were about ≤60 and ≤40 times the HE-AUC, respectively (1).
It is not known if verteporfin crosses the human placenta. The molecular weight (about 719), limited metabolism, and the elimination half-life suggest that exposure of the embryo–fetus will occur.
A 2004 case report described the administration of verteporfin to a 35-year-old woman in the first week after conception of her first pregnancy (2). After counseling, the woman continued her pregnancy and delivered a healthy 2750-g female infant by cesarean section at 38 weeks’ gestation. Apgar scores were 9 and 10 at 1 and 5 minutes, respectively. The child was developing normally at 26 months of age (2).
A brief 2009 report described the use of verteporfin and bevacizumab in a pregnant woman treated for choroidal neovascularization secondary to punctate inner choroidopathy (3). She received photodynamic therapy with IV verteporfin about 1–2 weeks postconception. At 3 months postconception, she underwent intravitreal injection of 1.25 mg bevacizumab. The patient delivered a healthy infant at term with no evidence of congenital anomalies at birth or at 3 months of age (3).
In another 2009 report, a 45-year-old woman with choroidal neovascularization and an unknown pregnancy received fluorescein angiography at 9 weeks and verteporfin at 12 weeks (4). Pregnancy was diagnosed at about 25 weeks. At about 37 weeks, she gave birth spontaneously to a healthy 2410-g female infant without congenital anomalies and with Apgar scores of 9 and 10. The normal infant was doing well at 16 months of age (4).
BREASTFEEDING SUMMARY
Verteporfin and its diacid metabolite are excreted into human breast milk (1). After a 6 mg/m2 infusion, milk concentrations of the drug were 66% of the corresponding plasma concentration. Verteporfin was undetectable in milk after 12 hours, but the metabolite was measured in milk up to at least 48 hours (1). The excretion into milk is consistent with the molecular weight (about 719), limited metabolism, and elimination half-life (5–6 hours). The effect of this exposure on a nursing infant is unknown, but adverse effects affecting many organ systems are common in adults treated with IV infusions of the drug. Withholding breastfeeding for about 48 hours should lessen the exposure and potential risk of toxicity in the infant.
References
1.Product information. Visudyne. Novartis Pharmaceuticals, 2007.
2.De Santis M, Carducci B, De Santis L, Lucchese A, Straface G. First case of post-conception verteporfin exposure: pregnancy and neonatal outcome. Acta Ophthalmol Scand 2004;82:623–4.
3.Rosen E, Rubowitz A, Ferencz JR. Exposure to verteporfin and bevacizumab therapy for choroidal neovascularization secondary to punctate inner choroidopathy during pregnancy. Eye (Lond) 2009;23:1479.
4.Rodrigues M, Meira D, Batista S, Carrilho MM. Accidental pregnancy exposure to verteporfin: obstetrical and neonatal outcomes: a case report. Aust NZ J Obstet Gynaecol 2009;49:236–7.