Risk Factor: B
Class: Diagnostic agents
Fetal Risk Summary
The diagnostic agent, fluorescein sodium (Dye and Coloring Yellow No. 8), is available as a topical solution, dye-impregnated paper strips, and as a solution for IV injection. No adverse fetal effects were observed in the offspring of pregnant albino rats administered IV sodium fluorescein (10%) at a dose of 5 mL/kg (1). The agent crossed the placenta and distributed throughout the fetuses within 15 minutes. Using phenobarbital in mature rats exposed in utero to multiple maternal IV doses of 10% sodium fluorescein, the investigators determined that in utero exposure to the dye had no effect on their drug detoxification systems later in life (1). No adverse effects on fetal development were observed when pregnant rats and rabbits were treated by gavage with multiple high doses (up to 1500 mg/kg in rats and up to 250 mg/kg in rabbits) of sodium fluorescein during organogenesis (2). Similarly, no adverse fetal outcomes occurred when pregnant rabbits were administered multiple 1.4-mL IV doses of 10% sodium fluorescein during the first two-thirds of gestation (3).
No reports describing the use of fluorescein sodium during human pregnancy have been located. Use of the topical solution in the eye (as well as IV injection) produces measurable concentrations of the dye in the systemic circulation (see Reference # 6) and passage to the fetus should be expected.
Breast Feeding Summary
Fluorescein sodium is excreted into human breast milk (4,5). A 29-year-old woman, who suffered acute central vision loss shortly after premature delivery of twins, was administered a 5-mL IV dose of 10% fluorescein sodium for diagnostic angiography (4). Her hospitalized infants were not fed her milk because of concern that the fluorescein in the milk could cause a phototoxic reaction if consumed (a severe bullous skin eruption was observed in a premature infant receiving phototherapy for hyperbilirubinemia shortly after administration of IV fluorescein angiography ). Milk concentrations of the dye were measured in seven samples collected between 6 and 76 hours after fluorescein administration. The highest and lowest concentrations, 372 ng/mL and 170 ng/mL, were measured at 6 and 76 hours, respectively. The elimination half-life of fluorescein in the woman’s milk was approximately 62 hours (4).
In a second case, a 28-year-old woman, 3 months postpartum, was administered a topical 2% solution in both eyes (6). Her infant was not allowed to breast-feed on the day of instillation. Absorption into the systemic circulation was documented with plasma fluorescein concentrations of 36 and 40 ng/mL at 45 and 75 minutes, respectively, after the dose. Milk concentrations at 30, 60, and 90 minutes were 20, 22, and 15 ng/mL, respectively. Because of these data, the authors recommended that mothers should not breast-feed for 812 hours after fluorescein topical administration.
The two mothers in the above cases either did not breast feed or temporarily withheld nursing to allow the dye to clear from their milk because of concerns for a fluorescein-induced phototoxic reaction in their infants. Although the American Academy of Pediatrics considers topical fluorescein to be compatible with breast feeding (7), the much higher milk concentrations obtained following IV fluorescein indicate that a risk may exist, especially in those infants undergoing phototherapy, and feeding should be temporarily withheld (8).
- Salem H, Loux JJ, Smith S, Nichols, CW. Evaluation of the toxicologic and teratogenic potentials of sodium fluorescein in the rat. Toxicology 1979;12:14350.
- Burnett CM, Goldenthal EI. The teratogenic potential in rats and rabbits of D and C Yellow no. 8. Food Chem Toxicol 1986;24:81923.
- McEnerney JK, Wong WP, Peyman GA. Evaluation of the teratogenicity of fluorescein sodium. Am J Ophthalmol 1977;84:84750.
- Maguire AM, Bennett J. Fluorescein elimination in human breast milk. Arch Ophthalmol 1986;106:7189.
- Kearns GL, Williams BJ, Timmons OD. Fluorescein phototoxicity in a premature infant. J Pediatr 1985;107:7968.
- Mattern J, Mayer PR. Excretion of fluorescein into breast milk. Am J Ophthalmol 1990;109:5989.
- Committee on Drugs, American Academy of Pediatrics. The transfer of drugs and other chemicals into human milk. Pediatrics 1994;93:13750.
- Anderson PO. Medication use while breast feeding a neonate. Neonatal Pharmacol Q 1993;2:314.