Pediculicide/Anti-infective
PREGNANCY RECOMMENDATION: Limited Human Data—Probably Compatible (Topical) Contraindicated (Injectable)
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible (Topical) Contraindicated (Injectable)
PREGNANCY SUMMARY
Benzyl alcohol is used topically for head lice and as a bacteriostatic preservative in injectable solutions and other drug formulations. The animal reproduction data suggest low risk, but there is only one report describing its use as a preservative in a drug during human pregnancy and none as a pediculicide. Although a dose–response relationship has not been established, it is doubtful if sufficient benzyl alcohol would be absorbed from topical application to cause embryo–fetal toxicity. Thus, the embryo–fetal risk from topical use appears to be low, if it exists at all. The embryo–fetal risk from benzyl alcohol-preserved injectable products given to a pregnant woman is unknown. However, the plasma concentrations of the agent will be much higher than that obtained from topical use, so the safest course is to avoid injectable products, especially IV fluids, containing benzyl alcohol during pregnancy.
FETAL RISK SUMMARY
Benzyl alcohol is a pediculicide that is available as a 5% lotion. It is also used as a preservative in some injectable fluids and in multidose vials. As a lotion, it is indicated for the topical treatment of head lice infestation in patients 6 months of age and older. Treatment is repeated in 7 days. Small amounts of the drug were absorbed in 4 of 19 subjects when an exaggerated exposure period (3 times the normal exposure period) was used. Plasma concentrations in three subjects (6 months–3 years age group) at 0.5 hour posttreatment were 1.97–2.99 mcg/mL, whereas one subject in the 4–11 year age group 1 hour after treatment had a concentration of 1.63 mcg/mL (1). Benzyl alcohol is rapidly oxidized to benzoic acid and then conjugated in the liver with glycine to form hippuric acid (2). No information on the plasma protein binding, pKa, or elimination half-life has been located.
Comparisons between animal and human exposures could not be conducted because of the low systemic exposures in humans. Consequently, SC injections were given to pregnant rats and rabbits in doses that were 100–500 and 100–400 mg/kg, respectively. No teratogenic effects were noted in either species, but maternal toxicity was observed at the highest doses.
The carcinogenic potential of the lotion in animals has not been evaluated. However, no evidence of carcinogenic activity was observed in oral 2-year high dose studies in rats and mice. Mutagenic studies have revealed positive and negative findings. Fertility studies have not been conducted (1).
It is not known if benzyl alcohol crosses the human placenta. The molecular weight (about 108) is low enough, but the plasma concentrations are very low even after a higher than normal exposure period with the lotion.
A 1977 report described a postpartum woman with severe flaccid paraplegia that was thought to be due to benzyl alcohol. One hour after delivery, normal saline (40 mL) containing 1.5% benzyl alcohol as a preservative had been inadvertently injected into an epidural catheter. The neurologic symptoms gradually improved over the next 16 months (3).
Beginning in pregnancy, a 22-year-old woman who was homozygous for factor V Leiden was treated with dalteparin injections from a multidose vial that contained benzyl alcohol (4). In the fifth month of pregnancy, the physician became aware of the exposure and changed to a dalteparin formulation without the preservative. No toxicity was observed and 4 months later the woman gave birth to a healthy infant (no other details provided) (4).
BREASTFEEDING SUMMARY
No reports describing exposure to benzyl alcohol during lactation have been located. The molecular weight (about 108) is low enough for excretion into milk, but the plasma concentrations after topical use of the lotion are very low, if at all. Higher plasma concentrations should be expected if the mother has an IV catheter requiring flushes with benzyl alcohol preserved fluids or is receiving injections from multidose vials containing the preservative. Premature infants and term neonates typically have immature liver function and may not be able to conjugate benzoic acid, the initial metabolite, to hippuric acid, resulting in metabolic acidosis (2). However, although a dose–response relationship has not been determined, it appears unlikely that a nursing infant’s exposure to benzyl alcohol from breast milk would be high enough to cause toxicity.
References
1.Product information. Ulesfia. Shionogi Pharma, 2010.
2.Centers for Disease Control and Prevention. Neonatal deaths associated with use of benzyl alcohol—United States. MMWR 1982;31:290–1.
3.Craig DB, Habib GG. Flaccid paraparesis following obstetrical epidural anesthesia: possible role of benzyl alcohol. Anesth Analg 1977;56:219–21.
4.Moll S. A low-molecular-weight heparin preparation contraindicated during pregnancy. Am J Obstet Gynecol 2001;184:1046.