Included as part of the "PRECAUTIONS" Section
Intravenous administration of products containing benzyl alcohol has been associated with neonatal gasping syndrome consisting of severe metabolic acidosis, gasping respirations, progressive hypotension, seizures, central nervous system depression, intraventricular hemorrhage, and death in preterm, low birth weight infants. Neonates (i.e. patients less than 1 month of age or preterm infants with a corrected age of less than 44 weeks) could be at risk for gasping syndrome if treated with ULESFIA Lotion [see Use In Specific Populations].
Avoid eye exposure. ULESFIA Lotion may cause eye irritation. If ULESFIA Lotion comes in contact with the eyes, flush them immediately with water. If irritation persists, consult a physician.
ULESFIA Lotion may cause allergic or irritant dermatitis.
Use In Children
ULESFIA Lotion should only be used on children (6 months of age and older) under the direct supervision of an adult. Keep out of reach of children.
Patient Counseling Information
“See FDA-approved patient labeling (PATIENT INFORMATION)”
Inform the patient and caregiver of the following instructions:
- Apply ULESFIA Lotion for 10 minutes as directed in the ULESFIA Lotion Usage Guideline Table.
- Apply a second treatment 1 week (7 days) after the initial application.
- Use only on dry scalp and dry scalp hair.
- Avoid contact with eyes.
- ULESFIA Lotion may cause eye irritation, skin irritation, and contact sensitization.
- Wash hands after application.
- Report any signs of irritation at the application site and any signs of adverse reactions.
- Keep out of reach of children.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Long-term studies in animals have not been performed to evaluate the carcinogenic potential of ULESFIA Lotion. However, no evidence of carcinogenic activity was noted for benzyl alcohol in 2 year oral carcinogenicity studies in rats (doses up to 400 mg/kg benzyl alcohol) or mice (doses up to 200 mg/kg benzyl alcohol) conducted by the National Toxicology Program.
Benzyl alcohol has produced mixed results in genotoxicity tests. Benzyl alcohol was not mutagenic in the Ames test with and without metabolic activation, sex-linked recessive lethal assay, and a replicative DNA synthesis assay (conducted in male rats). Benzyl alcohol was negative in the mouse lymphoma assay with metabolic activation, but positive without metabolic activation at a concentration producing a high level of cellular toxicity. Benzyl alcohol was positive in the Chinese hamster ovary chromosomal aberration assay with metabolic activation.
No fertility studies have been conducted with benzyl alcohol.
Use In Specific Populations
Rare pregnancy outcomes reported in the published literature with benzyl alcohol use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Topical benzyl alcohol is unlikely to be absorbed through the skin in clinically relevant amounts; therefore, maternal use is not expected to result in fetal exposure to the drug.
In animal reproduction studies, subcutaneous administration of benzyl alcohol to pregnant rats and rabbits during organogenesis did not cause any malformations (see Data). The available data do not allow the calculation of relevant comparisons between the systemic exposure of benzyl alcohol observed in animal studies to the systemic exposure that would be expected in humans after topical use of ULESFIA Lotion.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively
In embryo-fetal development studies, pregnant rats and rabbits received subcutaneous doses of benzyl alcohol during organogenesis at doses up to 500 mg/kg/day and 400 mg/kg/day, respectively. There were no malformations noted in either species. In rats, maternal toxicity and decreased fetus weight occurred at 500 mg/kg/day. In rabbits, maternal toxicity occurred at 250 and 400 mg/kg/day and was associated with decreased fetal weight at 400 mg/kg/day.
There is no information available on the presence of benzyl alcohol in human or animal milk, the effects of the drug on breastfed infant, or the effects of the drug on milk production. When used as prescribed, topical benzyl alcohol is unlikely to be absorbed through the skin in clinically relevant amounts; therefore, breastfeeding is not expected to result in exposure of the infant to ULESFIA Lotion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ULESFIA Lotion and any potential adverse effects on the breastfed infant from ULESFIA Lotion or from the underlying maternal condition.
The safety and effectiveness of ULESFIA Lotion was evaluated in two multicenter, randomized, double-blind, vehicle-controlled studies which were conducted in 628 subjects 6 months of age and older with active head lice infestation [see Clinical Studies].
Rates of adverse events in younger children (6 months to 12 years) were similar to those of older children and adults.
Safety in pediatric patients below the age of 6 months has not been established. ULESFIA Lotion is not recommended in pediatric patients under six months of age because of the potential for increased systemic absorption due to a high ratio of skin surface area to body mass and the potential for an immature skin barrier.
Neonates could be at risk for gasping syndrome if treated with ULESFIA Lotion [see WARNINGS AND PRECAUTIONS].
Intravenous administration of products containing benzyl alcohol has been associated with neonatal gasping syndrome. The gasping syndrome (characterized by central nervous depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites found in the blood and urine) has been associated with benzyl alcohol dosages > 99 mg/kg/day in preterm neonates. Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hemotologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although expected systemic exposure of benzyl alcohol from proper use of ULESFIA Lotion is substantially lower than those reported in association with the gasping syndrome, the minimum amount of benzyl alcohol at which toxicity may occur is not known.
The safety of ULESFIA Lotion in patients over 60 years of age has not been established.