ULESFIA Lotion Ref.[9951] Active ingredients: Benzyl alcohol

5.1 Neonatal Toxicity

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 (8.4].

5.2 Eye Irritation

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.

5.3 Contact Dermatitis

ULESFIA Lotion may cause allergic or irritant dermatitis.

5.4 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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The rates of adverse reactions below were derived from two randomized, multi-center, vehicle-controlled clinical trials and one open-label study in subjects with head lice infestation.

Skin, scalp, and ocular irritation were monitored in the clinical trials. All subjects were queried about the presence of skin and scalp symptoms; the results are presented in Table 2.

Table 2. Monitored Adverse Reactions – Application Site Symptoms:

The subset of subjects who did not have pruritus, erythema, edema or pyoderma of skin and scalp, or ocular irritation prior to treatment were assessed for these signs and symptoms after treatment; the results are presented in Table 3.

Table 3. Monitored Adverse Reactions – Pruritus, Erythema, Pyoderma and Ocular Irritation with Onset After Treatment:

Other less common reactions (less than 1% but more than 0.1%) were, in decreasing order of incidence: application site dryness, application site excoriation, paraesthesia, application site dermatitis, excoriation, thermal burn, dandruff, erythema, rash, and skin exfoliation.

Drug interaction studies were not conducted with ULESFIA Lotion.

Pregnancy Category B.

There are no adequate and well-controlled studies with topical benzyl alcohol in pregnant women. Reproduction studies conducted in rats and rabbits were negative. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

No comparisons of animal exposure with human exposure are provided in this labeling due to the low systemic exposure noted in the clinical pharmacokinetic study [see Clinical Pharmacology (12.3] which did not allow for the determination of human AUC values that could be used for this calculation.

Pregnant rats were dosed with benzyl alcohol via subcutaneous injection at 100, 250, and 500 mg/kg/day. No teratogenic effects were noted at any dose. Maternal toxicity and decreased fetal weight occurred at 500 mg/kg/day. When pregnant rabbits received subcutaneous injections of benzyl alcohol at 100, 250, and 400 mg/kg/day, there were no teratogenic effects in offspring at any dose. In rabbits, maternal toxicity occurred at the two higher doses and was associated with decreased fetal weight at the highest dose.

It is not known whether benzyl alcohol is excreted into human milk. Because some systemic absorption of topical benzyl alcohol may occur and because many drugs are excreted in human milk, caution should be exercised when ULESFIA Lotion is administered to a nursing woman.

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 (14)].

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 (5.1)].

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.