EUCRISA Ointment Ref.[10069] Active ingredients: Crisaborole

5.1 Hypersensitivity Reactions

Hypersensitivity reactions, including contact urticaria, have occurred in patients treated with EUCRISA. Hypersensitivity should be suspected in the event of severe pruritus, swelling and erythema at the application site or at a distant site. If signs and symptoms of hypersensitivity occur, discontinue EUCRISA immediately and initiate appropriate therapy.

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 practice.

In two double-blind, vehicle-controlled clinical trials (Trial 1 and Trial 2), 1012 subjects 2 to 79 years of age with mild to moderate atopic dermatitis were treated with EUCRISA twice daily for 4 weeks. The adverse reaction reported by ≥1% of EUCRISA-treated subjects is listed in Table 1.

Table 1. Adverse Reaction Occurring in ≥1% of Subjects in Atopic Dermatitis Trials through Week 4:

* Refers to skin sensations such as burning or stinging.

Less common (<1%) adverse reactions in subjects treated with EUCRISA included contact urticaria [see Warnings and Precautions (5.1)].

The following adverse reactions have been identified during postapproval use of EUCRISA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:

Skin and Subcutaneous: allergic contact dermatitis.

Risk Summary

There is no available data with EUCRISA in pregnant women to inform the drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of crisaborole in pregnant rats and rabbits during organogenesis at doses up to 3 and 2 times, respectively, the maximum recommended human dose (MRHD) [see Data].

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies carry some risk of birth defect, loss, or other adverse outcomes. The background risk of major birth defects in the U.S. general population is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data

Animal Data

Rat and rabbit embryo-fetal development was assessed after oral administration of crisaborole. Crisaborole did not cause adverse effects to the fetus at oral doses up to 300 mg/kg/day in pregnant rats during the period of organogenesis (3 times the MRHD on an area under the curve (AUC) comparison basis). No crisaborole-related fetal malformations were noted after oral treatment with crisaborole in pregnant rats at doses up to 600 mg/kg/day (13 times the MRHD on an AUC comparison basis) during the period of organogenesis. Maternal toxicity was produced at this high dose of 600 mg/kg/day in pregnant rats and was associated with decreased fetal body weight and delayed skeletal ossification. Crisaborole did not cause adverse effects to the fetus at oral doses up to the highest dose tested of 100 mg/kg/day in pregnant rabbits during the period of organogenesis (2 times the MRHD on an AUC comparison basis).

In a prenatal/postnatal development study, pregnant rats were treated with crisaborole at doses of 150, 300, or 600 mg/kg/day by oral gavage during gestation and lactation (from gestation day 7 through day 20 of lactation). Crisaborole did not have any adverse effects on fetal development at doses up to 300 mg/kg/day (3 times the MRHD on an AUC comparison basis). Maternal toxicity was produced at the high dose of 600 mg/kg/day in pregnant rats and was associated with stillbirths, pup mortality, and reduced pup weights.

Risk Summary

There is no information available on the presence of EUCRISA in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production after topical application of EUCRISA to women who are breastfeeding. EUCRISA is systemically absorbed. The lack of clinical data during lactation precludes a clear determination of the risk of EUCRISA to a breastfed infant. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EUCRISA and any potential adverse effects on the breastfed infant from EUCRISA or from the underlying maternal condition.

The safety and effectiveness of EUCRISA have been established in pediatric patients ages 3 months and older for topical treatment of mild to moderate atopic dermatitis. Use of EUCRISA in this age group is supported by data from two 28-day adequate, vehicle-controlled safety and efficacy trials which included 1,313 pediatric subjects ages 2 years to 17 years of whom 874 received EUCRISA. The most commonly reported adverse reaction in subjects 2 years and older was application site pain. Additionally, use of EUCRISA in pediatric patients ages 3 months to less than 2 years was supported by data from a 28-day open-label, safety and pharmacokinetics (PK) trial in 137 subjects. No new safety signals were identified in subjects 3 months to less than 2 years of age [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].

The safety and effectiveness of EUCRISA in pediatric patients below the age of 3 months have not been established.

Clinical studies of EUCRISA did not include sufficient numbers of subjects age 65 and over to determine whether they respond differently from younger subjects.