EUCRISA

1 Pediatrics Pediatrics (3 months to <18 years): Based on the data submitted and reviewed by Health Canada, the safety and effectiveness of EUCRISA have been established in pediatric patients age 3 months and older for topical treatment of mild to moderate atopic dermatitis.

Pediatrics (<3 months of age):

No data are available to Health Canada, therefore, Health Canada has not authorized an indication for pediatric patients below the age of 3 months. 2 Geriatrics Geriatrics (≥ 65 years of age): Evidence from clinical studies of EUCRISA did not include sufficient numbers of patients 65 years of age and over to determine whether they respond differently from younger patients.

2 CONTRAINDICATIONS EUCRISA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see

1 Adverse Reaction Overview The most common adverse drug reactions reported in clinical trials among patients with mild to moderate atopic dermatitis 2 years of age and older have been application site reactions. 2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions.

The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.

EUCRISATM (Crisaborole Ointment) Page 7 of 21 In two randomized, double-blind, parallel-group, vehicle-controlled Phase 3 clinical trials (Studies AN2728-AD-301 and AN2728-AD-302), 1012 patients 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 patients is listed in Table 2. 20%) a Refers to skin sensations such as burning or stinging. In one double-blind, vehicle-controlled, maintenance trial (C3291035), 497 subjects 5 months to 79 years of age with mild to moderate atopic dermatitis entered into an open-label period and were first treated with EUCRISA twice daily for up to 8 weeks.

The adverse reactions observed in the open-label period were consistent with the known safety profile of twice daily EUCRISA. During the double-blind maintenance period, 135 subjects out of 270 randomized subjects were treated with EUCRISA and 135 subjects received vehicle once daily for 52 weeks or until they developed a flare.

The adverse reactions observed with once daily EUCRISA treatment were similar to vehicle. 1 Clinical Trial Adverse Reactions – Pediatrics In a multicenter, open-label, uncontrolled trial, 137 pediatric subjects aged 3 months to less than 2 years were treated with EUCRISA twice daily for 4 weeks.

Hypersensitivity 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. 1 Pregnant Women 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 Route of Administration Dosage Form / Strength/Composition Non-medicinal Ingredients Topical Ointment 20 mg of crisaborole per gram (2%) of white to off- white ointment butylated hydroxytoluene, edetate calcium disodium, mono- and di-glycerides, paraffin, white petrolatum, propylene glycol.

EUCRISATM (Crisaborole Ointment) Page 6 of 21 during organogenesis at doses up to 3 and 2 times, respectively, the maximum recommended human dose (MRHD). 2 Breast-feeding It is unknown if EUCRISA is excreted in human milk. There is no information available on the effects of the drug on the breastfed infant or the effects 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.

Because many drugs are excreted in human milk, precaution should be exercised. 3 Pediatrics Pediatrics (3 months to <18 years): Based on the data submitted and reviewed by Health Canada, the safety and effectiveness of EUCRISA for topical treatment of mild to moderate atopic dermatitis have been established in pediatric patients age 3 months and older.

EUCRISA is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.