These Highlights Do Not Include All The Information Needed To Use Eucrisa Safely And Effectively. See Full Prescribing Information For Eucrisa.

Risk Summary

Available data from case reports with EUCRISA use in pregnant women are insufficient to inform a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 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.

EUCRISA contains 2% crisaborole (w/w) in a petrolatum-based, white to off-white ointment and is for topical use. The active ingredient, crisaborole, is a phosphodiesterase-4 (PDE-4) inhibitor.

Crisaborole is described chemically as 5-(4-cyanophenoxy)-1,3-dihydro-1-hydroxy-[2,1]-benzoxaborole. The empirical formula is C₁₄H₁₀BNO₃ and the molecular weight is 251.1 g/mol.

The structural formula is represented below:

Crisaborole drug substance is freely soluble in common organic solvents such as isopropyl alcohol and propylene glycol, and insoluble in water.

Each gram of EUCRISA contains 20 mg of crisaborole in an ointment containing white petrolatum, propylene glycol, mono- and di-glycerides, paraffin, butylated hydroxytoluene, and edetate calcium disodium.

EUCRISA is a white to off-white ointment containing 2% crisaborole and is supplied in 60 g and 100 g laminate tubes.

60 g tube: NDC 55724-211-21

100 g tube: NDC 55724-211-11

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 administered twice daily in this age group is supported by data from two 28-day adequate, vehicle-controlled safety and efficacy trials (1,313 pediatric subjects ages 2 years to 17 years of whom 874 received EUCRISA), a 28-day open-label, safety and pharmacokinetics (PK) trial (137 subjects ages 3 months to less than 2 years who received EUCRISA), and another trial with an open-label period of up to 8 weeks (327 pediatric subjects ages 5 months to less than 18 years who received EUCRISA) [see 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.

Two multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials (Trials 1 and 2) treated a total of 1522 subjects 2 to 79 years of age (86.3% of subjects were 2 to 17 years of age) with a 5% to 95% treatable BSA. At baseline, 38.5% of the subjects had an Investigator's Static Global Assessment [ISGA] of mild (2), and 61.5% had an ISGA of moderate (3), in the overall assessment of atopic dermatitis (erythema, induration/papulation, and oozing/crusting) on a severity scale of 0 to 4.

In both trials, subjects were randomized 2:1 to receive EUCRISA or vehicle applied twice daily for 28 days. The primary efficacy endpoint was the proportion of subjects at Day 29 who achieved success, defined as an ISGA grade of clear (0) or almost clear (1) with a 2-grade or greater improvement from baseline, comparing EUCRISA-treated subjects to vehicle-treated subjects.

Efficacy results from the two trials are summarized in Table 2.

The success rates over time are presented in Figure 1.

One randomized, double-blind, vehicle-controlled trial (Trial 3) assessed the efficacy and safety of EUCRISA once daily over 52 weeks in pediatric (3 months to less than 18 years of age) and adult subjects with mild to moderate atopic dermatitis, who achieved success on EUCRISA twice daily during open-label treatment of up to 8 weeks.

A total of 497 subjects 3 months of age and older with a 2% to 90% treatable BSA, entered into an open-label period to receive EUCRISA twice daily for up to 8 weeks. At baseline, 327 (66%) of subjects were 3 months to less than 18 years of age, 66% of the subjects had an ISGA of moderate (3), and 34% had an ISGA of mild (2), in the overall assessment of atopic dermatitis (erythema, induration/papulation, and oozing/crusting) on a severity scale of 0 to 4.

Of the 497, a total of 254 subjects 3 months of age and older, who achieved both ISGA success (score of clear [0] or almost clear [1] with a ≥2 grade improvement from baseline) and EASI50 response (at least 50% improvement from baseline in EASI scores) were randomized 1:1 into a double-blind period to receive EUCRISA once daily or vehicle for 52 weeks or until they developed a flare. At the beginning of the double-blind period, 59% of the subjects had an ISGA of almost clear (1) and 41% had an ISGA of clear (0).

Figure 2 presents the percentage of subjects maintaining an ISGA of clear or almost clear through Week 52.

Figure 2: Percentage of Subjects Maintaining ISGA of Clear or Almost Clear Through Week 52

EUCRISA is contraindicated in patients with known hypersensitivity to crisaborole or any component of the formulation. [see Warnings and Precautions (5.1)]

The most common adverse reaction occurring in ≥1% in subjects is application site pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

EUCRISA is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older.

Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increased intracellular cyclic adenosine monophosphate (cAMP) levels. The specific mechanism(s) by which crisaborole exerts its therapeutic action for the treatment of atopic dermatitis is not well defined.

Store at 20°C–25°C (68°F–77°F); excursions permitted to 15°C–30°C (59°F–86°F).

[see USP Controlled Room Temperature].

Keep tube tightly closed.

Hypersensitivity reactions: If signs and symptoms of hypersensitivity occur, discontinue EUCRISA immediately and initiate appropriate therapy. (5.1)

Apply a thin layer of EUCRISA twice daily to affected areas. Once clinical effect is achieved, consider reducing application to once daily [see Clinical Studies (14) ].

EUCRISA is for topical use only and not for ophthalmic, oral, or intravaginal use.

Ointment: 20 mg of crisaborole per gram (2%) of white to off-white ointment.

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

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.

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

In one double-blind, vehicle-controlled trial including an initial open-label period (Trial 3), 497 subjects 3 months of age and older with mild to moderate atopic dermatitis received EUCRISA twice daily for up to 8 weeks. This was followed by a double-blind period, during which 135 subjects out of 270 randomized subjects received EUCRISA and 135 subjects received vehicle once daily for 52 weeks or until they developed a flare. The adverse reactions observed in the open-label period were similar to the known safety profile of twice daily treatment with EUCRISA. The adverse reactions observed with once daily treatment were similar to vehicle [see Clinical Studies (14)].

Advise the patient or caregivers to read the FDA-approved patient labeling (Patient Information).

eucrisa^®

(crisaborole) ointment 2%

NDC 55724-211-21

60 g

Rx only

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

eucrisa^®

(crisaborole) ointment 2%

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

NDC 55724-211-21

60 g

Rx only

eucrisa^®

(crisaborole) ointment 2%

PROFESSIONAL SAMPLE - NOT FOR SALE

NDC 55724-211-23

60 g

Rx only

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

eucrisa^®

(crisaborole) ointment 2%

PROFESSIONAL SAMPLE - NOT FOR SALE

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

NDC 55724-211-23

60 g

Rx only

In an oral carcinogenicity study in Sprague-Dawley rats, oral doses of 30, 100, or 300 mg/kg/day crisaborole were administered to rats once daily. A crisaborole-related increased incidence of benign granular cell tumors in the uterus with cervix and vagina (combined) was noted in 300 mg/kg/day crisaborole treated female rats (2 times the MRHD on an AUC comparison basis). The clinical relevance of this finding is unknown.

In a dermal carcinogenicity study in CD-1 mice, topical doses of 2%, 5%, or 7% crisaborole ointment were administered once daily. No crisaborole-related neoplastic findings were noted at topical doses up to 7% crisaborole ointment (1 times the MRHD on an AUC comparison basis).

Crisaborole revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (rat micronucleus assay).

No effects on fertility were observed in male or female rats that were administered oral doses up to 600 mg/kg/day crisaborole (13 times the MRHD on an AUC comparison basis) prior to and during early pregnancy.

Risk Summary

Available data from case reports with EUCRISA use in pregnant women are insufficient to inform a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. 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.

EUCRISA contains 2% crisaborole (w/w) in a petrolatum-based, white to off-white ointment and is for topical use. The active ingredient, crisaborole, is a phosphodiesterase-4 (PDE-4) inhibitor.

Crisaborole is described chemically as 5-(4-cyanophenoxy)-1,3-dihydro-1-hydroxy-[2,1]-benzoxaborole. The empirical formula is C₁₄H₁₀BNO₃ and the molecular weight is 251.1 g/mol.

The structural formula is represented below:

Crisaborole drug substance is freely soluble in common organic solvents such as isopropyl alcohol and propylene glycol, and insoluble in water.

Each gram of EUCRISA contains 20 mg of crisaborole in an ointment containing white petrolatum, propylene glycol, mono- and di-glycerides, paraffin, butylated hydroxytoluene, and edetate calcium disodium.

EUCRISA is a white to off-white ointment containing 2% crisaborole and is supplied in 60 g and 100 g laminate tubes.

60 g tube: NDC 55724-211-21

100 g tube: NDC 55724-211-11

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 administered twice daily in this age group is supported by data from two 28-day adequate, vehicle-controlled safety and efficacy trials (1,313 pediatric subjects ages 2 years to 17 years of whom 874 received EUCRISA), a 28-day open-label, safety and pharmacokinetics (PK) trial (137 subjects ages 3 months to less than 2 years who received EUCRISA), and another trial with an open-label period of up to 8 weeks (327 pediatric subjects ages 5 months to less than 18 years who received EUCRISA) [see 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.

Two multicenter, randomized, double-blind, parallel-group, vehicle-controlled trials (Trials 1 and 2) treated a total of 1522 subjects 2 to 79 years of age (86.3% of subjects were 2 to 17 years of age) with a 5% to 95% treatable BSA. At baseline, 38.5% of the subjects had an Investigator's Static Global Assessment [ISGA] of mild (2), and 61.5% had an ISGA of moderate (3), in the overall assessment of atopic dermatitis (erythema, induration/papulation, and oozing/crusting) on a severity scale of 0 to 4.

In both trials, subjects were randomized 2:1 to receive EUCRISA or vehicle applied twice daily for 28 days. The primary efficacy endpoint was the proportion of subjects at Day 29 who achieved success, defined as an ISGA grade of clear (0) or almost clear (1) with a 2-grade or greater improvement from baseline, comparing EUCRISA-treated subjects to vehicle-treated subjects.

Efficacy results from the two trials are summarized in Table 2.

The success rates over time are presented in Figure 1.

One randomized, double-blind, vehicle-controlled trial (Trial 3) assessed the efficacy and safety of EUCRISA once daily over 52 weeks in pediatric (3 months to less than 18 years of age) and adult subjects with mild to moderate atopic dermatitis, who achieved success on EUCRISA twice daily during open-label treatment of up to 8 weeks.

A total of 497 subjects 3 months of age and older with a 2% to 90% treatable BSA, entered into an open-label period to receive EUCRISA twice daily for up to 8 weeks. At baseline, 327 (66%) of subjects were 3 months to less than 18 years of age, 66% of the subjects had an ISGA of moderate (3), and 34% had an ISGA of mild (2), in the overall assessment of atopic dermatitis (erythema, induration/papulation, and oozing/crusting) on a severity scale of 0 to 4.

Of the 497, a total of 254 subjects 3 months of age and older, who achieved both ISGA success (score of clear [0] or almost clear [1] with a ≥2 grade improvement from baseline) and EASI50 response (at least 50% improvement from baseline in EASI scores) were randomized 1:1 into a double-blind period to receive EUCRISA once daily or vehicle for 52 weeks or until they developed a flare. At the beginning of the double-blind period, 59% of the subjects had an ISGA of almost clear (1) and 41% had an ISGA of clear (0).

Figure 2 presents the percentage of subjects maintaining an ISGA of clear or almost clear through Week 52.

Figure 2: Percentage of Subjects Maintaining ISGA of Clear or Almost Clear Through Week 52

EUCRISA is contraindicated in patients with known hypersensitivity to crisaborole or any component of the formulation. [see Warnings and Precautions (5.1)]

The most common adverse reaction occurring in ≥1% in subjects is application site pain. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

EUCRISA is indicated for topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients 3 months of age and older.

Crisaborole is a phosphodiesterase 4 (PDE-4) inhibitor. PDE-4 inhibition results in increased intracellular cyclic adenosine monophosphate (cAMP) levels. The specific mechanism(s) by which crisaborole exerts its therapeutic action for the treatment of atopic dermatitis is not well defined.

Store at 20°C–25°C (68°F–77°F); excursions permitted to 15°C–30°C (59°F–86°F).

[see USP Controlled Room Temperature].

Keep tube tightly closed.

Hypersensitivity reactions: If signs and symptoms of hypersensitivity occur, discontinue EUCRISA immediately and initiate appropriate therapy. (5.1)

Apply a thin layer of EUCRISA twice daily to affected areas. Once clinical effect is achieved, consider reducing application to once daily [see Clinical Studies (14) ].

EUCRISA is for topical use only and not for ophthalmic, oral, or intravaginal use.

Ointment: 20 mg of crisaborole per gram (2%) of white to off-white ointment.

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

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.

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

In one double-blind, vehicle-controlled trial including an initial open-label period (Trial 3), 497 subjects 3 months of age and older with mild to moderate atopic dermatitis received EUCRISA twice daily for up to 8 weeks. This was followed by a double-blind period, during which 135 subjects out of 270 randomized subjects received EUCRISA and 135 subjects received vehicle once daily for 52 weeks or until they developed a flare. The adverse reactions observed in the open-label period were similar to the known safety profile of twice daily treatment with EUCRISA. The adverse reactions observed with once daily treatment were similar to vehicle [see Clinical Studies (14)].

Advise the patient or caregivers to read the FDA-approved patient labeling (Patient Information).

eucrisa^®

(crisaborole) ointment 2%

NDC 55724-211-21

60 g

Rx only

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

eucrisa^®

(crisaborole) ointment 2%

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

NDC 55724-211-21

60 g

Rx only

eucrisa^®

(crisaborole) ointment 2%

PROFESSIONAL SAMPLE - NOT FOR SALE

NDC 55724-211-23

60 g

Rx only

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

eucrisa^®

(crisaborole) ointment 2%

PROFESSIONAL SAMPLE - NOT FOR SALE

For Topical Use Only.

Not for ophthalmic, oral, or intravaginal use.

NDC 55724-211-23

60 g

Rx only

In an oral carcinogenicity study in Sprague-Dawley rats, oral doses of 30, 100, or 300 mg/kg/day crisaborole were administered to rats once daily. A crisaborole-related increased incidence of benign granular cell tumors in the uterus with cervix and vagina (combined) was noted in 300 mg/kg/day crisaborole treated female rats (2 times the MRHD on an AUC comparison basis). The clinical relevance of this finding is unknown.

In a dermal carcinogenicity study in CD-1 mice, topical doses of 2%, 5%, or 7% crisaborole ointment were administered once daily. No crisaborole-related neoplastic findings were noted at topical doses up to 7% crisaborole ointment (1 times the MRHD on an AUC comparison basis).

Crisaborole revealed no evidence of mutagenic or clastogenic potential based on the results of two in vitro genotoxicity tests (Ames assay and human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (rat micronucleus assay).

No effects on fertility were observed in male or female rats that were administered oral doses up to 600 mg/kg/day crisaborole (13 times the MRHD on an AUC comparison basis) prior to and during early pregnancy.