Eucrisa

Description

EUCRISA contains 2% crisaborole (w/w) in a petrolatum-based, white to off-white ointment intended for topical use. The active ingredient, crisaborole, is a phosphodiesterase-4 (PDE-4) inhibitor. Chemically, crisaborole is identified as 5-(4-cyanophenoxy)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole, with an empirical formula of C14H10BNO3 and a molecular weight of 251.1 g/mol. The drug substance is freely soluble in common organic solvents such as isopropyl alcohol and propylene glycol, but is insoluble in water. Each gram of EUCRISA contains 20 mg of crisaborole, along with inactive ingredients including white petrolatum, propylene glycol, mono- and di-glycerides, paraffin, butylated hydroxytoluene, and edetate calcium disodium.

Uses and Indications

EUCRISA is a phosphodiesterase 4 inhibitor indicated for the topical treatment of mild to moderate atopic dermatitis in adult and pediatric patients aged 3 months and older.

There are no teratogenic or nonteratogenic effects associated with the use of EUCRISA.

Dosage and Administration

Healthcare professionals are advised to apply a thin layer of the medication to the affected areas twice daily. Upon achieving the desired clinical effect, it may be appropriate to reduce the frequency of application to once daily. This medication is intended for topical use only and should not be applied to the eyes, taken orally, or used intravaginally.

Contraindications

Use of this product is contraindicated in patients with known hypersensitivity to crisaborole or any component of the formulation. This contraindication is based on the potential for severe allergic reactions in susceptible individuals.

Warnings and Precautions

Hypersensitivity reactions have been reported in patients using EUCRISA. In the event that signs and symptoms of hypersensitivity occur, it is imperative to discontinue the use of EUCRISA immediately and initiate appropriate therapeutic measures to manage the reaction.

Currently, there are no additional general precautions or laboratory tests specified for the safe use of EUCRISA. Healthcare professionals should remain vigilant for any adverse reactions and ensure that patients are monitored accordingly.

Side Effects

Patients may experience a range of adverse reactions while using crisaborole. The most common adverse reaction reported is application site pain, which occurs in 1% or more of subjects.

Hypersensitivity reactions have been noted; if any signs or symptoms of hypersensitivity occur, it is imperative to discontinue EUCRISA immediately and initiate appropriate therapy. Patients with a known hypersensitivity to crisaborole or any component of the formulation should not use this medication.

In clinical studies, no crisaborole-related neoplastic findings were observed at topical doses up to 7% in a dermal carcinogenicity study. However, an increased incidence of benign granular cell tumors in the uterus, cervix, and vagina was noted in female rats treated with 300 mg/kg/day of crisaborole in an oral carcinogenicity study. The clinical relevance of this finding remains unknown.

Furthermore, crisaborole has demonstrated no evidence of mutagenic or clastogenic potential based on genotoxicity tests. Additionally, no effects on fertility were observed in male or female rats administered oral doses up to 600 mg/kg/day of crisaborole prior to and during early pregnancy.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there are no known interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are necessary at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Eucrisa (crisaborole), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of EUCRISA have been established in pediatric patients aged 3 months and older for the topical treatment of mild to moderate atopic dermatitis. In this age group, EUCRISA is administered twice daily, with support from data derived from several clinical trials.

Two 28-day, adequate, vehicle-controlled trials included 1,313 pediatric subjects aged 2 years to 17 years, of whom 874 received EUCRISA. Additionally, a 28-day open-label safety and pharmacokinetics trial involved 137 subjects aged 3 months to less than 2 years who received EUCRISA. Another trial featured an open-label period of up to 8 weeks, encompassing 327 pediatric subjects aged 5 months to less than 18 years who received EUCRISA.

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

Geriatric Use

Clinical studies of EUCRISA did not include a sufficient number of subjects aged 65 and over to determine whether elderly patients respond differently from younger patients. Therefore, the safety and efficacy of EUCRISA in geriatric patients have not been established.

Healthcare providers should exercise caution when prescribing EUCRISA to elderly patients, considering the potential for altered pharmacokinetics and increased sensitivity to treatment. Monitoring for adverse effects and therapeutic response is recommended in this population. Additionally, dosage adjustments may be necessary based on individual patient factors, including comorbidities and concurrent medications.

Pregnancy

Available data from case reports regarding the use of EUCRISA (crisaborole) in pregnant women are insufficient to establish a drug-associated risk for major birth defects, miscarriage, or other adverse maternal or fetal outcomes. The background risk of major birth defects and miscarriage in the indicated population remains unknown, although it is acknowledged that all pregnancies carry some risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the background risk of major birth defects is estimated to be between 2% to 4%, while the risk of miscarriage is approximately 15% to 20% of clinically recognized pregnancies.

Animal reproduction studies have shown no adverse developmental effects associated with oral administration of crisaborole in pregnant rats and rabbits during organogenesis at doses up to 3 and 2 times the maximum recommended human dose (MRHD), respectively. Specifically, crisaborole did not cause adverse effects to the fetus at oral doses up to 300 mg/kg/day in pregnant rats during organogenesis, which corresponds to 3 times the MRHD based on area under the curve (AUC) comparisons. Furthermore, no fetal malformations were noted in pregnant rats treated with doses up to 600 mg/kg/day (13 times the MRHD on an AUC basis) during the same period. However, maternal toxicity was observed at this high dose, leading to decreased fetal body weight and delayed skeletal ossification.

In pregnant rabbits, crisaborole did not produce adverse effects on fetal development at doses up to 100 mg/kg/day (2 times the MRHD on an AUC basis) during organogenesis. Additionally, in a prenatal/postnatal development study, no adverse effects were noted at doses up to 300 mg/kg/day (3 times the MRHD on an AUC basis). It is important to note that maternal toxicity was observed at the high dose of 600 mg/kg/day in pregnant rats, which was associated with stillbirths, pup mortality, and reduced pup weights.

Healthcare professionals should consider these findings when prescribing crisaborole to pregnant patients and weigh the potential benefits against the unknown risks associated with its use during pregnancy.

Lactation

There is no information available on the presence of EUCRISA in human milk, nor on the effects of the drug on breastfed infants or on milk production following topical application in lactating mothers. EUCRISA is systemically absorbed, but the lack of clinical data during lactation precludes a clear determination of the risk to a breastfed infant.

Therefore, the developmental and health benefits of breastfeeding should be weighed against the mother's clinical need for EUCRISA and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition.

Renal Impairment

There is no information available regarding renal impairment, dosage adjustments, special monitoring, or safety considerations for patients with reduced kidney function. Healthcare professionals should exercise caution and consider individual patient factors when treating patients with renal impairment, as specific guidelines or recommendations are not provided in the current data.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there is no information available regarding dosage adjustments, special monitoring requirements, or precautions for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population.

Overdosage

In the absence of specific overdosage information, it is essential for healthcare professionals to remain vigilant regarding the potential risks associated with excessive administration of the medication.

In the event of suspected overdosage, it is recommended that healthcare providers assess the patient's clinical status and consider the following general management procedures:

1. Assessment of Symptoms: Healthcare professionals should monitor for any unusual or severe symptoms that may arise, which could indicate an adverse reaction to the medication. Symptoms may vary depending on the drug's pharmacological profile and the patient's individual response.

2. Supportive Care: Supportive measures should be initiated as necessary. This may include maintaining airway patency, providing supplemental oxygen, and ensuring adequate circulation.

3. Contact Poison Control: In cases of suspected overdosage, it is advisable to contact a poison control center or a medical toxicologist for guidance on specific management strategies tailored to the medication involved.

4. Consideration of Antidotes: If applicable, healthcare professionals should be aware of any available antidotes or specific treatments that may mitigate the effects of the overdosage.

5. Documentation and Reporting: It is crucial to document the incident thoroughly and report it to the appropriate regulatory authorities as required.

Healthcare professionals are encouraged to consult the product's prescribing information for any additional guidance on managing overdosage and to remain informed about the latest clinical recommendations.

Nonclinical Toxicology

In an oral carcinogenicity study conducted in Sprague-Dawley rats, oral doses of 30, 100, or 300 mg/kg/day of crisaborole were administered once daily. An increased incidence of benign granular cell tumors in the uterus, cervix, and vagina (combined) was observed in female rats treated with 300 mg/kg/day of crisaborole, which corresponds to two times the maximum recommended human dose (MRHD) based on area under the curve (AUC) comparison. The clinical relevance of this finding remains unknown.

In a dermal carcinogenicity study involving CD-1 mice, topical doses of 2%, 5%, or 7% crisaborole ointment were applied once daily. No neoplastic findings related to crisaborole were noted at topical doses up to 7%, which is equivalent to one times the MRHD based on AUC comparison.

Crisaborole demonstrated no evidence of mutagenic or clastogenic potential, as indicated by the results of two in vitro genotoxicity tests (the Ames assay and the human lymphocyte chromosomal aberration assay) and one in vivo genotoxicity test (the rat micronucleus assay).

No effects on fertility were observed in male or female rats administered oral doses of crisaborole up to 600 mg/kg/day, which is 13 times the MRHD based on AUC comparison, prior to and during early pregnancy.

Postmarketing Experience

Postmarketing experience has identified that EUCRISA may lead to allergic reactions, which can occur at or near the application site or at distant sites. These reactions may be serious and include symptoms such as difficulty breathing, throat tightness, hives, chest tightness, itching, feelings of faintness, redness, and swelling of the face, eyelids, lips, mouth, tongue, or throat. In the event of any allergic reaction symptoms, it is advised to discontinue use of EUCRISA and seek immediate medical assistance.

Additionally, application site pain, including sensations of burning or stinging, has been reported as the most common side effect associated with EUCRISA. It is important to note that these are not the only potential side effects of the medication. Patients are encouraged to consult their healthcare provider for medical advice regarding side effects and may report any adverse events to the FDA at 1-800-FDA-1088.

Patient Counseling

Advise patients or their caregivers to read the FDA-approved patient labeling (Patient Information) thoroughly. It is essential to inform patients that EUCRISA is intended for topical use only and should not be applied to the eyes, mouth, or vagina. Patients must discontinue the use of EUCRISA and seek immediate medical attention if they experience any signs or symptoms of hypersensitivity.

Patients should be cautioned against using EUCRISA if they are allergic to crisaborole or any of its ingredients. Prior to using EUCRISA, patients must inform their healthcare provider about all existing medical conditions, particularly if they are pregnant or planning to become pregnant, as the effects of EUCRISA on an unborn baby are not known. Additionally, patients who are breastfeeding or plan to breastfeed should discuss this with their healthcare provider, as it is unclear whether EUCRISA passes into breast milk.

It is important for patients to disclose all medications they are currently taking, including prescription and over-the-counter drugs, vitamins, and herbal supplements. Patients should use EUCRISA exactly as directed by their healthcare provider, typically applying a thin layer to the affected areas twice daily or as instructed. After application, patients should wash their hands unless they are treating their hands. If someone else is applying EUCRISA on behalf of the patient, they should also wash their hands afterward.

Patients should be aware that EUCRISA may cause allergic reactions, which can be serious. They must stop using the medication and seek medical help immediately if they experience symptoms such as difficulty breathing, throat tightness, hives, chest tightness, itching, feeling faint, or swelling of the face, eyelids, lips, mouth, tongue, or throat. The most common side effect reported is application site pain, including burning or stinging sensations.

Patients are encouraged to contact their healthcare provider for medical advice regarding any side effects and may report side effects to the FDA at 1-800-FDA-1088. EUCRISA should be stored at room temperature, between 68°F to 77°F (20°C to 25°C), with the tube kept tightly closed. It is crucial to keep EUCRISA and all medications out of the reach of children and to avoid using EUCRISA for any condition other than that for which it was prescribed. Patients should not share EUCRISA with others, even if they exhibit similar symptoms, as it may cause harm.

Storage and Handling

The product is supplied in a tube that must be kept tightly closed to maintain its integrity. It should be stored at a temperature range of 20°C to 25°C (68°F to 77°F), with permissible excursions between 15°C and 30°C (59°F to 86°F). Proper storage conditions are essential to ensure the product's efficacy and safety.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Eucrisa as submitted by Pfizer Laboratories Div Pfizer Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)