Usage
- Crisaborole is prescribed for the topical treatment of mild to moderate atopic dermatitis (eczema) in adults and pediatric patients 3 months of age and older.
- Pharmacological classification: Phosphodiesterase-4 (PDE-4) inhibitor, nonsteroidal anti-inflammatory agent.
- Crisaborole’s mechanism of action is not fully understood, but it is thought to work by inhibiting PDE-4. This enzyme is overactive in atopic dermatitis, and its inhibition increases intracellular cyclic adenosine monophosphate (cAMP) levels, reducing inflammation. This action modifies downstream inflammatory pathways, including nuclear factor-κB and T-cell signaling.
Alternate Names
- INN: Crisaborole
- Brand name: Eucrisa
- Staquis (international variation)
How It Works
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Pharmacodynamics: Crisaborole reduces inflammation in atopic dermatitis by inhibiting PDE-4, thus increasing intracellular cAMP levels. This inhibits the inflammatory cascade associated with atopic dermatitis.
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Pharmacokinetics:
- Absorption: Crisaborole is absorbed systemically following topical application, reaching steady-state plasma concentrations by day 8 of twice-daily application. Approximately 25% of a topically applied dose is absorbed.
- Metabolism: Crisaborole is metabolized into two inactive metabolites. One metabolite shows some accumulation with repeated dosing. Crisaborole and its primary metabolite do not inhibit or induce major CYP450 enzymes. They also do not significantly interact with uridine 5’-diphospho-glucuronosyltransferases (UGTs), P-glycoprotein, organic anion or cation transporters, or breast cancer resistance protein. A secondary metabolite shows moderate inhibition of UGT1A9 and may moderately increase levels of sensitive UGT1A9 substrates.
- Elimination: The elimination pathways of crisaborole have not been fully characterized in humans.
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Mode of Action: Crisaborole inhibits PDE-4. This inhibition leads to increased intracellular cAMP, impacting downstream inflammatory signaling pathways relevant to atopic dermatitis.
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Receptor binding, enzyme inhibition, or neurotransmitter modulation: Crisaborole primarily acts through PDE-4 enzyme inhibition.
Dosage
Standard Dosage
Adults:
- Apply a thin layer of crisaborole ointment (2%) twice daily to affected areas. Once a clinical effect is achieved, the application frequency can be reduced to once daily.
Children:
- Children (3 months and older): Apply a thin layer of crisaborole ointment (2%) twice daily to affected areas. Once a clinical effect is achieved, the application frequency can be reduced to once daily.
- Children (younger than 3 months): Safety and efficacy have not been established.
Special Cases:
- Elderly Patients (≥65 years): No specific dosage adjustments are typically necessary. However, limited clinical trial data exists for this age group.
- Patients with Renal Impairment: No specific dosage adjustments are needed.
- Patients with Hepatic Dysfunction: No specific dosage adjustments are needed.
- Patients with Comorbid Conditions: Dosage adjustments may be necessary depending on the condition, but no specific guidance exists and adjustment is at the discretion of the physician.
Clinical Use Cases
Crisaborole is not indicated for use in intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is exclusively for topical treatment of mild to moderate atopic dermatitis.
Dosage Adjustments
No formal dose adjustments are recommended in renal or hepatic impairment.
Side Effects
Common Side Effects
- Application site pain (burning or stinging)
Rare but Serious Side Effects
- Hypersensitivity reactions (e.g., contact urticaria, pruritus, swelling, erythema)
Long-Term Effects
Long-term use of crisaborole has been studied for up to 52 weeks without revealing evidence of significant side effects, such as skin thinning, striae, or adrenal suppression.
Adverse Drug Reactions (ADR)
Hypersensitivity reactions, including angioedema and anaphylaxis, have been reported during post-marketing surveillance.
Contraindications
- Hypersensitivity to crisaborole or any of the components of the ointment.
Drug Interactions
- No clinically significant drug interactions have been identified.
Pregnancy and Breastfeeding
- Pregnancy: Limited data are available on crisaborole use in pregnant women. Animal studies have not shown adverse developmental effects. However, maternal toxicity and adverse fetal effects were observed at high doses in animal studies.
- Breastfeeding: It is unknown if crisaborole is present in human milk. Crisaborole is absorbed systemically. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for crisaborole and any potential adverse effects on the breastfed child from crisaborole or from the underlying maternal condition.
Drug Profile Summary
- Mechanism of Action: PDE-4 inhibitor, increases intracellular cAMP, reduces inflammation.
- Side Effects: Application site pain, hypersensitivity reactions.
- Contraindications: Hypersensitivity to crisaborole.
- Drug Interactions: No clinically significant interactions identified.
- Pregnancy & Breastfeeding: Limited human data; use with caution.
- Dosage: Apply a thin layer twice daily to affected skin; reduce to once daily maintenance as appropriate.
- Monitoring Parameters: Monitor for treatment efficacy (improvement in atopic dermatitis signs and symptoms) and potential hypersensitivity reactions.
Popular Combinations
Crisaborole is typically used as monotherapy. Emollients may be used on unaffected areas. It is not recommended to apply crisaborole concomitantly with other topical products to treat atopic dermatitis on the same skin area.
Precautions
- General Precautions: Use cautiously in patients with a history of hypersensitivity reactions. Avoid contact with eyes, mouth, and vagina.
- Pregnant Women: Limited human data. Assess risk/benefit.
- Breastfeeding Mothers: Unknown if present in human milk; assess risk/benefit.
- Children & Elderly: Safe and effective in children 3 months and older. Limited data in patients older than 65.
- Lifestyle Considerations: No specific lifestyle considerations have been identified.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Crisaborole?
A: Apply a thin layer of crisaborole ointment (2%) twice daily to the affected skin. For maintenance therapy, once-daily application may be sufficient.
Q2: What are the common side effects of Crisaborole?
A: The most common side effect is application site pain, such as burning or stinging.
Q3: How does Crisaborole work?
A: Crisaborole inhibits PDE-4, which leads to an increase in intracellular cAMP, reducing inflammation associated with atopic dermatitis.
Q4: Can Crisaborole be used in children?
A: Yes, Crisaborole is approved for use in children 3 months of age and older.
Q5: Can Crisaborole be used during pregnancy or breastfeeding?
A: Data in pregnant and breastfeeding women are limited. Use with caution after assessing the risk-benefit ratio with the patient.
Q6: Are there any drug interactions with Crisaborole?
A: No clinically significant drug interactions have been identified.
Q7: How long can Crisaborole be used?
A: Crisaborole is safe for long-term use. Clinical trials have evaluated its use for up to 52 weeks.
Q8: What should I do if a patient experiences a hypersensitivity reaction to Crisaborole?
A: Discontinue Crisaborole immediately and initiate appropriate therapy (e.g., antihistamines, corticosteroids).
Q9: Can Crisaborole be used on the face?
A: Yes, Crisaborole can be used on all skin areas affected by atopic dermatitis, including the face, head, and neck.
Q10: Can Crisaborole be used with other topical eczema medications?
A: Concomitant use of crisaborole with other topical eczema medications on the same skin area is not recommended. Emollients may be used on unaffected areas.
