Crisaderm

Approved Indications:

• Mild to Moderate Atopic Dermatitis (Eczema):
  – For the topical treatment of mild to moderate atopic dermatitis in adults and pediatric patients aged 3 months and older.

Clinically Accepted Off-label Uses:

• Seborrheic Dermatitis (Mild-to-moderate cases):
  – Used off-label in some patients to manage inflammation and irritation.
• Contact Dermatitis:
  – May help reduce inflammation in allergic or irritant contact dermatitis.
• Intertrigo and sensitive skin inflammation:
  – Occasionally used as a non-steroidal anti-inflammatory alternative for sensitive areas (e.g., face, groin, underarms).

• Adults and Pediatric Patients (≥3 months):
  – Apply a thin layer of Crisaborole 2% ointment to the affected areas twice daily (morning and evening).
  – Gently rub into the skin until absorbed.
• Route:
  – Topical application only; not for oral, ophthalmic, or intravaginal use.
• Duration:
  – Continue until lesions are resolved. Evaluate therapy after 28 days. Long-term use should be guided by clinical response.
• Elderly:
  – Same dosing as adults; no specific age-related dosage adjustment is required.
• Renal/Hepatic Impairment:
  – No dose adjustments needed; systemic absorption is minimal.

Crisaborole is a non-steroidal topical phosphodiesterase-4 (PDE4) inhibitor. It works by inhibiting the enzyme PDE4 in skin cells, which leads to an increase in intracellular cyclic adenosine monophosphate (cAMP). Elevated cAMP levels reduce the production of pro-inflammatory cytokines such as TNF-α, IL-2, IL-4, and IL-31. This anti-inflammatory effect alleviates symptoms such as redness, itching, and swelling associated with atopic dermatitis without the use of corticosteroids.

• Absorption:
  – After topical application, systemic absorption is low.
  – Approximately 25% of the applied dose may be absorbed systemically.
• Distribution:
  – Systemically absorbed crisaborole distributes minimally beyond local tissue.
• Metabolism:
  – Primarily metabolized via esterase-mediated hydrolysis to inactive metabolites.
• Elimination:
  – Metabolites are excreted primarily through the urine.
• Half-life:
  – Estimated systemic half-life is ~1 hour (based on metabolite profiles).
• Onset of Action:
  – Symptomatic improvement may be seen in as early as 7 days, though full response may require up to 28 days.

• Pregnancy:
  – Not assigned a formal FDA pregnancy category.
  – Animal studies have shown no fetal harm.
  – Use during pregnancy only if the potential benefit outweighs the risk.
• Lactation:
  – It is unknown if crisaborole is excreted in breast milk.
  – Low systemic absorption suggests low risk; avoid application to nipple area or areas in direct infant contact.
• Caution Advised:
  – Limited human data; use only when clearly indicated.

• Primary Class: Topical Anti-inflammatory Agent
• Subclass: Non-steroidal Phosphodiesterase-4 (PDE4) Inhibitor
• Generation: First-in-class topical PDE4 inhibitor for atopic dermatitis

• Known hypersensitivity to crisaborole or any component of the formulation
• Application on infected skin lesions, including active bacterial, viral, or fungal infections without concurrent antimicrobial treatment
• Severe forms of dermatitis requiring systemic therapy

• Hypersensitivity Reactions:
  – Cases of contact urticaria, angioedema, and anaphylaxis have been reported; discontinue use if symptoms appear.
• Use on Broken or Severely Inflamed Skin:
  – Not recommended for use on open wounds, severely excoriated skin, or infected areas.
• Ocular Exposure:
  – Avoid contact with eyes; rinse thoroughly with water if contact occurs.
• Monitoring:
  – Assess for worsening eczema or signs of infection during therapy.
• Pediatric Use:
  – Safe in infants ≥3 months; safety not established under this age.

• Common (≥1%):
  – Application site burning or stinging
  – Application site pain or irritation
• Less Common:
  – Contact dermatitis
  – Urticaria
• Rare/Serious:
  – Hypersensitivity reactions (angioedema, anaphylaxis)
• Timing:
  – Local reactions usually occur within the first 2–5 days of use and are generally mild and transient.

• Drug–drug interactions:
  – No significant systemic interactions due to minimal systemic absorption.
• Topical combination:
  – Avoid concurrent use with strong topical irritants (e.g., salicylic acid, benzoyl peroxide) without medical supervision.
• Enzyme interactions:
  – No known CYP450-mediated metabolism; not an inducer or inhibitor of major isoenzymes.
• Food and Alcohol:
  – No known interactions.

• FDA approval extended to include pediatric use in infants as young as 3 months (previously ≥2 years).
• 2022–2024 Atopic Dermatitis Guidelines (AAD, EADV):
  – Recommend crisaborole as a first-line non-steroidal option in mild-to-moderate eczema, especially for sensitive areas like the face and intertriginous zones.
• New data supports its long-term safety profile over corticosteroids for chronic use.

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C.
• Keep tube tightly closed when not in use.
• Protect from excessive heat or freezing.
• Do not refrigerate.
• Keep out of reach of children.
• Discard after expiration date indicated on the package.