Crisaborole is a topical anti-inflammatory drug used primarily for the treatment of mildto moderate atopic dermatitis (eczema). Its development represents a shift toward non-steroidal topical therapies, aiming to reduce inflammation with fewer long-term side effects compared to corticosteroids.
Crisaborole was developed and approved in the 2010s as a targeted therapy that inhibits phosphodiesterase-4 (PDE-4), an enzyme involved in the inflammatory pathway. By blocking PDE-4, it increases intracellular cyclic AMP (cAMP) levels, which in turn reduces the production of pro-inflammatory cytokines, thereby decreasing skin inflammation and symptoms such as redness, itching, and swelling.
BRAND NAMES
Eucrisa (most widely used internationally, including the U.S.)
MECHANISM OF ACTION
Crisaborole acts by selectively inhibiting Phosphodiesterase-4 (PDE-4), an enzyme responsible for breaking down cyclic adenosine monophosphate (cAMP) within inflammatory cells. Inhibition of PDE-4 leads to increased intracellular cAMP levels, which in turn suppress the release of pro-inflammatory cytokines such as TNF-α and interleukins. This results in reduced inflammation, erythema, and pruritus associated with conditions like atopic dermatitis, thereby improving skin symptoms.
PHARMACOKINETICS
Absorption
Crisaborole is administered topically as an ointment and is absorbed through the skin into systemic circulation. The extent of absorption depends on factors such as the condition of the skin (higher in inflamed or damaged skin), surface area of application, and duration of use.
Distribution
The volume of distribution of Crisaborole is not well-defined or not formally established, as it is primarily used as a topical agent with limited systemic exposure.
Metabolism
Crisaborole is rapidly metabolized after absorption, primarily in the liver. It undergoes hydrolysis to form inactive metabolites, mainly boron-containing metabolites (such as AN7602), followed by further oxidation.
Elimination
Crisaborole is eliminated primarily in the form of its inactive metabolites, which are excreted mainly via the kidneys in urine. A smaller portion may be eliminated through feces.
PHARMACODYNAMICS
Crisaborole is a selective inhibitor of Phosphodiesterase-4 (PDE-4) in inflammatory and immune cells of the skin. By inhibiting PDE-4, it prevents the breakdown of cyclic adenosine monophosphate (cAMP), leading to increased intracellular cAMP levels. Elevated cAMP suppresses activation of immune cells and reduces the release of pro-inflammatory cytokines such as TNF-α, IL-2, and IL-4. This results in decreased cutaneous inflammation, erythema, and pruritus, thereby improving the clinical manifestations of atopic dermatitis.
ADMINISTRATION
Crisaborole is administered topically as a 2% ointment. It is applied as a thin layer to the affected areas of skin twice daily (BID). The drug is intended for external use only and should be applied to clean, dry skin. It can be used on most body areas, including sensitive regions, but care should be taken to avoid contact with the eyes, mouth, and mucous membranes. In conditions such as atopic dermatitis, treatment is continued until symptoms improve or as directed by a healthcare provider.
DOSAGE AND STRENGTH
It is used in patients with mild to moderate atopic dermatitis, and the amount applied depends on the size and extent of the affected skin. Treatment should be continued until symptoms resolve or as advised by a healthcare professional.
DRUG INTERACTIONS
Crisaborole has minimal clinically significant drug interactions due to its low systemic absorption after topical application. It is not known to interact significantly with systemic medications because it is rapidly metabolized mainly by hydrolysis rather than cytochrome P450 enzymes.
FOOD INTERACTIONS
Crisaborole has no known clinically significant food interactions because it is administered topically and has minimal systemic absorption. Food intake does not affect its absorption, distribution, metabolism, or elimination.
CONTRAINDICATIONS
Crisaborole is contraindicated in patients with known hypersensitivity to crisaborole or any component of the formulation. It should not be used in individuals who have previously experienced allergic reactions such as contact dermatitis, urticaria, or severe skin irritation related to the drug.
SIDE EFFECTS
Application site pain (burning or stinging sensation)
Application site pruritus (itching)
Application site erythema (redness)
Application site dermatitis or irritation
Hypersensitivity reactions (rare)
Contact dermatitis
Skin rash
OVER DOSE
Overdose with Crisaborole is unlikely due to its topical route of administration and low systemic absorption. Excessive or prolonged application may, however, increase the risk of local skin reactions such as burning, stinging, erythema, or irritation.
TOXICITY
Crisaborole has a low toxicity profile due to its limited systemic absorption when applied topically. In therapeutic use for atopic dermatitis, significant systemic toxicity is rare. Most observed adverse effects are localized to the skin, including burning, stinging, erythema, and irritation at the site of application.
