crisaborole topical (Rx)

1-10%

Application site pain, burning, or stinging (4%)

<1%

Contact urticaria

Postmarketing Reports

Allergic contact dermatitis

Contraindications

History of hypersensitivity to crisaborole or any component of the formulation

Cautions

Hypersensitivity reactions reported, including contact urticaria; signs and symptoms may include severe pruritus, swelling, and erythema at the application site or at a distant site; discontinue immediately and initiate appropriate therapy if hypersensitivity suspected (see Contraindications)

Pregnancy

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

Crisaborole is systemically absorbed

Animal studies

• No adverse developmental effects observed in animal reproduction studies, with oral administration of this drug in pregnant rats and rabbits during organogenesis at doses up to 3 and 2 times, respectively, the maximum recommended human dose (MRHD)

Lactation

Unknown if distributed in human breast milk

Crisaborole is systemically absorbed

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Phosphodiesterase (PDE)-4 inhibitor; results in increased intracellular cyclic adenosine monophosphate (cAMP) levels

The specific mechanism by which crisaborole exerts its therapeutic action for atopic dermatitis is not well defined, although cAMP is thought to decrease the proinflammatory response (eg, cytokine release) associated with atopic dermatitis

Absorption

Steady-state reached on Day 8

Peak plasma concentration: 188 ng/mL

AUC: 1164 ng⋅hr/mL

Distribution

Protein bound: 97%

Metabolism

Substantially metabolized into inactive metabolites

Major metabolites: 5-(4-cyanophenoxy)-2-hydroxyl benzyl alcohol (metabolite 1) is formed via hydrolysis; it is further metabolized into downstream metabolites, among which 5-(4-cyanophenoxy)-2-hydroxyl benzoic acid (metabolite 2), formed via oxidation, is also a major metabolite

Elimination

Excretion: Renal excretion of metabolites is the major route of elimination

Topical Administration

Apply thin layer of ointment to affected areas BID

Wash hands after applying ointment, unless hands are being treated

For topical use only; not for ophthalmic, oral, or intravaginal use

Storage

Store at controlled room temperature 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)