Crisaborole

Uses

Crisaderm contains 2% Crisaborole (w/w) in a petrolatum-based, white to off-white ointment and is for topical use. The active ingredient, Crisaborole, is a phosphodiesterase-4 (PDE-4) inhibitor, mainly acting on phosphodiesterase 4B (PDE4B), which causes inflammation. Chemically, Crisaborole is a phenoxybenzoxaborole. It contains a boron atom that helps penetrate the skin and is essential for its binding activity. Inhibition of PDE4B appears to suppress the release of tumor necrosis factor alpha (TNFα), interleukin-12 (IL-12), IL-23 and other cytokines, proteins believed to be involved in the immune response and inflammation.

Crisaborole is also used to associated treatment for these conditions: Mild Atopic dermatitis, Moderate Atopic dermatitis

How Crisaborole works

Inhibition of PDE4 by crisaborole leads to elevated levels of cyclic adenosine monophosphate (cAMP). Increased intracellular levels of cAMP inhibit the NF-kB pathway and suppress the release of pro-inflammatory mediators such as TNF-alfa and various interleukins that play a causative role in psoriasis and atopic dermatitis. Suppression of downstream effects in different cell types may explain the therapeutic role of crisaborole in immune-mediated skin diseases.

Dosage

Crisaborole dosage

Apply a thin layer of Crisaderm twice daily to affected areas. Crisaderm is for topical use only and not for ophthalmic, oral, or intravaginal use.

Side Effects

Allergic reactions- Crisaderm may cause allergic reactions at or near the application site. These can be serious and may include hives, itching, swelling, and redness. The most common side effect of Crisaderm is application site pain, such as burning or stinging.

Toxicity

Hypersensitivity reactions such as contact urticaria may occur and discontinuation of the treatment is advised. No evidence of mutagenic or clastrogenic potential as well as altered effects on fertility. Oral LD50 value for rats is >500mg/kg.

Precaution

Hypersensitivity reactions, including contact urticaria have occurred in patients treated with Crisaderm. If signs and symptoms of hypersensitivity occur, discontinue Crisaderm immediately and initiate appropriate therapy.

Food Interaction

Elimination Route

Systemic concentrations of crisaborole were reached by 8 days of twice-daily topical administration. It has low systemic absorption thus poses less risk for developing systemic side effects.

Elimination Route

Renal excretion of metabolites is the major route of elimination.

Pregnancy & Breastfeeding use

Risk Summary:

PregnancyThere is no available data with Crisaderm in pregnant women to inform the drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, there were no adverse developmental effects observed with oral administration of crisaborole in pregnant rats and rabbits during organogenesis at doses up to 3 and 2 times, respectively, the maximum recommended human dose (MRHD).

Risk Summary:

LactationThere is no information available on the presence of Crisaderm in human milk. Crisaderm is systemically absorbed. The lack of clinical data during lactation precludes a clear determination of the risk of Crisaderm to a breastfed infant.

Interaction with other Medicine

In vitro studies using human liver microsomes indicated that under the conditions of clinical use, Crisaborole and metabolite 1 are not expected to inhibit cytochrome P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4.

In vitro human liver microsomes studies for metabolite 2 showed that it did not inhibit activities of CYP2C19, 2D6, and 3A4.

Storage Condition

Do not store above 30 degree Celsius. Keep away from light and out of the reach of children.

Innovators Monograph

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