Clocortolone Pivalate: A Topical Corticosteroid With a Unique Structure
February 2013 | Volume 12 | Issue 2 | Supplement | s3 | Copyright © 2013
Leon H. Kircik MD
No abstract available
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Clinicians treating corticosteroid-responsive dermatoses, such as atopic dermatitis, contact dermatitis, other eczematous dermatoses, seborrheic dermatitis, and psoriasis have a number of treatment options. The selection of a topical corticosteroid (TCS) depends on several different factors, such as potency, formulation, dosage, cosmetic elegance, and cost considerations, including third-party coverage. Among these, clocortolone pivalate cream 0.1% (Cloderm® Cream; Promius Pharma, L.L.C., Bridgewater, NJ), which was introduced into the market more than 3 decades ago, has withstood the test of time and remains a versatile treatment option. It is an effective, midpotency (Class 4) TCS formulation with a favorable safety profile, including a low rate of contact sensitization (Category C). The formulation also has no generic equivalent, which makes legal substitution impossible.
As explored in the following pages, evidence shows that the unique molecular structure of clocortolone pivalate contributes to the skin penetration and the potency of the drug. All TCS molecular structures are based on hydrocortisone, and therefore, structural modifications influence efficacy, safety, and tolerability, as well as allergenicity. In the case of clocortolone pivalate, for example, halogenation at C-6 and C-9 appears to permit the drug to function like a midpotent corticosteroid while still maintaining a favorable safety profile.
The general perception in the dermatology community has been that halogenation is associated with an increased risk for adverse events, especially those involving skin, such as atrophy and striae. However, we now know that it is the location of the halogen atom and the type of the halogen atom that mediates safety rather than the halogenation itself; and therefore the simple presence of the halogen atoms does not increase the severe adverse events in clocortolone pivalate.1 Moreover, with methylation at the C-16 position and esterification at the C-17 position, clocortolone pivalate belongs to Category C corticosteroids, with minimal risk of allergenicity.2 Since contact sensitization to TCS may be very difficult to diagnose and confirm, and therefore is likely to be underdiagnosed, TCS-induced allergic contact dermatitis is a challenging problem for clinicians. Lastly, substitution of the pivalate group at C-21 increases lipid solubility of clocortolone pivalate. Clocortolone pivalate offers high lipid solubility, which seems to facilitate more rapid percutaneous absorption into skin, allowing access to the therapeutic target site without any apparent risk of increased adverse events based on results from several clinical trials.3
Phase 3 clinical trial data have demonstrated the efficacy and tolerability of clocortolone pivalate 0.1% cream in several steroid-responsive dermatoses. In studies for atopic dermatitis and other eczematous dermatoses, statistically significant improvement relative to placebo was seen at day 4.4 In psoriasis trials, clocortolone pivalate 0.1% cream demonstrated superiority to vehicle by day 7, continuing at days 14, 21, and 28. This early onset of action will contribute to increased compliance in our patients. Also, in a study to assess the effects of clocortolone pivalate 0.1% cream on hypothalamic–pituitary–adrenal axis function, there was no evidence of adrenal suppression over the 21-day trial period, as measured by urinary 17-ketosteroids.5 The use of clocortolone pivalate 0.1% cream in sensitive locations such as the face and intertriginous areas in clinical trials is another tribute to the excellent safety profile of this TCS.6
Finally, the emollient cream vehicle base may be dispensed in either a tube or a pump, offering both flexibility to prescribers and convenience to patients. The pump may be especially useful for ensuring that the patient uses an appropriate amount of medication. The vehicle base of clocortolone pivalate 0.1% cream is composed primarily of water and emollient ingredients (white petrolatum, mineral oil, and stearyl alcohol) and few preservatives.7 In my practice, patients consistently report a high rate of satisfaction and cosmetic elegance with this product.