Transitioning From Brand to Generic With Topical Products and the Importance of Maintaining the Formulation and Therapeutic Profiles of the Original Product: Focus on Clocortolone Pivalate 0.1% Cream

dition, unlike other structural classes of TCS, the clocortolone pivalate molecule is associated with a very low rate of inherent allergenicity, a factor that is clinically relevant as TCS allergy is easily misdiagnosed. ^8,9,13

As mid-potency TCS are commonly used to treat eczematous dermatoses that are associated with marked increase in transepidermal water loss (TEWL) and decreased stratum corneum (SC) hydration, the emollient cream vehicle was designed to include very few excipients. Some excipients were selected specifically to help improve the SC permeability barrier that is impaired in many eczematous and inflammatory dermatoses. ^11,12-18 The inclusion of “barrier friendly excipients,” such as white petrolatum, mineral oil, and stearyl alcohol, provides adjunctive clinical benefit and may reduce the potential for irritant contact reactions and secondary xerotic skin changes.^13-18 The further rationale of incorporating vehicle components that can assist in reducing SC permeability barrier impairment is to counteract potential adverse sequelae that TCS application can have on the SC, which result primarily from a decrease in SC lipid synthesis at sites of application.¹⁹

The excipients included in both the original brand and authorized generic clocortolone pivalate 0.1% cream and their primary vehicle functions that are likely to be clinically relevant are listed in Table 1. The 3 major excipients included in the clocortolone pivalate 0.1% cream that have emollient properties and can enhance the functional integrity of the SC permeability barrier are white petrolatum (occlusive emollient), mineral oil (light non-vegetable oil occlusive emollient), and stearyl alcohol (long-chain fatty alcohol emollient).¹⁰ All 3 of these agents are well established as vehicle excipients that have been used for decades in many skin-care products with a very favorable track record of skin tolerability and safety. Mineral oil has been applied to skin for cosmetic purposes since the late 1800s.²⁰ Stearyl alcohol is a commonly used fatty alcohol, which provides lubricant and emollient characteristics to skin and serves as both a non-toxic emulsifier and a slight thickening agent that assists in providing a “creamy” quality to the formulation.²¹ Ultimately, these 3 excipients function collectively to assist clocortolone pivalate by promoting skin hydration at the sites of active skin disease whilst the clocortolone pivalate is functioning to reduce cutaneous inflammation caused by the skin disease itself. As a TCS is not to be conceptualized as a “moisturizer,” patients are still encouraged to use a gentle cleanser and moisturizer or “barrier repair” formulation diffusely, especially those patients with AD, asteatotic eczema, and xerotic skin, where replenishment of SC lipids and increased hydration provide adjunctive benefit.^{4,15-17,20-23} However, inclusion in a TCS formulation of excipients that enhance the SC permeability barrier helps to sustain its proper function in areas of eczematous dermatitis where the TCS is being applied. ¹⁹

Another important characteristic of a TCS formulation is the avoidance of ingredients that can be allergenic or induce irritancy. Clocortolone pivalate 0.1% cream does not contain any fragrances or lanolin, both of which can be problematic in eczematous dermatitis, such as AD.^10,13,23 An additional advantage of clocortolone pivalate 0.1% cream is the absence of penetration enhancers, such as propylene glycol (in high concentrations) or ethanol, which can induce allergenicity, irritancy, and/or SC barrier impairment.^11,13,15 A final comment about cutaneous allergenicity is worthy of mention. The clocortolone pivalate molecule falls into TCS Category C within the classification system used to differentiate the potential for different TCSs to induce ACD.⁸ This category exhibits the lowest potential risk for ACD induced by a topically applied corticosteroid compound (<0.2%).^24,25

Importantly, all of the favorable characteristics demonstrated by the original brand of clocortolone pivalate 0.1% cream apply also to the authorized generic clocortolone pivalate 0.1% cream because the formulations are identical and produced by the same manufacturer.

A total of 18 healthy adult female subjects were enrolled in the treatment phase of a study that evaluated the effects of clocortolone pivalate 0.1% cream, hydrocortisone butyrate 0.1% lipocream (HB-LC), and hydrocortisone butyrate 0.1% lotion (HB-L) on both TEWL and skin hydration.²⁶ Each subject was instructed to stop the use of all topical products with effects on skin moisturization (ie, soaps, creams, lotions, sunscreens, insect repellants, etc.) on their upper extremities during a 3-day pre-conditioning period prior to testing. On day 1, four 5cm x 5cm sites (2 sites on each volar forearm) were identified and underwent “dry shaving” as a method to induce SC permeability barrier dysfunction. Both increased TEWL and decreased skin hydration have been shown to occur using this methodology. On day 2, baseline measurements for TEWL and corneometry were obtained using recognized instrumentation from each of the 4 dry-shaved volar forearm sites and 1 nonshaved, non-treated off-site located to the side of one volar forearm prior to treatment. Measurements were repeated 1 hour (± 10 minutes), 2 hours (± 15 minutes), and 4 hours (± 15 minutes) after each subject underwent application to a given test site of a defined amount of clocortolone pivalate 0.1% cream, HB-L, and HB-LC, with the fourth dry shaved skin site left untreated to serve as “damaged control skin.” As noted above, a site of normal undamaged skin was also identified to serve as a “normal skin control.” Before each set of measurements was taken, subjects were required to acclimate in the environmentally-controlled room for 30 to 45 minutes. The results of this study are depicted in Figure 1 and Figure 2, demonstrating, based on this assay, that clocortolone piva-