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

July 2014 | Volume 13 | Issue 7 | Supplement Individual Articles | 77 | Copyright © July 2014

James Q. Del Rosso DO FAOCDa and Leon H. Kircik MDb

aLas Vegas Skin and Cancer Clinics/West Dermatology Group, JDRx Dermatology LL C, Henderson, NV;
Touro University College of Osteopathic Medicine, Henderson, NV
bIndiana University School of Medicine, Indianapolis, IN; Icahn School of Medicine at Mount Sinai, New York, NY;
Physicians Skin Care, PLL C, Louisville, KY

since 1977. This formulation is supported by data demonstrating efficacy in patients treated for a variety of common corticosteroidresponsive dermatoses (CRD), an excellent safety profile, a vehicle design which includes excipients that assist in reducing epidermal barrier dysfunction, and an active ingredient that exhibits negligible potential for allergenicity.9-12 Therefore, when considering the availability of a generic formulation of clocortolone pivalate 0.1% cream, it is important that the quality and characteristics of the original brand formulation be upheld. Unfortunately, this is not always the case with generic formulations as the vehicle constituents and characteristics sometimes differ from the original brand formulation. As a result, clinicians may assume that their patients are being treated with a TCS product that delivers the qualities they have become accustomed to, when in fact a generic formulation may be very different in its formulation design other than for the active ingredient and its concentration.

The Brand vs Generic Debate

When confronted with a clinical scenario in which a mid-potency TCS is desired, the clinician has several compounds and formulations to choose from and will often make the selection based on their familiarity with the efficacy and tolerability of a given compound and product, and the type of vehicle that is adaptable for application to the anatomic areas affected. Importantly, in many cases this familiarity is based on their prior use of a given brand name product that is a consistent formulation in terms of its components and physiochemical characteristics. Many generic mid-potency TCS formulations differ from the brand in the excipients they contain, which in some cases may alter the physiochemical, efficacy, and tolerability characteristics of the final product.9-12
The approval of a generic topical formulation is based on assumptions of efficacy and tolerability from pivotal trials completed with the original branded formulation. Therefore, assessment of the clinical performance, skin tolerability, and safety of a generic formulation is left up to clinicians based on outcomes they observe in their patients, assuming they are fully aware of which product the patient actually used. Occasionally, the altered characteristics of the generic formulation may be clinically relevant, with the generic formulation exhibiting a relative lack of efficacy, greater potential for skin irritancy, possible contact allergy due to a specific excipient not used in the brand formulation, or inferior aesthetic characteristics. However, there appear to be no clinically relevant differences in many cases between the use of generic formulations as compared to their respective original brand products. Due to the vast array of generic TCS formulations that are available for pharmacies to stock and dispense, the clinician is confronted with a self-imposed question regarding the physiochemical properties, pharmacokinetic profile, efficacy, tolerability, and safety of different generic TCS formulations that may be dispensed to a given patient.9
How can questions about potential differences between brand and generic products be resolved with some certainty? With clocortolone pivalate 0.1% cream, its manufacturer is providing an authorized generic formulation that is identical to the brand formulation of clocortolone pivalate 0.1% cream (Cloderm® Cream; Promius Pharma, LLC; Princeton, NJ), a mid-potency TCS emollient cream approved in the United States by the Food and Drug Administration in 1977 for the treatment of CRDs.5,10 This article discusses characteristics of the clocortolone pivalate compound, the clocortolone pivalate 0.1% cream formulation, and the data on efficacy and safety, with an emphasis on clinical relevance and practical application. The comfort level for the clinician is that this specific generic formulation will provide the same TCS product as the brand formulation, thus delivering the results to which they are accustomed if they have prescribed clocortolone pivalate 0.1% cream in the past, and results supported by evidence from clinical trials and safety data with the original brand product.10-13
The following is a comprehensive profile of the data available with the original brand formulation of clocortolone pivalate 0.1% cream, which can then be applied with certainty to the authorized generic formulation that is the identical product.

Pharmacologic Profile

A major part of developing a TCS product is the selection of the active ingredient. With clocortolone pivalate, the molecular chemists structurally modified the basic corticosteroid structural nucleus through the step-wise addition of specific molecules or side chains at different molecular positions to enhance lipophilicity and cutaneous penetration, increase potency, and counter potential structural interferences with glucocorticosteroid-receptor (GR) binding and other modifications that enhance GR-binding affinity.2,3,5,6,11 One example of a structural modification made to produce clocortolone pivalate is esterification at the C21 position with substitution of a pivalate group that increases lipophilicity and inherent potency and decreases metabolic breakdown, resulting in prolonged tissue exposure. Another is methylation at the C16 position, which also increases lipophilicity and decreases allergenicity.5,11 The collective modifications resulted in clocortolone pivalate, which was then incorporated into an emollient cream vehicle. In ad-