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-