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Supported by Promius Pharma, LLC.
Clinical Insights
2011, No. 3
Clocortolone pivalate cream 0.1%:
A Versatile Treatment Option for a
Range of Common Dermatoses
Joseph Bikowski, MD, FAAD
Clinical Assistant Professor of Dermatology,
Ohio State University, Columbus, OH;
Director, Bikowski Skin Care Center, Sewickley, PA
T
opical corticosteroids are used in the management of a
wide range of dermatologic conditions. Since they were
introduced more than a half-century ago, they have
grown to comprise the most widely prescribed topical drug
class and continue to grow.1 Primarily anti-inflammatory, they
are thought to provide their effects via actions on mediator
release and function, inflammatory cell function, and release of
lysosomal enzymes.2
Among topical corticosteroids currently on the market, clocortolone pivalate cream 0.1% (Cloderm® Cream, Promius
Pharma, LLC) is an effective, upper mid-potency (class 4) steroid
formulation with a wide range of potential clinical uses. The
molecule, developed in the 1970s and introduced on the market in 1977, was specially designed to provide certain features
that can optimize the patient experience.
The unique molecular structure of clocortolone pivalate
enhances the potency and penetration of the drug, while also
presenting a favorable safety profile. From a practical standpoint, the cosmetically elegant, moisturizing cream encourages
patient satisfaction, and the versatile dosing options—a tube
and pump—offer convenience.
Cloderm Cream’s broad indication includes the relief of the
inflammatory and pruritic manifestations of corticosteroidresponsive dermatoses. Successful phase III clinical trials to
support FDA approval of Cloderm Cream were undertaken in
eczema and atopic dermatitis, psoriasis, contact dermatitis,
and seborrheic dermatitis.
Clocortolone Pivalate Structure
Despite their widespread and efficacious use in dermatology,
corticosteroids have historically been associated with certain
adverse effects.3 The most frequent adverse effects associated
with topical corticosteroids include atrophy, striae, acneiform
eruption, and purpura, while hypertrichosis, pigmentation
alterations, delayed wound healing, and exacerbation of skin
infections occur less frequently.3 Another risk associated with
topical corticosteroid use is steroid use/abuse/misuse dermatitis, previously often termed steroid rosacea or perioral dermatitis.4,5 The rate of contact sensitization for corticosteroids has
also garnered attention recently. Though the rate of sensitization is considerably higher than generally believed,3 sensitization is nonetheless uncommon.
The incidence of adverse effects is known to increase relative to the potency of the corticosteroid molecule and with
prolonged use. There are corticosteroid formulations available on the market in seven potency categories from 1
(Superpotent) to 7 (Lowest potency). While clinicians invariably prescribe across these categories, depending on the
severity of the condition being treated, a majority of patients
will be treated with a corticosteroid in the mid-potency
range. A class 4 upper mid-potency steroid, Cloderm Cream
has no generic equivalent.
The topical corticosteroids now on the market have been
chemically engineered from hydrocortisone, the prototype corticosteroid.2,6,7 All adrenal steroids share the same basic structure: three 6-carbon rings (A,B,C) and a single 5-carbon ring (D).
(Fig. 1) All corticosteroids are 21-carbon compounds with a 2carbon side chain at C17. Chemical modifications of the basic
corticosteroid structure yield changes in steroid potency.7
Clocortolone pivalate, the active ingredient in Cloderm
Cream, incorporates many of the structural modifications
associated with increased anti-inflammatory activity and percutaneous absorption. These include β-hydroxylation at C11, methylation at C-16, double-bonds at C-1,2, esterification
at C-21, and halogenation at C-6 and C-9 (Fig. 1). Because
some older halogenated products were associated with significant adverse effects, many clinicians became wary of halogenated corticosteroids.7 However, evidence shows that the
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, irritation, dryness, and folliculitis. Cloderm
Cream is contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
Supported by Promius Pharma, LLC.
Fig. 1. Molecular structure of clocortolone pivalate
Chemical modifications associated with
improved anti-inflammatory activity
and improved percutaneous
absorption are shown in
bold and blue.
topical corticosteroids that are lipid soluble possess greater
anti-inflammatory potency than more polar molecules,
owing to their higher concentrations in the viable epidermis.8 In studies of steroid percutaneous absorption, the
most lipid soluble corticosteroids penetrated the stratum
corneum at the fastest rates and were better delivered, with
the highest epidermal concentrations.8
Furthermore, esterification at C-21 with substitution of the
pivalate group increases duration of action, influences potency, and increases lipid solubility (Fig. 2). While substitution of a
group as large as pivalate is likely to reduce glucocorticoid
receptor affinity,9 the additional methyl group increases lipid
solubility. Clocortolone pivalate has higher lipid solubility than
other commonly used mid-strength topical corticosteroids
(Fig. 2).10
Patient Experience
More rapid penetration and accumulation of active drug in
the epidermis is expected to contribute to a rapid onset of
position and nature of the halogen atoms (in this case chlo- therapeutic effect, and this has been seen with Cloderm
rine and fluorine), not simply their presence, determine both Cream. In fact, in phase III clinical trials, treatment with
the potency and the incidence of adverse events.7 No other Cloderm Cream provided a rapid onset of therapeutic effect
topical corticosteroid has Cloderm Cream’s unique C9 chlo- among patients with eczema and atopic dermatitis.11
rination and C6 fluorination, associated with mid-strength Statistically significant improvement relative to placebo was
potency.
seen at Day 4. The frequency of adverse reactions was low.
In addition to its potency, the unique chemical structure Despite its rapid penetration, no HPA-axis suppression (as
of clocortolone pivalate contributes to its high lipophilicity, determined by plasma cortisol levels) was observed in a 10which aids rapid epidermal penetration. Formulating corti- subject study where Cloderm Cream was applied under
costeroids for topical delivery presents the challenge of occlusion for 21 days.7,12
penetrating the skin barrier. Lipid solubility is a major deterIn the phase III atopic dermatitis study, treatment with
minant of both drug absorption and drug penetration Cloderm Cream provided statistically significantly greater
through the stratum corneum.2 It is generally accepted that effect than placebo, beginning at Day 4. The bi-lateral, splitbody study measured objective criteria,
such as erythema, edema, transudation,
Fig. 2. Lipophilicity
and, if present, bullae and vesicles,
papules, plaques, scaling, crusting, fissures,
and lichenification. Subjective measures
included relief of pain, itching, or burning.
Cloderm Cream statistically significantly
out-performed its vehicle base in both
objective and subjective measures at all
time points. It is interesting to note, however, that there was an appreciable level of
patient satisfaction with the vehicle base at
all time points, and a fair number of subjects achieved “satisfactory” therapeutic
response to placebo early on. There were
no adverse reactions observed throughout
the trial period.12
In psoriasis trials, Cloderm cream demonstrated superiority to placebo by Day 7 (continuing at Days 14, 21, and 28). The rate of
Partition ratios of commonly used mid-strength topical corticosteroids (TCS). The
reported adverse events was low and actualpartition ratio represents the concentration of drug in each phase of an immiscible
mixture of octanol and water at equilibrium (logP ow). Higher values indicate
ly higher for placebo than for active treatgreater lipid solubility. [ACD calculation - ChemSpider]
ment.12
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, irritation, dryness, and folliculitis. Cloderm
Cream is contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
Supported by Promius Pharma, LLC.
Case Report
1a
1b
2a
2b
Photos courtesy of Joseph Bikowski, MD/DermEdOnline.com
In the trial designed to determine the influence of
Cloderm Cream on HPA-axis suppression, healthy
male subjects applied 30g of clocortolone pivalate
cream 0.1% twice daily (for a total application of 60
grams) under occlusion. Occlusion was provided via
plastic suits worn for 12 consecutive hours each day.
No evidence of adrenal suppression (as determined
by plasma cortisol) was seen over the 21-day trial
period.12
Cloderm Cream can be used in combination with
other therapies, including topical calcineurin
inhibitors (TCIs). Combination therapy has been
widely used in clinical practice and recently has been
documented as effective in the literature. In one
study, concomitant treatment with Cloderm Cream
and tacrolimus ointment 0.1% produced significant
improvement in dermatologic sum scores at days 14
and 21. Combination therapy was effective for measures of excoriation and induration at day 21 and erythema at day 14. The effectiveness of this combination treatment was seen early on, for excoriation at
days 7 and 14, oozing or crusting at days 3 and 7, and
lichenification at day 3.13
Clinical Applications
The moisturizing cream vehicle base of Cloderm
Cream consists primarily of water and emollient ingredients, such as white petrolatum, mineral oil, and
stearyl alcohol. This non-greasy cream vehicle is dispensed in either a tube or pump. There is no difference
in the vehicle formulation in the tube or pump; the
A 33-year-old female patient presented with pruritic, erythematous,
same cream is contained in either dispenser.
scaling lichenified patches on the lateral aspects of the antecubital
Either dispenser may provide unique benefits in fossa (1a), the axillary vaults (2a), inframammary area, and about the
specific settings. For example, when the prescriber is neck. The patches had been present for about three months, and the
concerned that a patient may over- or under-apply a patient rated the degree of pruritus as 10 on a 10-point scale. Mild erythema and scaling were noted on the eyelids and face.
topical corticosteroid, the pump may be preferred. It
The patient was otherwise in good health, and the past medical history
dispenses a consistent “dose” of corticosteroid with
was non-contributory. The patient was diagnosed with a flare of atopic
each pump, and the prescriber may instruct the dermatitis and was directed to apply Cloderm Cream to all affected
patient on the number of pumps to apply to any areas, including the eyelids and face, twice daily.
given anatomic site. (See Fig. 3 for information on The choice of Cloderm Cream was based on the desire to use a middosing.) The pump may also be suitable for parents potency topical corticosteroid for application to the “thinner” skin of
concerned about possibly over-applying corticos- the eyelid, axillary vaults, and inframammary area. Additionally, a cream
formulation was preferred for easy application and cosmetic acceptabilteroids on children, or when the prescriber worries ity at these various body sites. A 90-gram tube was prescribed to
about potential non-compliance. The pump simpli- ensure adequate medication for the large total area of involvement.
fies the regimen, there is no mess, and no cap to At one-week follow-up, marked improvement of symptoms was seen
replace. The flexible dosing of the tube may be pre- (2a, 2b). Pruritus had decreased to a score of 2 out of 10. The patient
ferred for other patients, including those with large reported high satisfaction with therapy. She was advised to apply
Cloderm Cream twice daily as needed if any sign of a flare was seen
surface areas of involvement. Providing enhanced and was scheduled for follow-up in one month.
therapeutic control and potential convenience,
Cloderm Cream is available in four different sizes: the pump ments. The selection of an appropriate vehicle depends on
is available in the 30g and 75g size, while the tube is avail- numerous factors, and novel vehicles may be particularly useful for certain applications, such as treatment of the scalp.
able in 45g and 90g.
Formulation advancements in recent years have led to new Nonetheless an effective, moisturizing cream-based formulacorticosteroid vehicles on the market, including foams, gels, tion remains an important option for a vast number of patient
and sprays, in addition to creams, lotions, solutions, and oint- presentations. (See Case Report.)
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, irritation, dryness, and folliculitis. Cloderm
Cream is contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
Supported by Promius Pharma, LLC.
Conclusion
Fig. 3. Cloderm Cream Pump
Estimated Coverage Amounts
Adult Coverage
Face and neck
7
2.5
pumps
pumps
Trunk: Front or back
1 Arm
3
pumps
1
pump
1 Hand
6
2
pumps
pumps
1 Leg
1 Foot
1 pump application equals approximately 1 fingertip unit.
Clinical Applications
Low-to-mid potency steroids are prescribed when necessary
for treatment of the face, axillae, or intertriginous areas, where
thinner, more sensitive skin is associated with an increased susceptibility to common corticosteroid side effects. In my practice, I have prescribed Cloderm Cream for treatment of various
sites. I have even prescribed the formulation for eyelid dermatitis. Data suggest topical corticosteroids can be used safely in the periorbital region;14 choice of a low- or mid-potency
corticosteroid seems reasonable for such application.
Because, as noted, the risk for developing adverse
events associated with topical corticosteroids increases as
the potency of the drug or the duration of therapy increases, it is still widely acknowledged that topical corticosteroid use should be limited to short durations. However,
many of the inflammatory dermatoses that respond to topical corticosteroids are chronic in nature, with relapsing
remitting courses. As such, many patients require longterm maintenance therapy or “pulse therapy,” aimed at
periodic exacerbations of disease. For long-term and/or
intermittent use, a low-to-mid potency corticosteroid, such
as Cloderm Cream is preferred over more potent steroids.
In the case of the Cloderm Cream pump, the additional
control over dosing provided by the pump dispenser helps
to ensure that patients do not over-use or misuse the corticosteroid over the long term.
Topical corticosteroids remain a cornerstone of dermatologic care, with potential use for a wide range of inflammatory
skin diseases. Though topical corticosteroids are historically
associated with certain adverse effects that necessitate judicious use, the clinical reality is that within an appropriate
regimen, they can be used to relieve inflammation and pruritus associated with acute and chronic dermatoses with an
excellent safety profile.
The unique formulation of Cloderm (clocortolone
pivalate) Cream 0.1% provides an important therapeutic
option that may be suitable for many patients with steroidresponsive dermatoses. The specially engineered molecule
balances needed potency and documented efficacy with a
favorable safety profile. The lipophilic molecule absorbs
quickly into the epidermis, contributing to a rapid onset of
therapeutic effect.
The moisturizing cream base is elegant, providing emollient benefits that are desirable in many chronic dermatoses.
The availability of two dispensing systems—a tube and a
pump—allows clinicians to best match treatment to the
needs of the patient and allows greater control of treatment.
Effective with an excellent safety profile for the treatment of atopic dermatitis, eczema, psoriasis, contact dermatitis, and other steroid-responsive dermatoses, Cloderm
Cream is a versatile therapy in the dermatologist’s armamentarium. ●
Dr. Bikowski is a consultant for and has served on the Advisory
Board and Speakers Bureau for Promius Pharma, LLC.
1. Datamonitor, Dermatology Market Report 2007. DataMonitor.com, accessed
May 18, 2011.
2. Goa KL. Clinical pharmacology and pharmacokinetic properties of topically
applied corticosteroids. A review. Drugs. 1988;36 Suppl 5:51-61.
3. Hengge UR, Ruzicka T, Schwartz RA, Cork MJ. Adverse effects of topical glucocorticosteroids. J Am Acad Dermatol. 2006 Jan;54(1):1-15
4. Weber G. Perioral dermatitis, an important side-effect of corticosteroids.
Dermatologica. 1976;152 Suppl 1:161-72.
5. Chen AY, Zirwas MJ. Steroid-induced rosacealike dermatitis: case report and
review of the literature. Cutis. 2009 Apr;83(4):198-204.
6. Moss GP. Nomenclature of Steriods. Pure & APPL Chem. 1989. 51(10):17831822
7. Bikowski J, Pillai R, Shroot B. The position not the presence of the halogen
in corticosteroids influences potency and side effects. J Drugs Dermatol. 2006
Feb;5(2):125-30.
8. Siddiqui O, Roberts MS, Polack AE. Percutaneous absorption of steroids: relative contributions of epidermal penetration and dermal clearance. J
Pharmacokinet Biopharm. 1989 Aug;17(4):405-24.
9. Katz M, Gans EH. Topical corticosteroids, structure-activity and the glucocorticoid receptor: discovery and development--a process of "planned serendipity". J Pharm Sci. 2008 Aug;97(8):2936-47.
10. ChemSpider, Royal Society of Chemistry, 2011; chemspider.com
11. Rosenthal AL. Clocortolone pivalate: a paired comparison clinical trial of a
new topical steroid in eczema/atopic dermatitis. Cutis. 1980 Jan;25(1):96-8.
12. Data on file, Promius Pharma, LLC.
13. Torok HM, Maas-Irslinger R, Slayton RM. Clocortolone pivalate cream 0.1%
used concomitantly with tacrolimus ointment 0.1% in atopic dermatitis. Cutis.
2003 Aug;72(2):161-6.
14. Haeck IM, Rouwen TJ, Timmer-de Mik L, et al. Topical corticosteroids in
atopic dermatitis and the risk of glaucoma and cataracts. J Am Acad Dermatol.
2011 Feb;64(2):275-81.
Cloderm® is a trademark of Coria Laboratories, Ltd.
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, irritation, dryness, and folliculitis. Cloderm
Cream is contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
™
www.the-dermatologist.com
September 2011
Get Reacquainted With
Clocortolone Pivalate
A review of how its molecular structure and
high lipid solubility make this a unique
mid-potency topical corticosteroid.
Supported by
Get Reacquainted With Clocortolone Pivalate
A review of how its molecular structure and high lipid solubility make this
a unique mid-potency topical corticosteroid.
Leon Kircik, MD
lthough topical corticosteroids are effectively used to
manage common dermatologic conditions, many of
us are concerned about their adverse events. In fact,
80.7% of respondents to one survey said they had fears
about using topical corticosteroids, and 36% acknowledged
they had not adhered with topical corticosteroid therapy
due to safety concerns.1 This despite the excellent safety
profile of topical corticosteroids when used properly.
Patients may think corticosteroids are virtually interchangeable, but there are many formulations, potencies and safety profiles.While all members of the corticosteroid class have common
characteristics — because all are chemically engineered from
hydrocortisone — the reality is that each topical corticosteroid
formulation has unique features based on its exclusive molecular
structure and essential features of its vehicle base.
To enhance patient confidence in therapy and potentially encourage therapeutic adherence, physicians must
understand key concepts regarding corticosteroid safety
and efficacy in order to select the appropriate corticosteroid for their patients. They must also be prepared to
educate patients about these features.
The mid-potency topical corticosteroid clocortolone
pivalate 0.1% cream (Cloderm ® Cream) (Promius
Pharma, LLC) provides a useful example for addressing
the influence of molecular structure, vehicle formulation, potency and safety on the patient experience.
A
ENGINEERING THE MOLECULE
Topical corticosteroids are primarily anti-inflammatory, acting on mediator release and function, inflammatory cell function and release of lysosomal enzymes.2
Corticosteroids are 21-carbon compounds with a 2-carbon side chain at C-17.2,3,4 All adrenal steroids share the
same basic structure: three 6-carbon rings (A, B, C) and
a single 5-carbon ring (D). Although modifying the molecular structure may yield a variety of changes in topical
corticosteroid characteristics, molecular modification is
usually done to influence potency and efficacy.4
Topical corticosteroids as a class are associated with certain well-known potential adverse effects5 that increase in
incidence and severity proportionate to agent potency and
duration of use.The most frequent adverse effects associated
with topical corticosteroids include burning, itching, irritation, dryness, folliculitis, atrophy, striae, acneiform erup-
tions and purpura. Other, less common adverse effects include hypertrichosis, pigmentation alterations, delayed
wound healing and exacerbation of skin infections.5,6 Topical corticosteroids may also be associated with sensitization, which is relatively rare.2
Topical steroid potency is a source of potential confusion for patients and some clinicians. Topical corticosteroids are available across a range of potencies from 1
(superpotent) to 7 (lowest potency). Although the highest
and lowest potency topical corticosteroids are important
in managing dermatologic diseases, the clinical reality is
that most patients are treated with mid-potency topical
corticosteroids. Generally, mid-potency topical corticosteroids are thought to provide a favorable balance of
safety and efficacy for both short-term application and
for longer-term and intermittent use.
Clocortolone pivalate 0.1% was introduced to the market
in 1977 in a moisturizing cream vehicle base. It is an effective, upper-mid-potency (class 4) steroid formulation with
a wide range of potential clinical uses.
Among the structural modifications used to engineer
clocortolone pivalate are β-hydroxylation at C-11, methylation at C-16, double bonds at C-12, esterification at C21, and halogenation at C-6 and C-9. These structural
features of clocortolone pivalate have increased the molecule’s anti-inflammatory potency and lipophilicity and,
subsequently, its penetration.
The medical community has somewhat misunderstood
the effects of halogenation on a corticosteroid molecule.
Certain halogenated high-potency corticosteroids have
been associated with increased rates of significant adverse
effects, leading clinicians to associate halogenation with reduced safety. However, the chemistry behind corticosteroids
shows that this is a misperception.5
Halogen atoms in themselves don’t increase the incidence
of adverse events associated with topical corticosteroids.
Rather, the position and nature of the halogen atoms mediate
the potency of the molecule and the incidence of adverse
events.5 The halogen atoms in clocortolone pivalate are chlorine at C-9 and fluorine at C-6 — a unique feature of the
molecule not found in any other corticosteroid.These modifications produce a corticosteroid in the upper-mid-potency
range, but with a safety profile associated with a much lowerpotency molecule, as discussed below.
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, dryness, and folliculitis. Cloderm Cream is
contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
2
September 2011 • S u p p l e m e n t t o S k i n & A g i ng
Get Reacquainted with Clocortolone Pivalate
however halogenation at C-6 or C-9 is shown to enhance
receptor affinity and may counter reduced binding due to
the molecules’ size.11
Safety
Figure 1. Structural modifications associated with improved
anti-inflammatory activity and improved percutaneous penetration (left) compared to steroid nomenclature (right).
Source: Promius Pharma, LLC
Figure 2. Partition ratios of commonly used mid-strength
topical corticosteroids. The partition ratio represents the
concentration of drug in each phase of an immiscible mixture of octanol and water at equilibrium (logP ow). Higher
values indicate greater lipid solubility.
Source: Advanced Chemistry Development, Inc., chemical database.
The clocortolone pivalate molecule’s unique features make
it highly lipophilic, which is an important characteristic of
topical steroids. Esterification at C-21 with substitution of the
pivalate group is linked directly to increased lipid solubility,
duration of action and potency. Additionally, adding methyl
groups helps increase lipid solubility. In fact, clocortolone pivalate has the highest lipid solubility of many commonly used
mid-strength topical corticosteroids (See Figure 1).7
High lipid solubility is associated with increased absorption and penetration of drugs through the stratum
corneum.2 This may explain why highly lipophilic topical
corticosteroids are shown to achieve higher concentrations
in the viable epidermis and thus exhibit greater anti-inflammatory potency.8,9 Percutaneous absorption studies confirm
that, compared with less lipophilic molecules, the most lipidsoluble corticosteroids were better delivered, penetrated the
stratum corneum at the fastest rates, and exhibited the highest epidermal concentrations.8,9 (See Figure 2.)
The large size of the pivalate group would be suspected
to somewhat reduce glucocorticoid receptor affinity,10
Cloderm Cream was uniquely designed to provide
upper-mid-level potency with an excellent safety profile in
order to present a favorable treatment option for a wide
range of patients. Per the prescribing information, the use
of clocortolone pivalate 0.1% cream has no age restrictions.
As suggested above, a lipophilic molecule such as clocortolone pivalate is expected to absorb rapidly and accumulate
in the viable epidermis. A study of HPA-axis suppression involved healthy male subjects who applied 30 g of clocortolone
pivalate 0.1% cream twice daily (total application of 60 g)
under occlusive plastic suits worn for 12 consecutive hours
each day. No evidence of adrenal suppression (as determined
by plasma cortisol) was seen over the 21-day trial period.12
Many of the most common steroid-responsive dermatoses that may be treated with a mid-potency topical
corticosteroid — such as atopic dermatitis (AD), eczema
and psoriasis — are relapsing in nature. One common concern is the safety of long-term topical corticosteroid use.
In an analysis of patients treated with clocortolone pivalate
0.1% cream for more than 30 days — some patients used the
drug for up to 7 months — no systemic, cumulative or delayed adverse events were related to Cloderm Cream treatment. The overall frequency and severity of adverse events
was low.12 Among patients who used Cloderm Cream longterm, or for an average of 16 weeks, only one patient reported a treatment-related adverse event. This was a case of
dryness that required no additional treatment.12 Across various Phase III trials, the rate of adverse events associated with
clocortolone pivalate therapy was low. The most common
adverse events with Cloderm Cream include burning, itching, irritation, dryness and folliculitis. No patients developed
striae or skin atrophy over the treatment period.12
As noted, corticosteroid allergy has been identified as an
emerging but infrequent phenomenon. Clocortolone pivalate is in allergy group C, betamethasone-type steroid,
and should not be prescribed to patients with a history of
group C allergies. It’s also worth noting that group C topical
steroid group is the smallest group and the least likely to
be associated with topical corticosteroid allergy.13
Formulating the Vehicle
Engineering the molecule is, of course, just one aspect
of drug development. Vehicle formulation should optimize potency by maximizing delivery at the target site
and encourage good patient adherence. The vehicle of
Cloderm Cream is moisturizing, yet non-greasy, and con-
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, dryness, and folliculitis. Cloderm Cream is
contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
S u p p l e m e n t t o S k i n & A g i ng • S e p t e m b e r 2 0 11
3
Get Reacquainted with Clocortolone Pivalate
tains the emollient ingredients, white petrolatum, mineral
oil and stearyl alcohol.
Emollient creams such as Cloderm Cream help improve epidermal barrier function.This is an important consideration in
managing steroid-responsive dermatoses such as eczematous
diseases and psoriasis.14 Occlusive emollients moisturize the skin
by replacing lipids in the stratum corneum and providing a
physical barrier that prevents evaporative epidermal water loss.
Additionally, the non-greasy emollient cream improves the skin
feel and may rapidly improve the feel of dry, eczematous skin.
The cream vehicle formulation is dispensed in either a
tube or pump. Dispensing product from a pump may be associated with more control than other dispensers. More importantly, the pump provides a consistent dose of medication,
providing prescriber and patient more treatment control.The
prescriber instructs the patient on the number of pumps of
medication to apply to any given anatomic site.
Clinical Applications and Evidence
As a class IV mid-potency topical corticosteroid, clocortolone pivalate may be used for a range of steroid-responsive
dermatoses. The hydrating cream vehicle may be especially
useful for treating eczema, atopic dermatitis and psoriasis —
all of which were investigated in successful Phase III trials.
As expected of a highly-lipophilic corticosteroid with
enhanced potency, Cloderm Cream was shown in Phase
III clinical trials, to provide a rapid onset of therapeutic effect.12 Patients with eczema and AD saw a statistically significant improvement relative to placebo at day 4. The AD
trial measured objective criteria, such as erythema, edema
and transudation; bullae and vesicles, papules, plaques, scaling, crusting, fissures and lichenification, if present; and subjective measures, such as relief of pain, itching or burning.
The frequency of adverse reactions was low.12
In psoriasis trials, active treatment with Cloderm Cream was
superior to placebo by day 7. Active therapy was shown to be
superior to placebo at days 14, 21 and 28. As in the AD study,
the rate of reported adverse events was low, and none were significant. In fact, the incidence of reported adverse events was
actually higher for placebo than for active treatment.12
Conclusion: Clinical Realities
Topical corticosteroids as a class are associated with certain
adverse events that vary in severity and incidence. The risk
for developing adverse events increases as the drug potency
or therapy duration increase. Prescribers can reduce the risk
of adverse events by selecting formulations that effectively
balance efficacy and safety. Educating patients about properly
using topical corticosteroids and describing characteristics of
the specific therapeutic agent selected may help allay patient
fears and improve therapeutic adherence.
Characteristics of a topical corticosteroid formulation that
influence its potency and safety are molecular structure, the
presence and location of halogen atoms, lipophilicity, molecule
size, and vehicle-base characteristics. The unique formulation
of clocortolone pivalate 0.1% cream (Cloderm Cream) provides a therapeutic option with a long-documented history of
efficacy and safety.
The selectively engineered molecule, which has no
generic equivalent, has a high lipid solubility, so it absorbs
quickly into the epidermis and confers a rapid onset of
therapeutic effect, as demonstrated in clinical trials.12 The
moisturizing, cosmetically elegant cream base delivers
emollient benefits. As a class IV mid-potency steroid, Cloderm Cream is very versatile and not associated with a high
risk for HPA-axis suppression or other adverse effects.
Dr. Kircik is an advisor and consultant for
Promius Pharma, LLC. Dr. Kircik is an Associate Clinical Professor of Dermatology at Indiana University Medical Center and at Mount
Sinai Medical Center. His is also the Medical
Director of Derm Research, PLLC, and Physicians Skin Care, PLLC, in Louisville, KY.
References
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in atopic dermatitis: a study of its nature, origins and frequency. Br J Dermatol. 2011
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7. Bikowski J. Clinical Insights. Clocortolone pivalate cream 0.1%: a versatile treatment option for a range of common dermatoses. Practical Dermatology. 2011:8(7).
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contributions of epidermal penetration and dermal clearance. J Pharmacokinet Biopharm. 1989;17(4):405–424.
9. Magnusson BM, Cross SE, Winckle G, Roberts MS. Percutaneous absorption
of steroids: determination of in vitro permeability and tissue reservoir characteristics in human skin layers. Skin Pharmacol Physiol. 2006;19(6):336–342.
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size as revealed by the bilinear LinBiExp model. Steroids. 2008;73(2):193–208.
12. Cloderm Cream [data on file]. Bridgewater, NJ: Promius Pharma; 2011.
13. Baeck M, Chemelle J, Rasse C, el Terreux R, Goossens A. C16-methyl corticosteroids are far less allergenic than the non-methylated molecules. Contact Dermatitis. 2011; 64(6):305–312.
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in eczema and other dry skin conditions. J Dermatolog Treat. 2002;13(3):103–106.
Cloderm® is a trademark of Coria Laboratories, Ltd.
Important Safety Information. The most common adverse events with Cloderm Cream include burning, itching, dryness, and folliculitis. Cloderm Cream is
contraindicated in patients who are hypersensitive to any of the ingredients of this product. As with all topical corticosteroids, systemic absorption can
produce reversible HPA-axis suppression. For more information and full prescribing information please visit www.cloderm.com or see accompanying PI.
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September 2011 • S u p p l e m e n t t o S k i n & A g i ng
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