Effective Over-the-Counter Acne Treatments

Whitney P. Bowe, MD, and Alan R. Shalita, MD

Acne is the most common disease of the skin, yet only a fraction of acne sufferers are
treated with prescription products by physicians. There is, however, a large and expanding
market for over-the-counter (OTC) medications, many of which are not only effective but
also well tolerated and cosmetically elegant. Given the presence of OTC acne medications
on the television, the Internet, and store shelves, patients will be acutely aware of these
OTC remedies and will have questions. Patients will expect dermatologists to advise them
regarding products to use either as a sole therapy or in combination with prescription
drugs. Recently, combinations of OTC acne medications in treatment regimens or kits
have gained popularity and appear to have increased patient compliance. Quality-of-life
outcomes from OTC medication use, in at least one study, have demonstrated good benefit.
The most common OTC ingredients include benzoyl peroxide, a potent antibacterial agent,
and salicylic acid, a mild comedolytic and antiinflammatory medication. Other, less-common OTC ingredients include sulfur, sodium sulfacetamide, and alpha hydroxy acids. Zinc,
vitamin A, tea tree oil, and ayurvedic therapies also are available OTC for acne. Additional
and better studies are needed to clarify the benefit of these latter medications.
Semin Cutan Med Surg 27:170-176 2008 Published by Elsevier Inc.

ore than 85% of teenagers are afflicted with acne,1 and

42.5% of men and 50.9% of women continue to suffer
from this disease into their 20s.2 Although the peak prevalence of acne is in the teenage years, the mean age at presentation for treatment is 24 years.3 Before scheduling that initial
evaluation with a physician, teenagers and young adults will
frequently seek over-the-counter (OTC) remedies for their
acne. It is not uncommon for patients to return to these
therapies after experiencing side effects from prescription
therapies, or even to use OTC products in combination with
prescription acne therapies.
Prescription antiacne product sales have been stable or
growing slowly, whereas OTC sales have been increasing in
recent years.4 The global market for prescription antiacne
products reached US $2.0 billion in 2001 and was forecast to
reach revenues of US $3.3 billion in 2006 The nonprescription market world wide is estimated to be anywhere from 2 to
4 times the size of the prescription market, making the consumer acne market one of the fastest-growing segments of the
dermatological industry. With products lining the shelves of
pharmacies, department stores (eg, Nordstrom), and cosmetic counters (eg, Sephora), OTC therapies are readily
available and usually even come dermatologist-recommended. Several product lines are developed by dermatol-

Department of Dermatology, SUNY Downstate Medical Center, Brooklyn, NY.

Address reprint requests to Whitney P. Bowe, MD, 450 Clarkson Avenue,
Brooklyn, NY 11203. E-mail: wpbowe@gmail.com

170

1085-5629/08/$-see front matter 2008 Published by Elsevier Inc.

doi:10.1016/j.sder.2008.07.004

ogists themselves and either marketed with their name (eg,

Wexler, Brandt, etc) or marketed over television. Proactiv, an
OTC acne kit developed by dermatologists and advertised via
infomercials, grossed more than $600 million in 2007 Not
only are OTC products ubiquitous and heavily advertised,
but they may even be viewed as safer than prescription drugs
by pregnant women, lactating women, and parents of young
children. In parts of the country where there is a long wait
time for a dermatology appointment, many patients also may
seek out OTC medications as a first-line therapy. Patients
seeking information on acne treatment on the Internet commonly encounter websites touting the benefits of OTC medications. Furthermore, many of these sites mislead the consumer with statements such as Your dermatologist should
only be seen as a last resort, as many prescription strength
acne treatments will affect your kidneys and can lead to long
term health problems (http://www.thehealthcarecenter.
com/acne_treatment.html).
It is essential for dermatologists to be aware of effective
(and ineffective) OTC products for several reasons. Given the
presence of OTC acne medications on the television, Internet, and store shelves, patients will be acutely aware of these
OTC remedies and will have questions. Patients will expect
dermatologists to advise them regarding products to use either as a sole therapy or in combination with prescription
drugs. Knowledge of active ingredients in, and the efficacy of,
common OTC therapies (Table 1) will aid with history-taking and appropriate therapeutic selection. If prescription

Effective OTC acne treatments

171

Table 1 Relative Efficacy of Topical Acne Products

Benzoyl peroxide
Salicylic acid
Combinations

Inflammatory

Noninflammatory

an undetectable film of medication remains on the skin subsequent to rinse-off. Systemic absorption of topical products
increases with increased surface area of contact, application
to a disrupted skin barrier, duration, and frequency of application.6

Benzoyl Peroxide
products are recommended, dermatologists must be capable
of explaining why these products are superior to OTC alternatives. Finally, a physician should be able to advise which
OTC products must be discontinued during therapy while
recognizing which products best complement the prescribed
therapeutic regimen.
OTC therapies might be more cosmetically elegant, accessible, strategically advertised, less expensive, and less irritating than prescription therapies. However, the question remainsjust how effective are these products? The purpose of
this review is to discuss the efficacy of currently available
OTC acne treatments and to introduce some potential future
OTC acne therapies in development.

General Principles
OTC drugs may be sold without a prescription and without a
visit to a medical professional. In the United States, the manufacture and sale of OTC substances is regulated by the Food
and Drug Administration (FDA). In order for a drug to be
sold OTC, it must primarily be used to treat a condition that
does not require the direct supervision of a physician and
must be proven to be reasonably safe and well-tolerated, with
little or no abuse potential. Over time, drugs that prove themselves safe and appropriate for self-medication may be
switched from prescription to OTC.
Most dermatological OTC products are designed for topical application. One clear advantage of topical preparations is
local application to the affected area, thereby maximizing
exposure to the pilosebaceous units while minimizing systemic absorption (Table 2). However, if the drug is formulated such that it cannot penetrate the pilosebaceous unit
(secondary to molecular size or hydrophylicity), the active
ingredient will merely sit on the skin surface without ever
reaching its target. In this case, these drugs may have impressive in vitro study results that may never translate to clinical
efficacy.
OTC topical products come in a variety of strengths and
formulations. As with topical prescription products, formulations include gels, pledgets, washes, solutions, lotions, and
creams. Creams and lotions are preferable for patients with
dry, easily irritated skin,5 whereas the other formulations can
be drying and are particularly suited for oily skin.
The main side effect of topical products is irritation. Dermatologists frequently discourage patients from applying
anything to their faces other than what is prescribed so as to
minimize irritation.5 Increased irritation will result from
more liberal or more frequent application of a drug. Cleansers and masks are washed off after transient application.
However, some washes demonstrate substantivity, meaning

The medical use of benzoyl peroxide (BPO) began in the

1960s as a treatment for leg ulcers and decubitus ulcers. It
was first used for the treatment of acne in 1979 BPO is a
potent topical bactericidal agent commonly used as a firstline therapy for the treatment of acne. It reduces the population of Propionibacterium acnes by generating reactive oxygen
species within the sebaceous follicle.7 Effective against both
inflammatory and noninflammatory lesions, BPO improves
acne as early as 5 days after the initiation of treatment.5 BPO
is available in a wide variety of preparations, including
cleansers, lotions, creams, gels, and pads. Reduction of
P. acnes is greater with leave-on products rather than with
washes but both will significantly reduce P. acnes and lesion
counts. Prescription and OTC products contain anywhere
from 2.5% to 10% BPO. The sale of OTC BPO far exceeds
that of other OTC acne therapies.8
When compared with other topical antimicrobials, 5%
BPO was found to be at least as effective for acne as erythromycin9 and clindamycin formulations.10,11 Importantly, BPO
has the ability to prevent or eliminate the development of
P. acnes resistance12-17 and is therefore an ideal adjunct to
topical or oral prescription antibiotic therapy. Fixed-combination products containing BPO and a topical antibiotic
(Benzaclin, Dermik Laboratories, Inc., Berwyn, PA; Duac,
Stiefel Laboratories, Inc., Duluth, GA; Benzamycin, Dermik
Laboratories) are more effective for acne than BPO or the
topical antibiotic alone. In this regard, a patient who reports
improvement with an OTC BPO product might benefit even
further by replacing this product with a prescription combination product. Researchers from Englands universities of
Nottingham and Leeds found that topical BPO was similar in
efficacy to oral minocycline,18 which is widely considered the
most potent oral antibiotic therapy for acne. However, this
finding has never been confirmed and this study was limited
to patients with only mild to moderate acne.
Interestingly, 10% BPO has never been shown to be more
effective than the 5% concentration. Furthermore, 2.5%
BPO, in at least one study, was found to be equivalent in
antibacterial efficacy to 10%.8 Therefore, with regard to BPO,
more is not necessarily better. Although efficacy does not
appear to increase with concentration, side effects do. For
those whose skin is more sensitive to the drying, peeling, and

Table 2 Common OTC Ingredients

Benzoyl peroxide
Salicylic acid
Sulfur
Sodium Sulfacetamide
Alpha hydroxy acids

W.P. Bowe and A.R. Shalita

172
erythema caused by BPO, prescription 2.5% BPO might be
more suitable, offering an equally effective but less irritating
alternative.
Irritation is the most common side effect experienced with
BPO use. This irritation may take the form of erythema, dryness, peeling, stinging, or burning. This discomfort will increase with increasing concentration and frequency of use.
Contact sensitization, however, may occur in up to 2.5% of
patients,19 and will occur with any concentration as soon as
the patient is sensitized.
Vehicles may also be important in influencing the efficacy
and side effects of BPO. Some OTC BPO products claim that
the vehicle in which the BPO is delivered significantly enhances compliance by creating a cosmetically elegant product that also minimizes irritation (Proactiv, or the prescription BPO, Brevoxyl [Stiefel]). BPO is a Pregnancy Category C
drug. Although it is not specifically FDA approved for pediatric use, its OTC status makes such use inevitable.

Salicylic Acid
Salicylic acid (SA; from Salix, the Latin word for the willow
tree) is a phytohormone, a plant product that acts like a
hormone by regulating cell growth and differentiation. It is a
beta hydroxy acid that is chemically similar to the active
component of aspirin. It functions as a topical desquamating
agent, dissolving the intercellular cement holding the cells of
the stratum corneum together.20 Because SA is also lipid soluble (unlike alpha hydroxy acids), it is able to penetrate the
pilosebaceous unit and have a comedolytic effect. Although
SA has been used for many years in the treatment of acne and
is found in a variety of OTC acne remedies (particularly
cleansers), few well-designed clinical trials of its safety and
efficacy exist. It is considered moderately effective in the
treatment of acne,21 and its comedolytic properties are considered less potent than topical retinoids. Therefore, SA is
used by dermatologists when patients cannot tolerate topical
retinoid, or benzoyl peroxide therapy because of skin irritation,22,23 or as adjunctive therapy to other, more effective,
medications.
Concentrations of SA ranging from 0.5% to 10% have been
used for the treatment of acne,24,25 but concentrations of 3%
to 6% are more commonly reserved for hyperkeratotic skin
disorders (eg, psoriasis, ichthyoses, keratosis pilaris, etc)26
and 5% to 40% concentrations are used for wart and corn
removal. The maximum strength of SA permitted in OTC
acne products in the United States is 2%. SA is an FDA
Pregnancy Category C drug, and the safety of SA consumption by nursing mothers is unknown. It is, however, approved for use in pediatric acne.
Although SA is generally considered to be a less-potent
agent in the treatment of acne when compared with BPO, at
least 2 studies contradict this assumption. In a study submitted to the FDA in 1982, one of us (ARS) demonstrated the
superiority of 2% SA alcoholic detergent solution (Stridex) as
compared with BP 5% cream.27 It was later found that patients treated with a 2% SA cleanser for 2 weeks showed a
significant improvement in acne but worsened when using a

10% benzoyl peroxide wash during the following 2 weeks.28

In both instances, we believe the superiority can be attributed
to better compliance with SA because of less irritation. Furthermore, BPO and SA may best be used in combination as
part of a complete skin care regimen, as they have two different mechanisms of action that appear to complement one
another in the treatment of acne.
Interestingly, SA acne therapy might provide a fringe benefit: protection from sun damage. The antiinflammatory
properties of SA are not surprising, given its close chemical
relationship to one of the most well-known antiinflammatory
drugs available, acetylsalicylic acid (aspirin). SA has been
shown to inhibit UVB-induced sunburn cell formation, as
well as increase the removal of UVB-induced TT dimer formation in living skin equivalents.29
SA is likely to cause local skin peeling when used at concentrations of 2% or greater. The greater the concentration
used, the greater the risk of causing hyperpigmentation in
those with darker skin types (Fitzpatrick phototypes IV, V,
VI). Percutaneous absorption of SA is rather efficient compared with most other topical agents, even by normal skin.30
The bioavailability increases further in diseased skin,31 with
prolonged duration of contact6 and with certain vehicles such
as mineral oil and petrolatum.30 Possible adverse events may
be observed with application of the drug to a large body
surface area for prolonged periods of time,6 including salicylate toxicity, toxic inner ear damage, hypoglycemia, and
hypersensitivity.26,32 Although there are multiple reports
of acute salicylate intoxication as a result of topical SA
use,31,33-38 none of these incidents resulted from therapies
specifically marketed for acne.

Sulfur
The chemical element sulfur has been used to treat acne for
decades. It is a yellow, nonmetallic element with mild keratolytic, antifungal and bacteriostatic properties.39,40 Its precise mechanism of action is unknown. When in contact with
keratinocytes, sulfur is thought to interact with cysteine in
the stratum corneum, thereby reducing sulfur to hydrogen
sulfide.41 Hydrogen sulfide is then capable of degrading keratin, hence the keratolytic activity of sulfur. The smaller the
particle size of sulfur, the more interaction that can occur
with keratin and, hence, the greater the efficacy.41 Sulfur is
found in OTC and prescription topical acne products, with
concentrations ranging from 1 to 10%. It may be found in
lotions, creams, soaps and ointments.
Efficacy appears to increase when sulfur is combined
with benzoyl peroxide42,43 and sodium sulfacetamide,44
and sulfur is also found in combination with resorcinol or
salicylic acid. One study showed that sulfur was comedogenic when applied to human and rabbit skin,45 but contrary results have been found in a subsequent doubleblind, randomized study.46,47 Side effects are rare, mainly
limited to malodor and dry skin.41 Although older sulfurcontaining formulations were effective, their application
was time consuming, messy, and they were associated
with an unpleasant odor (eg, Vleminckx solution, Ress

Effective OTC acne treatments

solution).48 Newer preparations appear to be cosmetically
acceptable, prompting some authors to reconsider sulfurs
minimal role in our acne armamentarium.46 Only 1% of
topically applied sulfur is systemically absorbed, but fatal
outcome after extensive application to infant skin has been
reported.41 Patients with sulfonamide sensitivity may generally use elemental sulfur without concern.49

Sodium Sulfacetamide
Sodium sulfacetamide is a sulfonamide capable of inhibiting
P. acnes proliferation. Sulfonamides act through competitive
antagonism of para-aminobenzoic acid, halting bacterial
DNA synthesis. A 10% concentration of sodium sulfacetamide is commonly combined with 5% sulfur in topical acne
suspensions, lotions, cleansers, and creams. This combination has been shown to reduce both inflammatory lesions and
comedones.44,50 It also appears to be cosmetically appealing,
showing only mild transient dryness and itching44,50 as well
as synergistic.51
Percutaneous absorption through human cadaver skin is
estimated at 4%.39,50 Adverse reactions are infrequent and
usually restricted to pruritus or erythema at the application
site. Generally, sodium sulfacetamide is considered less irritating than benzoyl peroxide and retinoic acid.50,52 Rare
cases of erythema multiforme53 and StevensJohnson syndrome50,54,55 have been reported after topical ophthalmic use.
Topical sodium sulfacetamide is contraindicated in patients
with a sulfa allergy, as hypersensitivity can occur following
re-administrations of sulfa by any route.49,55 Sodium sulfacetamide is also avoided in patients with a sulfonamide allergy, as sulfa and sulfonamides are thought to cross-react.

173
and re-epithelization process.61 There appears to be a synergistic lightening effect when these 2 agents are combined.

Zinc
Zinc is a metallic chemical element that is crucial for the
normal development and physiology of human skin.62 Approximately 6% of total body zinc is found in the skin.63 In
the 1970s, Fitzherbert64 first reported improvement of acne
on oral zinc supplementation of zinc in zinc-deficient patients. Serum zinc levels in patients with acne were found to
be low,65,66 and oral zinc was subsequently reported to be
effective in the treatment of severe and inflammatory
acne,67-73 moreso than mild or moderate acne.74,75 Zinc is
bacteriostatic against P. acnes, inhibits chemotaxis, and may
decrease tumor necrosis factor- production. Despite these
promising effects, oral doses used in these studies (200 mg of
zinc gluconate per day, 400 or 600 mg of zinc sulfate per
day) were associated with nausea, vomiting, and diarrhea.13,69,70,73,75 Gastrointestinal side effects can be ameliorated somewhat by ingesting zinc directly after meals. One to
two milligrams of copper supplementation may be recommended with long-term zinc therapy to prevent copper deficiency, because zinc decreases the absorption of copper. Oral
zinc salt supplementation has been shown to be equally or
less effective than oral tetracyclines.68,76-83 One study, however, showed that oral zinc sulfate had no effect on male
patients with moderate acne after 8 weeks of therapy, despite
evidence of systemic absorption.74 Limited efficacy and poor
patient compliance caused by gastrointestinal side effects
limit the use of oral zinc for the treatment of acne. Further
trials need to be conducted to assess the efficacy and side
effects of lower doses of oral zinc.

Alpha Hydroxy Acids

Alpha-hydroxy acids (AHAs) are weak organic acids that can
be found in fruits, milk sugars, and plants. Glycolic acid
(from sugar cane) and lactic acid (from milk) are 2 types of
AHAs found in OTC acne products, but these AHAs are often
chemically synthesized rather than isolated from natural
sources. At low concentrations, AHAs decrease corneocyte
cohesion in the lower layers of the stratum corneum, thus
possessing exfoliative capabilities.56 Not only do AHAs thin
the stratum corneum, but they also promote epidermolysis,
disperse basal layer melanin, and increase collagen synthesis
within the dermis.57 Thus, they may play a role in acne prevention as well as treatment of postinflammatory hyperpigmentation. AHAs are available OTC in concentrations up to
10%. They may be found in the form of washes, creams,
lotions and peel kits.
A number of studies have demonstrated the safety and
efficacy of a combination glycolic acid/retinaldehyde preparation,58-60 as well as its ability to complement common
topical antiacne therapies.58 Furthermore, this combination
appears to prevent and heal postinflammatory hyperpigmentation associated with acne.61 Retinaldehyde, a precursor of
retinoic acid, has shown depigmenting activity whereas glycolic acid decreases excessive pigmentation by a wounding

Vitamin A
The naturally occurring form of vitamin A is also known as
retinol. Retinol is transformed into numerous metabolites,
including retinoic acid (aka tretinoin, the active ingredient in
Retin-A, Tretin-X, and others). It is widely used in toiletries
and cosmetics as a GRAS (ie, generally recognized as safe)
ingredient. Most OTC retinol products contain between
0.04% and 0.07% retinol.
Theoretically, topical retinol should have a similar mechanism of action as its metabolite, tretinoin, in the treatment of
acne.Unlike tretinoin, retinol oxidizes very rapidly and is
inactivated by ultraviolet light. Thus, OTC preparations containing retinol may demonstrate a wide range of activity.
Some delivery systems have been developed to enhance the
stability and topical absorption of the molecule. Topical retinol is primarily touted to diminish the appearance of fine
lines and wrinkles, and even skin tone. Although often considered beneficial in the treatment of acne, there are no published, peer-reviewed clinical studies demonstrating antiacne
effects. Oral vitamin A (retinol) has been shown to benefit
acne when used in high doses (300,000 units daily for
women, 400,000 to 500,000 units daily for men).84 Adverse
events were limited to xerosis and cheilitis.

W.P. Bowe and A.R. Shalita

174

Tea Tree Oil

Tea tree oil is an essential oil of the Australian native tree
Melaleucaalternifolia. It has been used as a topical antiseptic
agent in Australia for decades and has been shown to display
a variety of antimicrobial activities. The efficacy of topical tea
tree oil as a therapy for acne has been evaluated in one singleblind, randomized clinical trial of 124 patients. In this trial,
5% tea tree oil gel significantly reduced both inflammatory
and noninflammatory acne lesions. When compared with
5% benzoyl peroxide lotion, the tea tree oil showed a slower
onset of action, but fewer side effects.85

Ayurvedic Therapies
In Sanskrit, ayu means life, and veda means knowledge.
Ayurveda is a 5000-year-old history Indian traditional system of medicine. Two randomized, double-blind, placebocontrolled trials were undertaken to study the effect of oral,86
and oral/topical combination,87 preparations of Ayurvedic
herbal extracts on acne. In the first study, treatment with an
oral preparation of Sunder Vati resulted in a significant reduction in lesion count and was well tolerated.88 Treatment
with the 3 other oral formulations studied failed to show any
improvement. The second study demonstrated that the combination of an oral Ayurvedic preparation and a topical
Ayurvedic, multicomponent preparation (cream or gel) was
more efficacious in treating acne than oral therapy alone.89
The topical cream showed more efficacy when combined
with the oral tablet than did the topical gel.

Other Therapies
There is no convincing evidence to support the use of vitamin
B6 (pyridoxine),90 chromium,91 or selenium92 in the treatment of acne. Several natural ingredients possess antioxidant,
antiinflammatory, and/or moisturizing properties which may
be useful additions to, or vehicles for, more effective acne
therapies. These include colloidal oatmeal, feverfew, licorice,
aloe vera, chamomile, curcumin, soy, coffeeberry, mushroom extracts, green tea, pine bark extract, vitamin E, vitamin C, and niacinamide.93-100 There is no evidence that these
natural ingredients possess any antiacne activity per se. However, their soothing, antiinflammatory effects could theoretically assist in decreasing the erythema associated with inflammatory acne, and their moisturizing properties could
potentially counter some of the drying effects produced by
more potent acne therapies.

Combination OTC Therapy

Combination treatments or regimens were proposed as a Zit
Kit in the 1980s but were not considered marketable at that
time. However, today there are currently several acne systems that are available to consumers who desire multiple,
complementary products to treat their acne. One such 3-step
system is the Proactiv Solution, developed by dermatologists
Dr. Katie Rodan and Dr. Kathy Fields. Although the main
active ingredients in the Proactiv 3 step system are none other
than 2.5% benzoyl peroxide and glycolic acid, the system has
become one of the most popular OTC acne therapies to date.

The success of the Proactiv Solution can be attributed to one,

or a combination, of the following: it was one of the first acne
systems available to consumers, providing a complete skin
care regimen for patients with acne-prone skin; consumers
were encouraged to use the products generously over their
entire faces daily for treatment as well as maintenance (in
contrast to using spot therapy only during flares, as the instructions for many other OTC products recommended).
The active ingredients of the 1 to 2-3 Proactiv Solution are
delivered in vehicles specifically designed to be cosmetically
elegant and minimally irritating.
A second acne system recently made available to consumers is the Obagi CLENZIderm M.D. System. The system is
comprised of a solubilized 5% BPO gel, a 2% SA toner, and a
2% SA cleanser. Although the CLENZIderm M.D. System has
OTC status, it is exclusively dispensed out of physicians
offices. Studies have demonstrated that this 3-step system
offers comparable efficacy (against inflammatory and noninflammatory acne) and patient satisfaction as compared with a
BPO/clindamycin prescription product.101-103 More recently,
the Johnson & Johnson companies, J&J Consumer and Neutrogena, have developed an acne treatment system consisting
of BPO and SA in a microgel complex. It has been demonstrated to be more effective than a competing system and had
beneficial quality of life outcomes.104

Conclusion
In conclusion, although acne is ubiquitous, only a fraction of
acne sufferers are treated by physicians with prescription
products. There is, however, a large and expanding market
for OTC medications, many of which are not only effective
but also well tolerated and cosmetically elegant. OTC acne
systems or kits have recently gained popularity and appear
to have increased patient compliance. BPO and SA are the
most common ingredients in OTC acne products. Other, less
common OTC ingredients include sulfur, sodium sulfacetamide, and AHAs. Oral zinc, retinol, oral vitamin A, tea tree
oil, and ayurvedic therapies are also available OTC for acne.
Additional and better studies are needed to clarify the benefit
of these latter medications.
To review, SA shows moderate activity against both inflammatory and noninflammatory lesions. A combination of
these 2 therapies, however, is a very effective treatment for
both inflammatory and noninflammatory lesions. BPO is
generally considered to be the most effective OTC ingredient
for reducing inflammatory lesions, and it shows moderate
activity against noninflammatory lesions. BPO and SA are the
2 most common ingredients found in OTC acne therapies.
Less commonly, sulfur, sodium sulfacetamide, and AHAs are
also found in OTC acne products.

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