21683B_Skin_Allergy_Pg_:Sept_Skin_2010_rar19 (2),rar.

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The Chronicle
Genetics

Bone marrow
transplant risky,
but may help
of & ALLERGY epidermolysis
P R A C T I C A L T H E R A P E U T I C S and C L I N I C A L N E W S from the W O R L D of D E R M AT O L O G Y I SEPTEMBER 2010
bullosa patients
 Small study shows
patients who received
stem cell transplant
from bone marrow had
better wound healing,
reduced blistering

Variety of
approaches B one marrow stem cell trans-
plantation may help fight a
rare genetic blistering skin
disease—but could be too risky for

to treatment any but the most severe cases,

according to a small study.
Canada Post Canadian Publications Mail Sales Product Agreement Number 40016917

may be Among seven patients with

recessive dystrophic epidermolysis
required bullosa, the six who received allo-

in 2010 See page 6

geneic stem-cell transplantation
from bone marrow saw improved
wound healing and a reduction in
blister forma-
Pediatric dermatology tion, reported
Dr. John E.
Dogs, cats have opposite Wagner, of the
University of

effects on eczema in children Minnesota in

Minneapolis,
and colleagues.
 Presence of dogs seem to lower childrens’ risk of developing eczema One of the
cohort). children with Dr. John E. Wagner
G. Epstein, an assistant professor
The longitudinal cohort study the incurable,
of clinical medicine at the
enrolled 762 infants and tested the often fatal skin blistering disease,
University of Cincinnati Medical

H aving a dog in the house- Center, and her colleagues. toddlers with SPTs for 15 aeroaller- died during preparation for the trans-
hold may help prevent gens, cow’s milk allergy, and hen’s plant. Of the remaining transplant
New definitions proposed patients, one child had a severe regi-
children from developing egg allergy annually from ages one
Alternately, children whose SPT men-related cutaneous toxicity and
eczema, but it turns out that a cat to four—636 completed the annual
was positive for cat allergy but another died 183 days afterward
in the house may make eczema visits to the four-year endpoint.
lived with a cat before their first
even worse, researchers have Parents’ home environments were from graft rejection and infection,
year had a significantly higher rate
found. assessed before the end of the Dr. Wagner’s team reported in the
of eczema than those who tested
Children who have lived with a child’s first year through the mea- Aug. 12 issue of the New England
positive but didn’t live with a cat
dog since before age one and test and those who tested negative on surement of allergens in a dust sam- Journal of Medicine (Wagner JE, et
positive for dog allergy on a skin the SPT, the researchers reported ple from his or her primary living al: Bone marrow transplantation for
prick test (SPT) have a significantly in the Sept. 15 issue of the Journal area. recessive dystrophic epidermolysis
lower risk of developing eczema of Pediatrics (Epstein TG, et al: The study also proposed two bullosa 2010; 363:629-639).
than children who tested positive Opposing effects of cat and dog definitions for eczema a priori “Despite the potential benefits of
but didn’t live with a dog, according ownership and allergic sensitiza- Please turn to Eczema page 10 Please turn to EB patientspage 26
to the results of a study by Dr. Tolly tion on eczema in an atopic birth

Acne The Chronicle

New global assessment scale for PSORIASIS
Evidence accumulates
POST GRAD
Australian researchers
acne scar severity developed regarding relationship
between psoriasis and
evaluate three potential
options in the treatment
 Evaluation of scarring on face, trunk anxiety and depression of head lice

S TUDY DATA SUGGEST THAT THE USE OF A GLOBAL ASSESSMENT SCALE FOR
acne scar severity (SCAR-S), inclusive of the trunk and the face,
might be a practical, validated, global system for acne scar
evaluation, and one that is clinically relevant in overall severity grad-
Please turn to Acne severity scale page 28
21683B_Skin_Allergy_Pg_:Sept_Skin_2010_rar19 (2),rar.qxd 10/18/2010 4:39 PM Page 2

Handling the details with care

Comprehensive Adaptable Reliable

Covers all the bases, from Caters to your needs and The dedicated Enliven team
initial drug access and the unique needs of each is there for you and your
injection training to continued patient you treat patients, from the moment
long-term support you prescribe ENBREL®

1.877.9ENBREL (1.877.936.2735) enbrel.ca

ENBREL is indicated for reducing signs and symptoms, inhibiting structural damage progression and improving physical function
of moderately to severely active arthritis in adult patients with rheumatoid arthritis and psoriatic arthritis. ENBREL is indicated for
reducing the signs and symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis (JIA) in patients aged 4 to
17 years who have had an inadequate response to one or more DMARDs. ENBREL is indicated for reducing signs and symptoms of
active ankylosing spondylitis. ENBREL is also indicated for the treatment of adult patients with chronic moderate to severe plaque
psoriasis who are candidates for systemic therapy or phototherapy. Product Monograph available upon request.
ENBREL and Enliven are registered trademarks of Immunex Corporation.

YOUR ENBREL SUPPORT PROGRAM

21683B_Skin_Allergy_Pg_:ps 10/21/2010 10:41 AM Page 3

THE CHRONICLE of S K I N & A L L E R G Y September 2010 · 3

TOP of
the MONTH
Anxiety, depression common in
patients with psoriasis
A new study from the Archives of
Dermatology provides additional
evidence that psoriasis patients
appear to have an increased risk of
depression, anxiety, and even suici-
dal feelings . . . . . . . . . . . . . . . . . . 9
Skin infections: Vaccine enhances
therapeutic effect of basic therapies
in patients with chronic pyoderma
Data reveal that the inclusion of the
bacterial polycomponent vaccine
Immunovac in the complex treat-
ment of patients with chronic pyo-
derma promotes enhancement of
the therapeutic effect of other
basic therapy and corrects
immunologic parameters . . . . . 11
Acne research: Selective decrease
of triacylglycerols in skin surface
lipids ameliorates acne vulgaris
Also: Minimum of adverse effects
seen in study of laser for acne scar-
ring, and new research indicates
that tetracycline and doxycycline
may be associated with inflamma-
tory bowel disease. . . . . . . . . . .14
Chronicle Postgraduate
Educational Supplement
In this issue’s Postgraduate
Educational Supplement,
Australian researchers evaluate
three options for the treatment of
head lice in children, and discuss
the background of a condition that
gives parents nightmares . . . ... 17
Vol. 16, No. 6
How do cells identify the first
protein in an amino acid chain?
The human body’s ability to recycle
proteins is the fundamental building
block that enables cell growth and
development. Scientists have known
researchers have discov-
ered how cells identify the first amino
acid in a protein chain—and taken a
photograph of it (above) using X-ray
crystallography.
since the 1980s that the first protein in
the amino acid chain determines the
lifetime of the protein. Now, McGill
University Department of Biochemistry
researchers have discovered how the
cell identifies this first amino acid—
and caught it on camera.
“There are lots of reasons cells
recycle proteins—fasting, which
causes loss of muscle, growth and
remodelling during development, and
normal turnover as old proteins are
replaced to make new ones,” said
lead researcher Dr. Kalle Gehring
from McGill’s Department of
Biochemistry.
“One way that cells decide which
proteins to degrade is the presence of
a signal known as an N-degron at the
start of the protein. By X-ray crystal-
lography, we discovered that the N-
degron is recognized by the UBR box,
a component of the cells’ recycling
system.” The powerful technique can
pinpoint the exact location of atoms
and enabled the team to capture an
image of the UBR box.
Aside from representing a major
advance in the understanding of the
life cycle of proteins, the research has
important repercussions for Johanson-
Blizzard syndrome, a rare disease that
causes deformations and mental retar-
dation. This syndrome is caused by a
mutation in the UBR box that causes it
to lose an essential zinc atom. Better
understanding of the structure of the
UBR box may help researchers devel-
op treatments for this syndrome.
This research was published in
Nature Structural & Molecular Biology
and received funding from the
Canadian Institutes of Health
Research. The investigators’ video
can be found at the following link:
http://tiny.cc/vrwfp
A Message from the
Medical Editor
n this issue of THE CHRONICLE we
focus on the common and rele-
vant condition acne vulgaris. We
report everything from evidence-
based scar assess-
ment to a study of
proven therapies as
well as expert opinion
and poorly studied
therapies including
aesthetic based thera-
py with no evidence of
efficacy.
Dr. Jerry Tan, a leading Canadian
researcher in the area of acne,
rosacea, psoriasis guidelines assess-
ment, and patient decision tools pre-
sented a valid practical global system
for acne scar evaluation which will
help researchers evaluate how well
acne therapies can prevent the unde-
sired negative outcome of acne scar-
ring. In the annual acne report we see
plenty of significant downsides of our
traditional therapies such as anti
androgen and estrogen, topical and
oral retinoids as well as topical and
oral antibiotics.
It is also reported that some der-
matologists are using adjuvant thera-
py including facials, extraction, pore
cleansing, along with IPL, fractional
laser, and photo-pneumatic therapy.
There are still many unmet needs
when it comes to acne therapy, and
these new therapies will present a
unique opportunity for us to develop
the evidence that will allow us to
Please turn to Message page 27

Subscriptions: $85.60 per year in Medical Editor Editor, Cosmetic Dermatology

September 2010 • Vol. 16 No. 6
Published eight times per year by
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E-mail: health@chronicle.org
ISSN No. 1209-0581
Contents © Chronicle
Information Resources Ltd., 2010
except where noted. All rights
reserved worldwide.
The Publisher prohibits reproduc-
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Printed in Canada. The Chronicle
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Contacting The Chronicle

 READER SERVICE: To change your address, or
for questions about your receipt of the journal,
send an e-mail to health@chronicle.org with
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““Although dermatologists who care for patients with ness hours at 416.916.CHROn (2476), or toll-
free at 866.63.CHRON (24766).
psoriasis know the burden this disease creates, it is  LETTERS: We welcome your correspondence
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at the University of Pennsylvania (see page 9) righted. Please contact Mitchell Shannon for
reprint information.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 7:55 PM Page 4
ENBREL® demonstrated sustained long-term skin clearance in plaque psoriasis patients
s MEANIMPROVEMENTIN0!3)SCORESATWEEKSINANOPEN
LABELEXTENSIONTRIALWITH%."2%,
50 mg BIW [n=311]; at 3 months, 63% mean improvement in PASI scores with ENBREL 50 mg BIW
[n=311] vs. 7% for placebo [n=307; p<0.0001])1,2‡§
ENBREL has extensive experience across all indications
s YEARSIN#ANADIANPRACTICE3
s YEARSOFCLINICALEXPERIENCEWORLDWIDE3
ENBREL has a proven safety profile
s 3AFETYPROlLESIMILARTOPLACEBOINCLINICALTRIALS1
s 0LEASESEE0RODUCT-ONOGRAPHFORIMPORTANTWARNINGSREGARDINGINFECTIONSANDMALIGNANCIES
Enliven ® – supporting you and your patient by taking the time to help with patient counselling
† Quality of life (Dermatology Life Quality Index [DLQI]) significantly improved in patients treated with ENBREL vs.
placebo (p≤0.0001).¶
ENBREL is indicated for reducing signs and symptoms, inhibiting structural damage progression and improving physical
function of moderately to severely active arthritis in adult patients with rheumatoid arthritis (RA) and psoriatic arthritis
(PsA). ENBREL can be initiated in combination with methotrexate in adult patients or used alone in RA and PsA. ENBREL
is indicated for the treatment of adult patients with chronic moderate to severe plaque psoriasis who are candidates
for systemic therapy or phototherapy.
ENBREL is contraindicated in patients with, or at risk of, sepsis syndrome, such as immunocompromised and HIV+
patients and in patients with a known hypersensitivity to ENBREL or any of its components.
Serious infections leading to hospitalization or death, including sepsis, tuberculosis (TB), invasive fungal
and other opportunistic infections, have been observed with the use of TNF blocking agents including
ENBREL. Cases of TB may be due to reactivation of latent TB infection or to new infection. Patients have
frequently presented with disseminated rather than localized disease. Many of the serious infections have occurred
in patients on concomitant immunosuppressive therapy that, in addition to their underlying disease, could predispose
them to infections.
Treatment with ENBREL should not be initiated in patients with active infections, including TB, chronic or
localized infections. Administration of ENBREL should be discontinued if a patient develops a serious infection
or sepsis. Physicians also should exercise caution when considering the use of ENBREL in patients with a
history of recurring or latent infections, including TB, or with underlying conditions, which may predispose
patients to infections, such as advanced or poorly controlled diabetes. Before starting treatment with ENBREL,
all patients should be evaluated for both active and inactive (‘latent’) TB. Prescribers are reminded of the risk
of false negative tuberculin skin test results, especially in patients who are severely ill or immunocompromised.
If inactive (‘latent’) TB is diagnosed, treatment for latent TB should be started with anti-TB therapy before
the initiation of ENBREL. Patients should be monitored for the development of signs and symptoms of
infection during and after treatment with ENBREL, including the possible development of tuberculosis in
patients who tested negative for latent tuberculosis infection prior to initiating therapy. Histoplasmosis and
other invasive fungal infections are not consistently recognized in patients taking TNF blockers, including ENBREL. For
patients who reside or travel in regions where mycoses are endemic, invasive fungal infection should be suspected if
* IMS CompuScript, January 2010.
they develop a serious systemic illness.
Very rare cases of hepatitis B virus (HBV) reactivation have been reported in patients treated with TNF antagonists.
Patients at risk for HBV infection should be evaluated for prior evidence of HBV infection before initiating TNF antagonist
therapy. Patients identified as chronic HBV carriers should be monitored for signs and symptoms of active HBV infection
while on ENBREL and for several months after discontinuing ENBREL.
There have been rare reports of CNS demyelinating disorders. Prescribers should exercise caution when considering
ENBREL for patients with these disorders.
Rare cases of neutropenia, leukopenia, thrombocytopenia, anemia and pancytopenia (including aplastic anemia), some
with fatal outcomes, have been reported in patients treated with ENBREL. Exercise caution in patients who have a
previous history of significant hematologic abnormalities.
Lymphoma and other malignancies, some fatal, have been reported in children and adolescent patients
treated with TNF blockers, including ENBREL.
In clinical trials of TNF antagonists, more cases of lymphoma were seen compared to control patients. Patients with RA
or psoriasis may be at higher risk for the development of lymphoma. Non-melanoma skin cancer has been reported
in patients treated with TNF blockers, including ENBREL. Cases of acute and chronic leukemia have been reported in
association with post-marketing TNF blocker use in RA and other indications. Whether treatment with ENBREL might
influence the development and course of malignancies is unknown.
There have been post-marketing reports of worsening of congestive heart failure (CHF), with and without identifiable
precipitating factors, in patients taking ENBREL. Physicians should exercise caution when using ENBREL in patients
who also have CHF.
Adverse reactions reported in plaque psoriasis patients were similar to those in RA clinical trials. Adverse events, including
serious adverse events, occurred at a higher frequency in plaque psoriasis patients over age 65 treated with 50 mg
twice weekly. In RA patients, the most common adverse events in placebo-controlled trials were injection site reactions
(37%), infection (35%), headache (3%), dizziness (3%) and rash (3%). In RA patients, infections and malignancies
were the most common serious adverse events observed. In plaque psoriasis trials, serious infections experienced by
ENBREL-treated patients have included: cellulitis, gastroenteritis, pneumonia, abscess, osteomyelitis, viral meningitis,
myositis, fascial infection and septic shock.
Please refer to Product Monograph for complete prescribing information.
p 2ANDOMIZEDDOUBLE
BLINDPLACEBO
CONTROLLEDSTUDYOFPATIENTSWITHCHRONICSTABLEPLAQUEPSORIASISINVOLVING≥OFBODYSURFACEAREAAMINIMUM0!3)OF0LACEBON OR%."2%,3#MGN ")7FORWEEKS!FTERWEEKSPATIENTSINBOTHARMSN RECEIVED%."2%,MG")7INANOPEN
LABELEXTENSIONPHASE
FORAFURTHERWEEKSTHROUGHWEEK ,/#&ANALYSIS"ASELINE0!3)MEAN PLACEBO%."2%,AND%."2%,%."2%,1-3
§ PASI is a score that combines the amount of psoriatic involvement in each body region (head, arms, trunk and legs) with the measure of severity of psoriatic lesions based on presence of erythema, infiltration and desquamation.2,3
¶ Randomized, double-blind, placebo-controlled study of adult patients with chronic, stable plaque psoriasis involving ≥OFBODYSURFACEAREAANDAMINIMUMPSORIASISAREAANDSEVERITYINDEX0!3) OF%."2%,MGSUBCUTANEOUS3# N ORPLACEBON TWICEWEEKLYFORMONTHSFOLLOWEDBYOPEN
LABEL%."2%,MGTWICEWEEKLY
Percent mean improvement from baseline in DLQI was 70% for ENBREL vs. 6% for placebo.
ENBREL® and Enliven ® are registered trademarks of Immunex Corporation, all used with permission.
© 2010 Wyeth Canada, a Pfizer company, and Amgen Canada. All rights reserved.
References: 1. ENBREL Product Monograph, Amgen Canada Inc. and Wyeth Canada. March 5, 2010. 2. Tyring S, et al. Long-term safety and efficacy of 50 mg of etanercept twice weekly in patients with psoriasis. Arch Dermatol 
3. Data on file, Amgen Canada Inc.

Patient enrolment: call 1.877.9ENBREL (1.877.936.2735) or visit enbrel.ca

21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:09 PM Page 5

THE BEAUTY OF MOVING ON TO LIFE’S POSSIBILITIES †

See prescribing summary on page 21

21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:12 PM Page 6
6 · September 2010
Lead article
Annual report on acne therapy
Acne:
Chronic condition typically
requires several approaches
 Dermatologists
typically find
they need to
employ more
than one therapy
to treat acne in
their patients
he chronic nature of acne
means patients will likely
need to use several thera-
pies to get the condition
under control, Canadian
clinicians inter viewed by T H E
CHRONICLE OF SKIN & ALLERGY agree.
One of the new therapies that is being used to treat
acne is Isolaz.
“It is a neat machine,” says Dr. Ken Alanen, a der-
matologist in Calgary who is an assistant clinical profes-
sor at the University of Calgary and the University of
Alberta in Edmonton. “It works on the deep bumps in
acne, vacuums out the pores, and treats the redness
that is associated with acne.”
Isolaz is a photo-pneumatic therapy that delivers
broadband light to the skin. It has a vacuuming action
that loosens dirt, blackheads, and excess oil that resides
inside pores. Isolaz is a good option for patients with
acne who are pregnant and so cannot utilize any sys-
temic acne treatments, says Dr. Alanen.
Topical tretinoin still mainstay
Patients undergo a series of five treatments with Isolaz,
with treatments spaced out roughly two weeks apart,
adds Dr. Alanen. “Some patients will get a response
after three or four sessions.”
Tretinoin is a mainstay of topical acne therapy, and
Retin-A is one of the tretinoins used to treat acne. One
of the recent advances is the availability of Retin-A
micro, or a micronized formulation of Retin-A, which
comes in two concentrations and which has the advan-
tage of reaching deeper into the skin’s pores beyond the
surface of the skin, explains Dr. Alanen.
Although tretinoins can be irritating to the skin in
some patients, causing flakiness, dryness, and redness,
micronized Retin-A offers efficacy with lesser effects,
according to Dr. Frances Jang, a dermatologist in
THE CHRONICLE of SKIN & A L L E R G Y
Vancouver and a clinical associate professor at the
University of British Columbia in Vancouver.
“[Retin-A Micro] is less irritating than traditional top-
ical tretinoin, and patients are able to better tolerate it,”
says Dr. Jang. “It is also more collagen-enhancing.
Although we take a multi-pronged approach to acne in
most instances, for comedonal acne or for blackheads
or whiteheads, it could be a monotherapy.”
Laser and light therapies have fallen out of favor to
some degree in the treatment of acne because the
patient response has been limited and acne has
recurred, according to Dr. Jang. “I am using intense
pulsed light to treat pigmentary
changes in acne,” she says. “It is not
a primary treatment in my
hands.”Similarly, Dr. Jang uses blue
light in a select group of patients.
Dermatologists have typically
needed to employ more than one
therapy to treat acne in their
patients. The recent approval of a
water-based gel that combines two Dr. Frances Jang
solubilized therapies (tretinoin and
clindamycin phosphate) to treat
acne vulgaris in patients aged 12
years and older by the U.S. FDA,
points to the trend to using combi-
nation treatments. Results from a
clinical trial showed the combina-
tion of tretinoin and clindamycin
phosphate was more effective than
Dr. Martie Gidon
monotherapies such as tretinoin
gel, clindamycin gel, and vehicle
gel.
“We usually combine different medications,’” says
Dr. Jang. “We usually do not use a monotherapy.
Therapies often work synergistically to give more clear-
ing [of acne]. Manufacturers are catching on and realiz-
ing that combining [therapies] is more convenient for
patients.”
Dr. Martie Gidon, a cosmetic dermatologist in
Toronto, director of the Gidon Aesthetics & Medispa,
and a lecturer in the division of dermatology in the fac-
ulty of medicine at the University of Toronto, agrees that
new offerings that combine traditional stand-alone ther-
apies appeal to patients because of expediency.
“It’s about convenience,” says Dr. Gidon, noting
compliance may be improved if the medication regi-
men is more convenient for patients.
Watch for adverse side effects
Some acne therapies include systemic antibiotics like
doxycycline (which is now available in a low dose),
tetracycline, and minocycline. Minocycline can produce
hyperpigmentation, as well as other adverse events, a
fact that clinicians should be informed about, says Dr.
Gidon.
“It’s a good medication, but there are several
Please turn to Acne page 24
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:12 PM Page 7

E W
N

Introducing
Silkis Ointment. ™

Non-steroidal calcitriol.
For the treatment of mild to
moderate plaque-type psoriasis.

r Efficacy (success rate) seen as early as Week 2 (with a statistically significant difference of 7% from vehicle) in two pivotal studies – Success
rates at Week 8 were 37.3% and 36.9% vs. 25.3% and 13.3% in the vehicle group (p=0.009 and p<0.001, respectively)*
r Efficacy did not appear to change over time in one long-term (52-week), uncontrolled, open-label study in 324 subjects†
r Demonstrated safety and tolerability profile – The most common adverse reactions experienced in two 8-week safety studies* and one
long-term (1-year), open-label safety study† were laboratory test abnormality, skin discomfort, pruritus, and psoriasis. In the two pooled 8-week
studies, incidence rates for the most common adverse events were 3.3% vs. 3.6% (vehicle) for laboratory test abnormality, 2.6% vs. 2.1% for skin
discomfort, and 1.4% vs. 1% for pruritus.

Silkis (calcitriol) ointment is a topical non-steroidal antipsoriatic agent indicated for the topical treatment of mild to moderate plaque type psoriasis (psoriasis vulgaris) with up to 35% body surface area involvement. Clinical studies of Silkis
ointment did not include sufficient numbers of subjects 65 years and older to determine whether they respond differently from younger subjects. Silkis is not recommended for pediatric use, as safety and effectiveness in pediatric patients
have not been established.
Slkis ointment is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container; patients with hypercalcemia and those known to suffer from abnormal calcium
metabolism; patients on systemic treatment of calcium homeostasis; and patients with severe renal impairment or end-stage renal disease. Silkis ointment is not for ophthalmic or internal use.
Serum calcium levels should be monitored at regular intervals if risk factors for hypercalcemia are present. If the serum calcium level becomes elevated, calcitriol therapy should be discontinued and the serum calcium level monitored in these
patients until it returns to normal. Due to the potential effect of Vitamin D and its metabolites on calcium metabolism, substances that may increase the absorption of calcitriol must not be added to the ointment or used concomitantly with the
ointment. Silkis ointment must not be covered with an occlusive dressing. Silkis is not recommended for severe, extensive psoriasis (including involvement of more than 35% of the body surface). Silkis should not be applied to the eyes, lips, or
facial skin. Silkis is not indicated for use in other clinical forms of psoriasis. No more than 30 g of Silkis ointment should be used per day.
The most common drug-related adverse reactions that occurred in at least 1% of patients treated with Silkis (n=419) versus calcitriol vehicle ointment (n=420) were: discomfort skin (2.6% vs. 2.1%), pruritus (1.4% vs. 1%), and lab test
abnormality (3.3% vs. 3.6%). Among subjects having laboratory monitoring, hypercalcemia (albumin-adjusted calcium above the upper limit of normal), at any post-baseline point during the 8 week trials, was observed in 24% (18/74) of
subjects in the Silkis group compared to 16% (13/79) of subjects in the vehicle group.
Please see the full Prescribing Information for additional details.
Success = “Clear” or “Minimal” on the global severity score of psoriasis (score of 0 or 1 out of 6)
*Results of two randomized, double-blind, vehicle-controlled studies in adult patients (n=839; Study 1 n=418; Study 2 n=421) with mild to moderate psoriasis. Patients were treated twice daily for 8 weeks with Silkis or vehicle ointment.
†Results of a 1-year, multicentre, open-label, non-comparative safety and efficacy study in patients (n=324) with psoriasis. Silkis was applied twice daily for up to 52 weeks. A total of 239 patients were exposed for 6 months and 116 for at least one year.

Reference: 1. PrSilkis™ Ointment Product Monograph, Galderma Canada Inc., March 9, 2010.

See prescribing summary on page 28

www.galderma.ca
21683B_Skin_Allergy_Pg_:ps 10/18/2010 9:43 PM Page 8

Acne Clearance Treatments with Trios™

Three Month Follow-Up Study
ABSTRACT: The following study evaluates the Trios™ Intense Pulsed Light (IPL) system for the application of Acne clearance. Twenty three patients with
mild to moderate acne, underwent 2 treatments per week for 4 weeks using the Trios™ Acne Clearance applicator with a wavelength of 400-1200nm.
Average fluence of pulses was 5J/cm2 with pulse duration of 25 msec. At 3 months evaluation follow up 83% of the patients experienced significant clearance
(>75%) while 17% demonstrated moderate clearance (50% - 75%) compared to baseline. Overall average clearance of acne lesions was 88.83%. Patients
also showed visible improvement in skin texture, tone and complexion. No adverse effects were reported, except for mild and transient erythema.

Introduction Discussion
Acne Vulgaris is an exceedingly common chronic skin disorder The results of this study confirm that treatment of Acne Vulgaris with the Trios™ IPL system
that affects approximately 70% of adolescents in North America is an effective and safe application. At the conclusion of the study an average improvement
and comprises more than 30% of dermatological visits. The of 88.83% was recorded. Improvement rate was consistent throughout the study for the
disorder is localized to skin regions with a high number of majority of patients (78%). In some cases a withdrawal was recorded, however at the
sebaceous follicles such as the face, back and chest. Acne conclusion of the study, 4 out of 5 of these patients also showed a significant improvement
Vulgaris may lead to long-term scarring and disfigurement, and in their condition. No adverse effects were reported, except for mild and transient erythema.
often contributes to a state of psychological distress, social In addition, all patients demonstrated an improvement in skin texture and quality. The
withdrawal, clinical depression and even suicide. results of this study indicate that treatment with the Trios™ IPL system hinders development
of acne lesions and that results are sustainable over time.
Propionibacterium acne (P. acnes), responsible for the outbreak
of inflammatory acne produce and accumulate endogenous
porphyrins (namely protoporphyrin, uroporphyrin, and
coproporphyrin III) which are the target chromophores for the
acne clearance application. Light-based therapy for acne was
introduced a decade ago and has become an accepted
modality in the armamentarium of acne treatments.
Exposure of inflammatory acne lesions to light utilizing blue,
green and red wavelengths which are absorbed by the
porphyrins induces a photochemical reaction which generates
highly reactive, free radical oxygen that subsequently causes
bacterial destruction. Before After Before After
The IPL acne phototherapy technique thus relies on a
combination of photochemical and photo thermal mechanisms
of action. The wide spectral range of wavelengths optimizes the
trade-off between penetration depth and porphyrins activation
efficiency. Blue light (415-420nm) gives the strongest porphyrin … by
photo activation but poorly penetrates into human skin, whereas
green and red lights, although less effective in photo activation,
have an increased depth of penetration into human skin that
contributes to the stimulation of cytokine that is released from …an advanced phototherapy system for
macrophages and induces an anti inflammatory response.
J AcneClearance
Materials and methods J SkinRejuvenation
23 patients between the ages of 15-29 years, with mild to JLong-Term Hair Removal
moderate facial acne, underwent 2 treatments per week for 4
weeks using the Trios™ acne clearance applicator, which emits
wavelengths from 400 to 1200nm. During the treatment 30-55
pulses of 5j/cm2 at 25 msec. duration were applied, covering
the entire treatment area with no more than 30% overlap. After
the completion of the above treatment schedule, evaluations
were held once a month for 3 consecutive months. Photographs
of the treated areas were taken at baseline, post treatments 2,
4, 6 and 8, and at each of the three monthly evaluation visits.
Lesions were counted using these photographs.
At the same time patients were requested to assess treatment
results and progress using the scale below:
0 - No improvement (<25%)
0.0325 $
1 - Mild improvement (25% - 50%)
the pulse
2 - Moderate improvement (50% - 75%)
3 - Significant improvement (>75%)
Results UNCOMPARABLE RETURN ON INVESTMENT
All patients completed the treatment course and underwent 100 000 PULSES PER TREATMENT HEAD !
monthly evaluation follow up visit for 3 months following the last
treatment. Moreover, all patients reported good response to the J Exceptional results on 83% of patients (acne treatment)
treatment.
J A dramatic improvement in skin texture, tone and complexion in all patients
At the third monthly follow up visit 83% (19/23) of the patients
demonstrated significant clearance (>75%) compared with J Approved by Health Canada
baseline. The rest of the patients, 17% (4/23), demonstrated
moderate clearance (~66%) and underwent 2 additional J A completely pain free treatment
treatments. At the end of the study, an average clearance of
88.83% was recorded for all 23 patients. J A complementary professional training
In 78% (18/23) of the patients, improvement was consistent J An exceptional support for our customer
throughout the study period. Interestingly enough, the patients
assessments correlated with the acne lesion counts: 87% Call 1.877- 585 - 3116
(20/23) assessed the improvement as significant and 13%
(3/23) assessed the improvement as moderate. In all patients a
dramatic improvement in skin texture, tone and complexion was
also visible.
With the exception of transient mild erythema, no adverse
effects were reported and all patients completed the treatment
course and underwent monthly evaluation follow ups for 3
months following the last treatment. Moreover, all patients
reported good response to the treatment. www.danielehenkel.com or www.vioramed.ca
21683B_Skin_Allergy_Pg_:ps 10/20/2010
THE CHRONICLE of S K I N & A L L E R G Y
Psoriasis
Anxiety, depression common in psoriasis
 New study provides additional evidence that psoriasis affects the mental health of patients
D
ata suggests that pso-
riasis patients appear
to have an increased
risk of depression, anxiety,
and suicidal actions, accord-
ing to a study published in the
August issue of Archives of
Dermatology (2010; 146[8]:
891-895).
“Over the years, studies
have evaluated mental health
in small samples of patients
with psoriasis using question-
naires which are used for
research
purposes.
Our goal
was to
evaluate a
b r o a d
popula-
tion of
psoriasis
patients
Dr. Joel Gelfand
to deter-
mine if
they were
more like-
ly to be
d i a g -
n o s e d
clinically
w i t h
Steve Joordens, PhD d e p r e s -
sion and
anxiety and be more likely to
attempt to complete sui-
cide,” said Dr. Joel Gelfand,
assistant professor of derma-
tology and epidemiology
University of Pennsylvania.
Retrospective analysis
“Although dermatologists
who care for patients with
psoriasis know the burden
this disease creates, it is
important to have objective
data evaluating the risk of
serious mental health out-
comes in the patients,” indi-
cated Dr. Gelfand, the senior
author of the study.
During this study, investi-
gators from the University of
Pennsylvania examined data
obtained from electronic
medical records in the
United Kingdom from 1987
to 2002. The analyses includ-
ed 146,042 patients with
mild psoriasis, 3,956 patients
with severe psoriasis, and
766,950 patients without
psoriasis.
The researchers indicat-
ed that five control patients
for each patient with psoria-
sis were selected from the
10:13 PM Page 9
6 September 2010 · 9
same practice and similar psoriasis, 25.9 per 1,000 indi- and 0.4 per 1,000 per year for sis had elevated hazard ratio
entry dates. Patients were viduals per year were diag- suicidality, the study authors of outcomes compared with
defined as having new-onset nosed with depression, 20.9 reported. older patients who had psori-
depression, anxiety, or suici- per 1,000 per year with anxi- Researchers also indicat- asis.
dality if corresponding diag- ety, and 0.9 per 1,000 per ed in their report that the haz- “This research highlights
nostic codes appeared in year with suicidality. The ard ratio of depression was the importance of us not
their records after follow-up overall rate of these cases higher among severe psoria- downplaying the feelings of
began. attributable to psoriasis was sis patients compared with pre-teens and teens that have
11.8 per 1,000 individuals per patients who had mild psoria- psoriasis, acne, or other skin
Retrospective analysis
Findings reveal that of year for depression, 8.1 per sis. Overall, data reveal that
1,000 per year for anxiety, younger patients with psoria- Please turn to Psoriasis page 29
patients with mild or severe
Dovobet® (calcipotriol betametha-
sone dipropionate) ointment is
indicated for the topical treat-
ment of psoriasis vulgaris for up to
4 weeks.
Help your patients
Application on large areas of damaged
skin, in skin folds, or under occlusive
dressings should be avoided due to
increased systemic absorption of
treat their psoriasis
corticosteroids. Dovobet® (calcipotriol
betamethasone dipropionate) should not
be used on the face or in children.
If long-term therapy is anticipated, it
is recommended that treatment be
interrupted periodically or that one
area of the body be treated at a time.
Prolonged use of corticosteroid-containing
preparations may produce striae or atrophy
of the skin or subcutaneous tissues.
There may be a risk of rebound psoriasis
when discontinuing corticosteroids after
prolonged periods of use. Hypercalcemia
can develop but is usually associated
with excessive administration (maximum
recommended weekly amount of 100 g).
If serum calcium levels become elevated,
Dovobet® should be discontinued and
serum calcium levels measured once
weekly until they return to normal.
The most common adverse reaction
associated with Dovobet® (calcipotriol/
betamethasone dipropionate) was
pruritus. Calcipotriol is associated
with local reactions such as transient
lesional and perilesional irritation. Topical
corticosteroids can cause the same
spectrum of adverse effects associated
with systemic steroid administration,
including adrenal suppression.
Adverse effects associated with
topical corticosteroids are generally
local and include dryness, itching,
burning, local irritation, striae, atrophy
of the skin or subcutaneous tissues,
telangiectasia, hypertrichosis, folliculitis,
skin hypopigmentation, allergic contact
dermatitis, maceration of the skin, miliaria,
or secondary infection. If applied to the
face, acne rosacea or perioral dermatitis
can occur. In addition, there are reports
of the development of pustular psoriasis
from chronic plaque psoriasis following
reduction or discontinuation of potent
topical corticosteroid products.
Due to the corticosteroid component,
Dovobet® is contraindicated for the
treatment of viral, fungal, or bacterial
skin infections; tuberculosis of the skin; NOW ON PROVINCIAL
syphilitic skin infections; chicken pox; FORMULARY IN AB, SK,
eruptions following vaccinations; and in
viral diseases such as herpes simplex,
Once Daily. Effective psoriasis therapy. ON AND QC*
varicella, and vaccinia. Available in 60 g and 120 g tubes.
Calcipotriol when used in combination with
ultraviolet radiation (UVR) may enhance For the product monograph or for
the known skin carcinogenic effect of UVR. further information, please contact
Medical Information at LEO Pharma Inc. ®
Not for ophthalmic use.
1-800-263-4218.
* Exception medication
® Registered trademarkof LEO Pharma A/S used
under license by LEO Pharma Inc.
Thornhill, ON www.leo-pharma.com/canada
See prescribing summary on page 27
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:13 PM Page 10

10 · September 2010
s THE CHRONICLE of S K I N & A L L E R G Y

Eczema: Evidence indicates dogs confer allergen tolerance

three years. a dogless home developed the condi- confidence interval from 3.1 to 57.9.
based on either parental report Of the 636 children who complet- tion, with an adjusted odds ratio of The researchers found their study
through a questionnaire—which ed the study, 184 had a dog in the 3.9 at a 95% confidence interval from matched previous data that showed
included scratching and redness, home before age one, while 121 had 1.6 to 9.2. dog ownership provided a significant,
raised bumps, or dry skin and scaling a cat. However, only 14% of children four-fold protective effect against
as markers—or diagnosis through a A child’s positive test for dog with dogs who tested positive for dog eczema at four years when compared
healthcare professional associated allergy on an SPT was associated allergy on an SPT were diagnosed with households without dogs. They
with the study, which included ery- with an increased risk of eczema in with eczema, while 9% of those who also noted children of cat owners
thema, papulation, excoriations, or dogless homes when compared tested negative had the condition with were 13 times more likely to develop
lichenification as signs of the condi- against eczema risk for kids with an adjusted odds ratio of 1.3 at a 95% the skin condition than children of
tion. dogs. confidence interval from 0.3 to 6.8. households without cats.
The control group included Of those from homes without Dog ownership may help allergens The researchers also found that
infants who Among kids without cats, kids in a home with a dog were pro-

T
neither had 33% of those with a cat tected from positive SPT results for cat
eczema by allergy, suggesting dog ownership
way of
he researchers found their study matched allergy developed
may develop childhood tolerance to a
eczema, compared with
parental previous data that showed dog ownership 13% of those without a variety of allergens. They attributed
report nor this to patients with dog allergies
were report-
provided a significant, four-fold protective cat allergy with an adjust- developing high levels of interleukin-
ed odds ratio of 1.1 at a
ed to have effect against eczema at four years when 95% confidence interval 10 and interferon-gamma after
the condi- from 0.5 to 2.7, a non- becoming tolerant.
tion after compared with households without dogs. significant difference. The team was unable to identify
physical Children of cat own- factors exacerbating eczema in cat-
examination ers fared worse, as 54% allergic children.
by a health- of children who tested Researchers reported no conflicts
care professional. dogs who tested positive for dog aller- positive for cat allergy developed of interest.
A child was considered positive gy on an SPT, 30% developed eczema, while only 11% of those who Copyright MedPage Today, LLC. All
for an allergen if he or she tested pos- eczema, while only 15% of children tested negative also had eczema with rights reserved. Reprinted with per-
itive at least once from age one to who tested negative for the allergy in an adjusted odds ratio of 13.3 at a 95% mission. www.medpagetoday.com

ECZEMA FLARES ARE ALWAYS WAITING TO ATTACK.

THAT’S WHY WE ARE EXPLORING NEW WAYS TO HELP

MANAGE THE CHRONIC COURSE OF RECURRING FLARES.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:35 PM Page 11

THE CHRONICLE of S K I N & A L L E R G Y

Skin infection research September 2010 · 11

Chronic wounds Unusual fungal infections

Vaccine in pyoderma Septic arthritis reported

 Appears to boost effects of basic therapy  Arthritis linked to M. indicus; skin infection also

Data reveal that the inclusion of the bacterial polycomponent vaccine
Immunovac in the complex treatment of patients with chronic pyoderma
promotes enhancement of the therapeutic effect of other basic therapy
and corrects immunologic parameters (Zh Mikrobiol Epidermiol
Immunobiol 2010; (4):31-37).
During this study, 95 patients with different clinical forms of chronic
pyoderma (furunculosis, hydradenitis, chronic ulcerative and ulcerative-
vegetans pyoderma, folliculitis, impetigo, etc.) were studied. In all, 59
patients received immunotherapy with Immunovac vaccine together with
basic therapy; 36 patients made up a control group treated only with basic
therapy. Findings show that the use of Immunovac vaccine enhanced the
clinical effect of basic therapy, expressed as a decrease of severity and
frequency of disease relapses irrespective of clinical form and severity of
pyoderma. Overall, the therapeutic effect during use of Immunovac vac-
cine amounted to 84.7% after 12 months of follow-up, and 41.6% in the
control group. An increase in the functional activity of neutrophils, sub-
population of lymphocytes with markers CD4+, CD8+, CD72+, affinity of
antibodies as well as induced production of IFNalpha and IFNgamma was
also noted.
Results show that trimethoprim-sulfamethoxazole, rifampin, fusidic acid,
and mupirocin appear to be more suitable for treatment and decoloniza-
tion of staphylococcus aureus in pediatric patients with atopic dermatitis
(AD), investigators reported in the Aug. 12, 2010 issue of Pediatric
International.
During the study, nasal swabs from 168 children with AD and 20 chil-
dren with AD plus concurrent skin and soft-tissue infections (SSTI) were
collected between 2005 and 2008. Data reveal that 78 (46.4%) healthy chil-
dren with AD were colonized with S. aureus, and 24 (30.8%) had methi-
cillin-resistant S. aureus (MRSA). Among the 20 SSTI infecting strains, 12
(60%) were MRSA. Antimicrobial susceptibility testing showed that, after
penicillin, colonizing and SSTI infecting strains had the highest rates of
resistance to erythromycin (50% and 70%, respectively). All isolated strains
were susceptible to vancomycin, rifampin, and mupirocin. Multi-drug resis-
tance was found in 70% of the colonizing and 50% of the SSTI infecting
strains. D-test assay revealed inducible clindamycin resistance in 75% of
the colonizing strains. The most prevalent resistance gene was ermB
which was present in 94.9% and 92.9% of colonizing and SSTI infecting
strains, respectively, the researchers said.

Skin infection update

LESS SURGICAL INFECTION SEEN
WHEN APS CLOSURE EMPLOYED
Data show that a skin-approximating
closure with a subcuticular purse-
string of the stoma site leads to less
surgical site infection than a primary
closure (PC), investigators reported
in the Aug. 12, 2010 online issue of
the World Journal of Surgery. This
investigation involved researchers
retrospectively assessing consecu-
tive patients undergoing stoma clo-
sure between 2002 and 2007 by two
surgeons at a single tertiary-care
institution. In all, there were 61
patients in the PC group (surgeon A:
58 of 61) and 17 in the skin-approxi-
mating, subcuticular purse-string
closure (APS) group (surgeon B: 16
of 17). The two groups were similar
in baseline and intraoperative char-
acteristics, except that patients in
the PC group were more often diag-
nosed with benign disease
(p=0.0156) and more often had a
stapled anastomosis (p=0.002). The
overall SSI rate was 14 of 78 (18%).
All surgical site infections occurred
in the PC group (14 of 61 vs. 0 of 17,
p=0.03).
PRESENCE OF S AUREUS NOT
SIGNIFICANT IN EASI SCORE
Study results suggest that the expres-
sion of a superantigen by S aureus
alone does not play an important
role in the increased skin inflamma-
tion associated with staphylococcal
infection in childhood atopic der-
matitis (AD), investigators reported
in the Aug. 2, 2010 issue of the
British Journal of Dermatology. A
total of 52 children with clinically
impetiginized lesions of AD which
were positive for S aureus were
enrolled in this study. Each lesion
was graded clinically using the
Eczema Area and Severity Index
(EASI), and then fluid was obtained
from the lesion for quantitative bac-
terial culture and measurement of
bacterial products lipoteichoic acid
(LTA) and staphylococcal protein A
(SPA) and cytokines.
Findings show that 54% (28 of
52) of the staphylococcal isolates
encoded a superantigen, but the
presence of a superantigen had no
significant effect on EASI score,
amounts of bacterial products, or
inflammatory cytokines in the AD
lesion.
NAIL AVULSION: STERILE SALINE
SOLUTION REDUCES POTENTIAL
BACTERIAL LOAD
Findings show that the incorporation
of intraoperative irrigation of sterile
saline solution after nail avulsion
surgery reduces potential bacterial
load (Dermatol Surg Aug. 2010;
36(8):1258-1265). The overall aim of
this investigation was to compare
the antiseptic efficacy of two skin
pretreatment methods before toe-
nail avulsion surgery. Two presurgi-
cal methods were performed on 24
patients each (48 patients total).
Swab samples were taken from
each patient at five distinct stages
(pretreatment, post-treatment, after
surgery, after saline solution irriga-
tion of the nail bed, and after phenol
application) throughout the surgical
procedure, and bacterial culture
analysis was performed. Both meth-
ods were effective at reducing the
initial bacterial load when used at
pretreatment, but the reduction in
bacterial load was lost after the
surgery. An interoperative irrigation
step was effective in reducing the
bacterial load by 95.2% and 95.3%,
respectively.
LESION FORMATION AFTER
DRAINAGE OF ABSCESSES MAY BE
DECREASED BY TRIMETHOPRIM-
SULFAMETHOXAZOLE
Investigators suggest that after the
incision and drainage of uncompli-
cated abscesses in adults, treatment
with trimethoprim-sulfamethoxazole
does not reduce treatment failure
but may decrease the formation of
subsequent lesions (Ann Emerg Med
Sept 2010; 56(3):283-287).
This multicenter, double-blind,
randomized, placebo-controlled trial
involved 212 patients randomized to
either oral trimethoprim-sul-
famethoxazole or placebo after
uncomplicated abscess incision and
drainage. Findings show that
researchers observed a statistically
similar incidence of treatment failure
in patients receiving trimethoprim-
sulfamethoxazole (15/88; 17%) ver-
sus placebo (27/102; 26%). On 30-
day follow-up (successful in 69% of
patients), the researchers observed
fewer new lesions in the antibiotic
(4/46; 9%) versus placebo (14/50;
28%) groups, difference 19%, 95%
confidence interval 4% to 34%,
p=0.02.

IND
INDICATIONS: The treatment of primary and secondary For complete warnings/precautions, adverse events,
skin infections caused by sensitive strains of S. aureus, dosing and patient selection information see the
Streptococcus species and C. minutissimum. Primary skin
Stre Product monograph which is available upon request.
infections
infe that may be expected to respond to treatment with For further information, please contact Medical Information
fusidic
fusi acid topical include: impetigo contagiosa, erythrasma at LEO Pharma Inc. 1-800-263-4218.
and secondary skin infections such as infected wounds.
PRECAUTIONS:
PRE Fusidic acid topical preparations should
not be used in or near the eye because of possibility of
conjunctival
con irritation.
Fusidic acid /
® Registered trademark of LEO Pharma A/S used sodium fusidate
under licence by LEO Pharma Inc. Thornhill ON
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:05 PM Page 12

12 · September 2010
CDF news THE CHRONICLE of S K I N & A L L E R G Y

C a n a d i a n D e r m a t o l o g y Fo u n d a t i o n

Annual CDR Research Grants announced

 Total of $475,000 awarded to Canadian investigators to advance research into skin disease

T he Canadian Dermatology Foundation awarded a total of $475,000 in

research grants to 18 investigators at the annual CDF Research Grant
Awards Reception, held during the annual scientific sessions of the
Canadian Dermatology Association in St. John’s, Nfld.
CDF President Dr. Neil H. Shear congratulated the researchers, and
expressed sincere thanks to the corporate benefactors and CDF members for
their financial support, which makes the annual grants possible.
Dr. Shear noted that, “A record number of new Benefactor Life Members
and Life Members have joined our growing CDF community. I am honored to
be president of this dynamic group of people, dedicated to keeping the dream
growing for young, high-level investigators. We all benefit from Canadian
research”.
The Canadian Dermatology Foundation was established in 1969 to provide
assistance with research into skin disease. The CDF is the leading source of
funding for peer-reviewed dermatological research in Canada, with grants to
date totalling over $5 million. Advances in the study and knowledge of skin
disease generate improved methods of diagnosis and treatment, to the benefit
of Canadian dermatologists and their patients.
For more information, please visit www.cdf.ca
Grant recipients Dr. George S. Williamson Research Grant 2010 CDF Research Grants: (l-r) Dr. Neil Shear, CDF President, Dr. Wayne Gulliver,
(CDF) $10,000 recipient of the CDF-Dr. George S. Williamson Research Grant, and Dr. Gilles Lauzon,
Dr. Akerke Baibergenova
Heritability of familial psoriasis in
CDF Secretary.
University of Toronto, Toronto
Newfoundland and Labrador
CDF Research Grant $5,000
Hospital admissions for cellulitis across Canada
Dr. Peter Robin Hull
University of Saskatchewan, Saskatoon
Dr. Katie Beleznay
Winefride M. P. Raye Research Grant (CDF)
University of British Columbia, Vancouver
$10,000
CDF—La Roche-Posay Research Grant $10,000
Genetics and acne: a Canadian genome wide
Genomic expression profile (GEP) of erythema-
association replication study forming part of a
totelangiectatic rosacea
collaborative international study

Dr. Jan Dutz

Dr. Habib Kurwa
University of British Columbia, Vancouver
University of Calgary, Calgary
CDF Research Grant $20,000
CDF-TaroPharma Research Grant $15,000
Topical immunomodulation for the desensitiza-
Polyomavirus in non-melanoma skin cancer
tion to contact sensitizers

Dr. Richard G.B. Langley

Dr. Mehran Ghoreishi
QEII Health Sciences Centre, CDHA, Halifax
University of British Columbia, Vancouver
CDF-Stiefel, a GSK company Research Grant
CDF Colin Ramsay Endowment Fund Research
$25,000
Grant $10,000
Confocal scanning laser microscopy of benign
Evaluation of type 1 interferon expression in
and malignant facial papules
skin lesions of morphea 2010 CDF Research Grants: (l-r) Dr. Kenneth Kobayashi, CDF Treasurer, Dr. Peter Hull,
Dr. Tim Lee
recipient of CDF-Winefride M.P. Raye Research Grant, and Dr. Neil Shear, CDF President.
Dr. Wayne P. Gulliver
University of British Columbia, Vancouver
Memorial University of Newfoundland,
CDF-Dermik/Sanofi-Aventis Research Grant
St. John’s, Newfoundland
$25,000

CDF Benefactor Life Members’

Research Grant $5,000
Methodology development and
assessment for tracking pig-
mented skin lesions with stan-
dard and stereoscopic photogr-
phy

Dr. Gang Li
BC Cancer Agency, Vancouver
CDF-Amgen Canada/Wyeth
Pharmaceuticals Research
Grant $25,000
Mechanisms of integrin-linked
kinase mediated angiogenesis
in melanoma

Dr. Kevin McElwee

University of British Columbia,
Vancouver
CDF-Neutrogena Research
Grant $25,000
Regulation of hair cycle by avb6
integrin-mediated activation of
TGF-b1
Dr. P. Régine Mydlarski
CDF Board Members at the Research Grant Awards.
University of Calgary, Calgary
CDF-LEO Dermatology Research Grant $50,000
CDF-Astellas Pharma Canada Research Grant
$25,000
The role of microRNAs in cutaneous squamous
cell carcinomas
Dr. Elena Pope
The Hospital for Sick Children, Toronto
CDF-TaroPharma Research Grant $10,000
Vitamin D in patients with atopic dermatitis and
psoriasis: a randomized, double-blinded,
placebo-controlled study
Please turn to CDF awards page 25
21683B_Skin_Allergy_Pg_:ps 10/22/2010 12:19 PM Page 13

S p e c i a l r e p o r t on A K s
from the CDA Annual Meeting in St. John’s, NL

New approach to treatment of actinic keratoses outlined

Field therapy with imiquimod 3.75% useful for
treating subclinical as well as clinical AK lesions
new therapeutic approach to the such as the face, balding scalp, nose,

A
treatment of actinic keratoses
(AKs) may provide physicians
with an important option in deal-
ing with these pre-cancerous
lesions. That’s according to Dr. Darrell
Rigel, who addressed attendees at a satel-
lite symposium during the 85th annual
conference of the Canadian Dermatology
Association in St. John’s, Newfoundland
and Labrador.
“There is a histologic and molecular
continuum [between AKs and basal cell
carcinoma and squamous cell carcinoma
(BCC/SCC)],” Dr. Rigel, Clinical Prof-
essor, New York
University Medical
Center, said. “Therefore,
early treatment of AKs is
warranted.”
The approval earlier
this year of imiquimod
3.75% (Zyclara, Graceway Dr. Rigel
Canada Company), used
as a field therapy, means that physicians
can treat both clinical and subclinical AK
lesions before the lesions might progress to
some form of skin cancer.
AKs in clinical practice
There is a convincing clinical rationale
that this new actinic keratoses treatment
approach and its integration into practice
will provide significant benefit to both
patients and healthcare systems around
the world, said Dr. Rigel.
“We should look at actinic keratoses
as the tip of the iceberg.”
It has become increasingly under-
stood at a clinical level that all AKs
should be treated—the risk of AKs pro-
gressing to invasive SCC is estimated to
range from 0.025% to 16% per year. Dr.
Rigel noted that during 1990 to 1994,
AKs were the 3rd most common reason
for patients to seek an appointment with
a dermatologist, representing 11.5% of
visits, and during the period 1990 to
1999, AKs were the 2nd most common
reason, representing 14% of visits.
AKs remain a controversial topic,
Dr. Rigel said, but it is generally agreed
they are precursors to the development
of skin cancer. The small scaly lesions
most often appear on sun-exposed areas
AKs in the Canadian landscape
The chair of the session, Dr. Marc Bourcier of Moncton, N.B., outlined two recent
Canadian surveys that indicate neither GPs nor patients seem to have a very good
grasp of how to identify AK lesions (The Chronicle of Skin & Allergy 2010;
16:2(Mar), page 1).
In a consumer poll conducted in 2009, eight out of 10 patients were unable to
recognize an AK lesion. In a 2010 poll that involved 200 GPs and 46 dermatolo-
gists, 42% of respondents noted that they find it difficult to identify an AK lesion,
and 80% of GPs indicated they would like more information on how to identify an
AK lesion.
Dr. Bourcier noted that with the aging population, there is a higher probabili-
ty that people are more likely to develop actinic keratoses and/or basal cell carci-
noma or squamous cell carcinoma.
neck, and tips of the ears. The pathobi-
ology of AKs is fairly well understood,
and it is clear the lesions are induced by
exposure to UV light. Dr. Rigel noted
that UV light is a complete carcinogen
that affects all three stages of carcino-
genesis: initiation, promotion, and pro-
gression.
Pharmacoeconomics of AK treatment
Clinical issues aside, all countries are
concerned about the healthcare costs of
actinic keratoses, Dr. Rigel said, noting
the expenses related to AKs are much
higher than many might
expect.
In 2004, he said, the
economic impact of AKs
in the United States was
determined to be US$867
million, and when direct
and indirect costs were
Dr. Bourcier
added in, the price tag rose
to US$1 billion. Including
intangibles such as lost wages, etc. hiked
the ultimate cost to US$2.4 billion.
Studies have shown that patients with
more AKs are at greater risk of develop-
ing SCC, he said, because they share not
only markers but precursors such as
exposure to UV light as well. “AKs and
SCCs share many of the same molecular
changes,” Dr. Rigel said. “They are histo-
logically similar, and we see many of the
same features.”
Researchers have estimated that 60%
of SCCs arise from AKs.
“The other questions that are equally
important [when considering treatment of
these lesions],” Dr. Rigel said, “is that the
issue is not the patient with one AK, but
the one patient with multiple AKs.
“The other issue is which AK will
progress, and the answer to that question
is that we just don’t know. We have no
way of actively determining which AK is
the one that will develop into squamous
cell carcinoma.” Dr. Rigel noted that, on
average, 6 to 10% of actinic keratoses
would develop into squamous cell carci-
noma over 10 years.
Dr. Rigel cited a study by Robin
Marks, et al (Br J Dermatol 2006;
155:23-26) which determined the inci-
Direct and indirect costs of AKs to the Nor th
American economy are estimated at US$1 billion
dence of a single AK developing into dose/response relationship, and to simpli-
SCC over a span of one year is approxi- fy treatment and shorten duration and fre-
mately 1/400. The evidence also indicated quency, Dr. Rigel reported.
that patients with multiple lesions might Dr. Rigel described a study by
develop SCC at the rate of 6.1 to 10%. Swanson, et al (J Am Acad Derm 2010;
62(4):582-590) that evaluated field ther-
Development of field therapy
apy using imiquimod 2.5% and 3.75%
Field therapy is an approach to AK treat- for short-course treatment of the full
ment that permits physicians to treat not
face or balding scalp over two two-week
only those lesions that are visible clini- treatment periods separated by a two-
cally, but also subclinical lesions.
week no-treatment interval. Efficacy
Dr. Rigel outlined a study by was assessed at eight weeks post-treat-
Kravtchenko, et al (Br J Dermatol 2007;
ment. Primary outcome assessment was
157 (Suppl 2):34-40) that looked at field
100% clearance, and the secondary out-
therapy vs. targeted therapy for AKs, come was clearance greater than or
and also assessed combination therapy
equal to 75%.
for AKs (imiquimod, 5FU, and cryother- In the study, a total of 479 patients
apy).
were randomized to placebo, or imiqui-
In the study, histologically confirmed mod 2.5% or imiquimod 3.75%. Complete
AKs were treated with imiquimod 5%
and partial clearance (greater than or
(26 patients, treated three times/week for equal to 75% lesion reduction) rates were
four weeks, followed by a four week rest 6.3% and 22.6% for placebo, 30.6% and
period, then a second cycle of three 48.1% for imiquimod 2.5%, and 35.6%
times/week for four weeks); 5-FU (24 and 59.4% for imiquimod 3.75%, respec-
patients, b.i.d. for four weeks); cryother- tively. Median reductions from baseline in
apy with liquid nitrogen (25 patients, 20 lesion counts were 25.0% for placebo,
to 40 seconds for each lesion for up to 71.8% for imiquimod 2.5%, and 81.8%
two treatments). for imiquimod 3.75%.
At 3 months, the test of cure was
“Consistently, 3.75 is better than 2.5,”
similar between imiquimod 5% and 5-
Dr. Rigel said.
FU, but imiquimod showed greater sus-
Dr. Rigel briefly outlined a study
tained clearance rates at 12 months (73%
that compared imiquimod plus
vs. 33%). For cryotherapy, sustained
cryosurgery as field therapy for AKs
clearance at 12 months was 4%. versus cryotherapy plus placebo.
Imiquimod also showed more favorable
Baseline was considered to be greater
cosmetic outcome at 12 months (81% vs. than or equal to 10 AKs on the face, he
4% for both 5-FU and cryotherapy).
said. The results of the study indicated
that imiquimod plus cryotherapy pro-
New ways to treat AKs
vides good sustained clearance, and that
The objectives of the new generation of the imiquimod significantly adds to
topical treatments for AK should be to cryosurgery alone. Cryotherapy is effec-
expand the treatment area, shorten the tive, but cryotherapy and imiquimod
dosing regimen by increasing the together provide even better results.
Supplement to The Chronicle of Skin & Allergy, September 2010. Chronicle is an independent medical
news service that provides educational updates regarding medical developments around the world.
Views expressed are those of the participants and do not necessarily reflect those of the publisher or
sponsor.
Support for distribution of this report was provided by Graceway Canada Company through an
educational grant without conditions. Information provided in this report is not intended to serve as the
sole basis for individual care.
Printed in Canada for Chronicle Information Resources Ltd., 555 Burnhamthorpe Rd., Suite 306,
Toronto, Ont. M9C 2Y3. Telephone 416.916.2476; facsimile 416.352.6199; e-mail:
health@chronicle.org. Copyright 2010 by Chronicle Information Resources Ltd., except where noted.
All rights reserved. Reproduction in any form is expressly prohibited without written permission of the
publisher.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:09 PM Page 14

14 · September 2010 THE CHRONICLE of S K I N & A L L E R G Y

Acne research
Acne scars Acne studies

Laser improves scars Lower triacylglycerols

 Minimum of adverse effects seen in small study  Acne improved in lactoferrin study group

Data show that the nonablative 1,540-nm fractional laser improves acne
scars with a minimum of adverse effects (Lasers Med Sci Sept 2010;
25(5):749-754). The efficacy and adverse effects of 1,540-nm nonablative
fractional laser treatment of acne scars were analysed in 10 patients with
acne scars were included. Two intraindividual areas of similar size and
appearance within contralateral anatomical regions were randomized to
(1) three monthly laser treatments with a StarLux 1,540-nm fractional
handpiece, and (2) no treatment. Blinded on-site clinical evaluations were
performed before treatment, and at four and 12 weeks post-treatment.
End-points were overall change in scar texture (from score 0, even tex-
ture, to 10, worst possible scarring), adverse effects, change in skin colour
(from score 0, absent, to 10, worst possible), and patient satisfaction (from
score 0, no satisfaction, to 10, best imaginable satisfaction).
Findings show that after treatment, laser-treated scars appeared more
even and smooth than untreated control areas. Patients were satisfied
with the treatment and five of the 10 patients evaluated their acne scars as
moderately or significantly improved. No differences were found in skin
redness or pigmentation before and after treatment. Patients experienced
moderate pain, erythema, edema, bullae, and crusts.
Results suggest that lactoferrin-enriched fermented milk ameliorates
acne vulgaris with a selective decrease of triacylglycerols in skin surface
lipids (Nutrition Sept 2010; 26(9):902-909).
During this 12-week, double-blind, placebo-controlled study patients
between 18 and 30 years of age were randomly assigned to ingest fer-
mented milk with 200 mg of lactoferrin daily (n=18, lactoferrin group) or
fermented milk only (n=18, placebo group). The study data indicated that
acne showed improvement in the lactoferrin group by significant decreas-
ing the inflammatory lesion count by 38.6%, total lesion count by 23.1%,
and acne grade by 20.3% compared to the placebo group at 12 weeks.
Furthermore, sebum content in the lactoferrin group decreased by 31.1%.
Overall, the amount of total skin surface lipids decreased in both
groups. However, of the major lipids, the amounts of triacylglycerols and
free fatty acids decreased in the lactoferrin group, whereas the amount of
free fatty acids decreased only in the placebo group. The decreased
amount of triacylglycerols in the lactoferrin group was significantly corre-
lated with decreases in serum content, acne lesion counts, and acne
grade. The authors concluded that no alterations in skin hydration or pH
were noted in either group.

ISOTRETINOIN USE COULD
INCREASE RISK OF CV DISORDERS
Researchers caution in the Aug. 2010
issue of Clinical Experimental
Dermatology that isotretinoin may
increase the risk of cardiovascular
disorders by causing hyperhomocys-
teinemia (35(6):624-626).
The overall aim of this study was
to evaluate homocysteine levels and
the vitamins responsible for its
metabolism in patients with moder-
ate to severe acne vulgaris on
isotretinoin therapy, before and after
treatment. The authors noted that
they found increased level of homo-
cysteine in patients after two months
of taking isotretinoin.
They concluded that the respon-
sible enzyme for homocysteine
metabolism, cystathionine-beta-syn-
thase, might also be affected by
isotretinoin-induced liver dysfunc-
tion, which leads to hyperhomocys-
teinemia, an independent risk factor
for thrombovascular diseases.
Acne update
SUBDERMAL MINIMAL SURGICAL
TECHNIQUES IMPROVE SCARS
Data published in the June 2010
issue of Dermatology Surgery sug-
gest that subdermal minimal surgery
technology is an effective and safe
method for improving acne scars.
A total of 10 Korean patients
(Fitzpatrick skin type II-V) with acne
scars were enrolled. Each partici-
pant received three sessions of sub-
dermal minimal surgery technology
at four-week intervals. The treatment
parameters were a 0.15-mL volume
of hyaluronic acid (HA) and 70%
pressure power with a 10- x 10-mm
square-shaped tip. Findings indicate
that all volunteers completed the
three treatment sessions and were
satisfied with the procedure. Three
months after the last treatment ses-
sion, two patients had improvement
of greater than 75% in acne scars, six
had 50% to 75% improvement, and
two had 25% to 50% improvement.
The patients’ degree of satisfaction
was similar to the physicians’ assess-
ment. There were no side effects
except transient spot bleeding at
entry points and slight edema that
resolved within 48 hours.
ATROPHIC ACNE SCARS RESPOND
TO RESURFACING DEVICE
Carbon-dioxide ablative fractional
resurfacing device appears to be an
effective and well tolerated for the
treatment of atrophic acne scars
among patients of Asian decent (J
Am Acad Dermatol Aug. 2010;
63(2):274-83).
Over the course of this study, 13
patients including eight females and
five males aged 25 to 52 years with
skin phototype IV and atrophic acne
scars were treated with three ses-
sions of carbon-dioxide ablative frac-
tional resurfacing laser on an average
of seven week interval. Six months of
follow-up indicate 85% of the sub-
jects were rated as having at least
25% to 50% improvement of scars.
Improvement significantly pro-
gressed from the one month follow-
up to the six month follow-up
(p=0.002). At one month after three
treatments, surface smoothness
(p=0.03) and scar volume (p<0.001)
significantly improved, compared to
baseline measurements. Of the sub-
jects, 62% rated themselves with at
least 50% improvement in their
scars.
TETRACYCLINE, DOXYCYCLINE
ASSOCIATED WITH IBD?
New findings caution that tetracy-
cline class antibiotics—particularly
doxycycline—may be associated
with the development of inflamma-
tory bowel disease (IBD) and
Crohn’s disease (CD) (Am J
Gastroenterol Aug. 2010).
Investigators performed a retro-
spective cohort study using The
Health Improvement Network data-
base of the United Kingdom. They
identified 94,487 individuals with
acne who were followed up by a
general practitioner for 406,294 per-
son-years. A prescription for minocy-
cline was received by 24,085 individ-
uals, for tetracycline/oxytetracycline,
38,603 individuals, and doxycycline,
15,032 individuals.
Overall, IBD was noted in 41
individuals exposed to minocycline,
79 exposed to tetracy-
cline/oxytetracycline, 32 exposed to
doxycycline, and 55 (0.11%) not
exposed to any of these antibiotics.
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:15 PM Page 15

* results may not be typical of the general population.

MetroGel 1%: ®

powerful rosacea fighter

Especially effective against the inflammatory, papulopustular
symptoms of rosacea1
MetroGel 1% (metronidazole topical gel, 1%) is indicated for the treatment of inflammatory papules,
pustules and erythema of rosacea. MetroGel 1% is contraindicated in individuals with a history of
hypersensitivity to metronidazole or other ingredients of the formulation. MetroGel 1% should be
used with care in patients with evidence of, or history of; blood abnormalities, individuals who are
pregnant or nursing, and in individuals who are exposed to excessive sunlight, including sunlamps
and tanning beds. Avoid contact with the eyes.
Physicians should consider the most appropriate formulation (gel, cream or lotion) for their patients.
Significant therapeutic results should be noticed within three weeks. Clinical studies have demonstrated
continuing improvement through nine weeks of therapy. Although rosacea is a chronic disease, data on
the long-term use of MetroGel 1% is not available. In controlled clinical trials, patients were treated up to
10 weeks. The dosage required for long-term administration is uncertain. Drugs that may interact with
MetroGel 1% include coumarin, warfarin, other imidazole preparations such as clotrimazole and
tioconazole, and possibly alcohol.
Adverse reactions attributed to MetroGel 1% were reported at a frequency of <1%. Reactions
included dry skin, erythema, pruritus, skin burning sensation, skin irritation, rash papular, skin
desquamation, skin tightness, facial oedema, urticaria, conjunctivitis, eye irritation and dyspepsia.
The majority of adverse reactions were mild or moderate in severity.
Reference: 1. MetroGel® 1% Product Monograph. Galderma Canada Inc., 2007.

Prescribe
The Power of one
metronidazole topical gel

See prescribing summary on page 24

21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:15 PM Page 16

THE CHRONICLE of S K I N & A L L E R G Y

16 · September 2010
g
Wound healing

Iodine does not impair wound healing

 Also, more evidence that decreased creatinine clearance affects healing of diabetic foot ulcers
Iodine still effective
as antiseptic wound
healing agent
ata reveal that the anti-
septic effect of iodine is
not inferior to that of other
antiseptic agents and that it
does not impair the wound
healing process (J Hosp Infect
Advertorial
Nov 2010; 76(3):191-199).
In this study, investigators
evaluated 27 randomized
clinical trials, reporting on
chronic and acute wounds,
burn wounds, pressure sores,
and skin grafts. Overall, the
main outcome parameters
were wound healing, bacteri-
al count, and adverse effects.
Study results show that
iodine did not lead to a
reduction or prolongation of
wound-healing time com-
pared to other antiseptic
wound dressings or agents. In
individual trials, investigators
indicate that iodine was sig-
nificantly superior to other
antiseptic agents (such as sil-
ver sulfadiazine cream) and
non-antiseptic dressings, but
seemed inferior to a local
broad spectrum, semi-syn-
thetic, orally non-absorbable
antibiotic (rifamycin SV MMX)
and, when combined with
alcohol, to crude honey in
reducing bacterial count
and/or wound size. Adverse
effects, including thyroid
function derailment, did not
occur more frequently with
iodine.
Based on the available evi-
dence from clinical trials, the
researchers conclude that
iodine is an effective antiseptic
agent that shows neither the
purported harmful effects nor
a delay of the wound-healing
process, particularly in chronic
and burn wounds. They con-
cluded that iodine deserves to
retain its place among the
modern antiseptic agents.

The Dermatology Review Panel Creatinine clearance

affects healing of
Most physicians, pharmacists and patients appreciate the
neuropathic diabetic
rigorous regulations and safety criteria that prescription foot ulcers
medications must satisfy in order to gain approval for Canadian
use. Products that are available without a prescription,
reatinine clearance is an
however, are not subject to the same level of scrutiny and their important factor affecting
product claims are often received with both public and wound healing in patients
professional scepticism. This is the specific reason for the with neuropathic diabetic
creation of the independent Dermatology Review Panel (DRP). foot ulcers, according to new
The DRP addresses the need of manufacturers, physicians,
research (Prim Care Diabetes
pharmacists and patients to validate the legitimacy of specific
safety and efficacy claims made by non prescription products Oct. 2010; 4(3):181-185).
that affect our skin, hair or nails. The overall aim of this
Use of the phrase “doctor recommended or dermatologist recommended” has become so generic that it study, according to the
doesn’t resonate well with the increasingly more sceptical public. These tag lines do not strongly researchers, was to investi-
differentiate products and they are obtained simply through usage and attitude surveys. Products that gate the effect of creatinine
satisfy the scrutiny of The Dermatology Review Panel, on the other hand, are awarded a seal endorsing the
clearance on the short-term
legitimacy of their product claims. Products that are awarded the DRP seal display it on outer cartons,
websites, point of purchase materials, advertising etc. and are recognized along with their approved claims outcome of neuropathic dia-
on the DRP website; www.dermatologyreviewpanel.ca. Along with “in store” promotion, the DRP seal betic foot ulcers. Data from
appears on national television advertising and has obtained over 250 million household impressions. 147 neuropathic diabetic foot
The process of conducting a panel review begins by assembling a panel of dermatologists to review the ulcer episodes were included
supporting evidence and evaluate the product’s claims. To date, over 60 different Canadian dermatologists in this observational study.
have been involved in various review panels. All of the participating dermatologists are board certified
Each of the participants
members of the Canadian Dermatology Association, professors or associate professors and have specific
expertise or experience pertinent to the targeted therapeutic area. Dermatologists from every province as included in this study had
well as each of the Canadian dermatology teaching centers have been represented on our panel. been admitted to Turkey’s
Once a panel has been assembled it is divided in to two teams of three. The first team reviews the Dokuz Eylul University
product components and the product claims in 2 phases – Phase 1 the product identity and any identifying Hospital between Jan. 2003
components are blinded. If approved on the blinded bases, the reviewer proceeds to Phase 2 where the and June 2008. The
product identity and other key components are revealed.
Based on the evaluations of the first team, the submitted application, and supporting information researchers indicated that
provided, the second group of three panellists independently review and determine whether or not the patients were excluded if
product should be granted a “Seal of Approval”. they had limb ischemia.
To further eliminate bias during the review process, the identity of the reviewers is not revealed beyond Diabetic nephropathy was
the panel so as to safeguard against any potential lobbying efforts and the un-blinding of the product in investigated by 24 h urinary
review. albumin excretion and serum
Each of the panellists completes their own review working independently of each other. The reviews are
gathered and areas of concern are recorded. Dermatologists who have served as panellists express creatinine levels. Creatinine
satisfaction with this process and report directing patients to look for the seal when making retail purchases clearance was calculated
for skin products. Companies that pursue the DRP seal for their products report that the DRP seal tests according to Cockcroft-Gault
well with the public. Several dozen products have been awarded the DRP seal in validation of their claims formula. Foot ulcers were fol-
and most participating companies attempt to expand their portfolio of products bearing the DRP seal. lowed up for six months to
Lastly, to ensure that the integrity of the DRP seal is not compromised, any promotional material that
determine the outcome.
bears the DRP seal is submitted to DRP Dermatology Inc. to safeguard against mis-use. To avoid any
“grandfathering” affect, the awarded DRP seal is valid for only three years after which the process can be Overall, the short-term
repeated. This allows the panel to review any new evidence generated since the previous review and follow-up revealed that neu-
incorporate changes in any consensus treatment guidelines. For more information, visit ropathic diabetic ulcers
www.dermatologyreviewpanel.ca. healed less well in patients
with decreased creatinine
clearance than in those who
had normal creatinine clear-
ance. Of particular interest,
amputation rates were also
found to be higher in the
group with decreased creati-
nine clearance, the authors
concluded.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:11 PM Page 17

Chronicle

POSTGRADUATE
EDUCATIONAL SUPPLEMENT METHODS and the Per Protocol population. A sec-

A randomized, assessor blind, Objectives and Interventions

To compare the efficacy and tolerance
of three head lice treatment products
ondary outcome measure, louse free
rate at day 1, was determined by dry-
combing.
when used according to the manufac-
parallel group comparative efficacy trial turers instructions:
Ethics
This trial was conducted in compliance

of three products for the treatment 1. Product containing melaleuca

oil (tea tree oil) 10% w/v and lavender
oil 1% w/v (TTO/LO) (NeutraLice
with the World Medical Association
Declaration of Helsinki, the require-
ments of the National Statement on

of head lice in children:

Lotion, Key Pharmaceuticals Pty Ltd., Ethical Conduct in Research Involving
Australia) presented as a clear oily Humans, ICH E6 Guidance for the
solution Industry; Good Clinical Practice:

melaleuca oil and 2. “Suffocation” product contain-

ing benzyl alcohol, mineral oil, polysor-
Consolidated Guidance, the National
Privacy Principles and relevant
State/Territory laws. The trial activities

lavender oil, bate 80, sorbitan monooleate, Carbopol

934, water and triethanolamine
(NeutraLice Advance, Key
were approved by the Medical
Research Ethics Committee of the

pyrethrins and Pharmaceuticals Pty Ltd., Australia)

presented as a white opaque lotion
University of Queensland, project No.
2003000184 and all parents/guardians
provided written informed consent.

piperonyl butoxide, 3. Product containing pyrethrins

1.65 mg/g, and piperonyl butoxide 16.5
mg/g (P/PB) (Banlice Mousse, Johnson
Randomization
Eligible subjects were randomly

and a “suffocation”product
assigned to receive one of the three
& Johnson Pacific Pty Ltd., Australia)
head lice treatments by a computer
presented as a pressurized aerosol
generated code using blocked random-
mousse.
Stephen C Barker1 and Phillip M Altman2 ization (groups of six).
from the 1Parasitology Section, School of Chemistry & Molecular Biosciences, and UniQuest Methodology
Blinding
Pty. Ltd., University of Queensland, St Lucia, Queensland, and 2Altman Biomedical This was an assessor blind, random-
This trial was assessor-blind. The per-
Consulting Pty. Ltd., 20 Folly Point, Cammeray, New South Wales, Australia ized, parallel group, comparative
son applying the treatment could not
study. The study population consisted
ABSTRACT avoid being aware of the product being
of primary school-aged children (aged
Background: There are many different types of pediculicides available OTC in applied as the products are easily iden-
four yrs to 12 yrs) from three different
Australia. In this study we compare the efficacy and safety of three topical pediculi- tifiable by their physical attributes;
schools in Queensland and their sib-
cides: a pediculicide containing melaleuca oil (tea tree oil) and lavender oil however, assessor-blinding was
lings with live head lice (adults or
(TTO/LO); a head lice “suffocation” product; and a product containing pyrethrins achieved by using different staff for
nymphs) in their hair or on their scalp.
and piperonyl butoxide (P/PB). applications on the one hand and
If parental written informed consent
Methods: This study was a randomized, assessor-blind, comparative, parallel study of 123 assessment and CRF data entry on the
was provided, the children were
subjects with live head lice. The head lice products were applied according to the manu- other hand, and by physically separat-
screened for the presence of live head
facturer’s instructions (the TTO/LO product and the “suffocation” product were applied ing these activities at the investigation-
lice by visual inspection (see Appendix
three times at weekly intervals according to manufacturers’ instructions (on Day 0, Day 7 al site. Subjects were prevented from
1—Definitions) and by dry-combing
and Day 14) and the P/PB product was applied twice according to manufacturers’ instruc- sighting the products being used. The
(see Appendix 1—Definitions). Those
tions (on Day 0 and Day 7)). The presence or absence of live lice one day following the last parents of subjects were also blinded to
subjects meeting the entry criteria were
treatment was determined. the treatment applications. Analysts
randomized and treated with one of
Results: The percentage of subjects who were louse-free one day after the last treat- involved in data management were
the three head lice products. Subjects
ment with the product containing tea tree oil and lavender oil (41/42; 97.6%) and blinded to the identification of each
with a history of allergies, presence of
the head lice “suffocation” product (40/41, 97.6%) was significantly higher compared treatment group until the final efficacy
scalp disease, and those who were
to the percentage of subjects who were louse-free one day after the last treatment analysis for each treatment group was
treated with a head lice product in the
with the product containing pyrethrins and piperonyl butoxide (10/40, 25.0%; adj. complete.
four weeks prior to participation in this
p<0.0001). trial were excluded. Treatment of siblings
Conclusion: The high efficacy of the TTO/LO product and the head lice “suffoca- The TTO/LO and “suffocation” If an enrolled subject had a primary-
tion” product offers an alternative to the pyrethrins-based product. products were applied three times, at school aged sibling (aged four years to
Trial Registration: The study was entered into the Australian/New Zealand Clinical weekly intervals, as per the manufac- 12 years), the sibling was also exam-
Trial Registry, ACTRN12610000179033. turer’s instructions (on day 0, day 7 ined for head lice and, if infested with
,and day 14). The P/PB product was live lice and available for enrolment,
BACKGROUND reported to have an efficacy of 82.5% applied twice, as per the manufactur- this sibling was enrolled into the same
he incidence of head louse compared to a kill rate of 36.1% for a er's instructions (on day 0 and day 7). treatment arm as the subject. Those

T
infestation is high in many
countries. 1-3 This may be
explained, in part at least,
by the evolution in head
lice of lower susceptibility
(resistance) to older pediculicides. 4
Two new types of head lice products
have found wide acceptance in many
countries: essential oil based products
and products designed to “suffocate”
head lice. It is important to assess and
compare the lice kill rates and the
safety of these newer products with
existing market leading products in
well controlled and well designed
clinical trials.
One essential oil-based product
containing 11.0% eucalyptus oil was
product containing pyrethrins and
piperonyl butoxide using a study
design similar to that employed in this
study. 5 In another study a “suffoca-
tion” product containing 5% benzyl
alcohol was reported to kill all head
lice in 92.2% of subjects as measured
one day after the second treatment
(day 8). 6 Using the same head lice
product containing pyrethrins and
piperonyl butoxide, studied by our-
selves previously, as a comparator, 5
the efficacy and safety of two new
head lice products were studied by us:
NeutraLice Lotion (containing
melaleuca oil and lavender oil) and
NeutraLice Advance (a “suffocation”
product).
The louse-combing procedure normally
used in combination with these three
products was not done so we could
compare the efficacy of the compo-
nents of each product without con-
founding the efficacy measurements by
physically removing head lice by
combing (which is a treatment in
itself).
The primary outcome measure
was the louse free rate (see Appendix
1—Definitions) assessed one day after
the last treatment (at day 15 for
TTO/LO and “suffocation” products
and at day 8 after application of P/PB
product) and was determined by wet-
combing (see Appendix 1—Definitions)
for the Intention to Treat population
siblings not enrolled, because they
were unavailable for the trial for any
reason or had eggs only, were wet-
combed-out at days 0 and 7 for siblings
of subjects receiving the P/PB product
or wet-combed-out (see Appendix 1—
Definitions) at days 0, 7 ,and 14 for sib-
lings of subjects receiving TTO/LO and
“suffocation” products.
Treatment compliance
The Intent-to-Treat (ITT) population is
defined as all subjects receiving at least
Reprinted with permission from:
BMC Dermatology 2010, 10:6 © 2010
Barker and Altman; licensee BioMed
Central Ltd.
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:15 PM
POSTGRADUATE EDUCATIONAL SUPPLEMENT
Figure 1: Disposition of subjects.
one treatment application. This was
the primary population for determina-
tion of safety and efficacy.
Subjects who met all the protocol
requirements are termed the per-pro-
tocol (PP) population and this was the
secondary population for determina-
tion of efficacy. Subjects are consid-
ered to be per protocol (PP) if they
satisfied the requirements listed in
Appendix 2:
Dosage and dosage regimen
The doses, method of application and
number of weekly treatments were
those recommended by the manufac-
turers. All three products were
applied for 10 minutes. After the
TTO/LO product was applied the hair
was covered by a shower cap made of
polyvinyl chloride to retain the
volatile components of the formula-
tion. The TTO/LO and “suffocation”
Page 18
products were then washed out with
water; the P/PB product was washed
out with a standard shampoo. The
TTO/LO and “suffocation” products
were applied at weekly intervals on
days 0, 7, and 14. The P/PB product
was applied on days 0 and 7.
Criteria for evaluation
of efficacy
The efficacy of each product is
defined as the “louse-free rate.” The
louse free rate was assessed at day 1
(by dry-combing), and at day 15 (by
wet-combing) for those subjects treat-
ed with TTO/LO or “suffocation”
products OR at day 8 (by wet-comb-
ing) for those subjects treated with
the P/PB product. In the case of the
day 1 examination, dry-combing was
used and combing was stopped
immediately if live lice were
observed. A blinded assessor con-
ducted the hair and scalp examina-
tions.
Often, visual inspection was suffi-
cient to determine if live lice are pre-
sent especially in cases of severe infes-
tation. In such cases, dry/wet-combing
was not necessary to confirm the pres-
ence of live lice. However, visual
inspection alone was insufficient to
declare a subject as “louse-free.”
Criteria for evaluation of safety
(tolerance)
Subjects were interviewed on site
regarding possible adverse effects
during and immediately following
the application procedure as well as
just before the next scheduled appli-
cation by site staff. The incidence
and severity of adverse events was
compared between treatment
groups. The ITT population was
analysed for safety.
STATISTICAL AND DATA
MANAGEMENT METHODS
Determination of sample size
and data analysis
Previous efficacy studies involving the
P/PB product reported a cure rate of
36.1%4 Assuming the efficacy of the
TTO/LO and “suffocation” products to
be approximately 70% in the ITT popu-
lation, it was estimated that 40 subjects
in each group (assuming clustering,
i.e., siblings will receive the same treat-
ment as the first subject enrolled in the
family) were required to test the
hypothesis of superiority of the
TTO/LO and “suffocation” products
with a two-sided test using alpha at or
less than 0.025 to allow for two pair-
wise comparisons with 75% power. For
the unadjusted analysis the chi-square
test was used. For adjusted analysis the
Generalized Estimating Equations
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:21 PM Page 19

Table 1: Louse-free rate the day after final treatment (ITT population)

methodology was used to fit the logis- assessment. There were no subject ment, subjects in the PP population in ference in louse-free rates for TTO/LO
tic regression model to account for the withdrawals. The day after the last the TTO/LO product group were and “suffocation” products was not sta-
clustering within families. treatment was day 15 for the TTO/LO more likely to be louse-free on the day tistically significant (p=0.1009).
and "suffocation" products and day 8 after the final treatment than subjects Subjects in the PP population in the
RESULTS
for the P/PB product. in the P/PB product group (40 out of TTO/LO product group were more
Efficacy
With regard to the primary effica- 41 subjects, 97.6% vs. 10 out of 30 sub- likely to be louse-free on day 1 com-
Subjects were enrolled between April
cy endpoint for the ITT population (123 jects, 33.3%; unadj. p<0.0001). pared to subjects in the P/PB product
and June 2009. The disposition of sub-
subjects in total who were assessed Similarly, subjects in the PP popula- group (90.0% vs. 57.1%; adj. p=0.0196).
jects is shown in Figure 1; 505 subjects
after the final treatment) (Table 1), sub- tion in the “suffocation” product For the PP population on day 1, 72.4%
were screened, 132 were enrolled in
jects in the TTO/LO product group group were more likely to be louse- of the subjects in the “suffocation”
the study (43 were treated with
were more likely to be louse-free on the free on the day after the final treat- product group were louse-free, where-
TTO/LO product, 45 with “suffocation”
day after the last treatment than sub- ment than subjects in the P/PB prod- as 57.1% of the subjects in the P/PB
product and 44 with the P/PB product).
jects in the P/PB product group (41 out uct group (37 out of 37 subjects, product group were louse-free; this dif-
Of these 132 subjects (ITT population),
of 42 subjects, 97.6% vs. 10 out of 40 100.0% vs. 10 out of 30 subjects, 33.3%; ference was not statistically significant
123 subjects were evaluable: 42
subjects, 25.0%; adj. p<0.0001). In addi- unadj. p<0.0001). (adj. p=0.2986).
TTO/LO subjects; 41 “suffocation”
tion, subjects in the “suffocation” prod- With regard to the louse-free rates Demographic factors were not
product subjects and 40 P/PB subjects;
uct group were more likely to be louse- on day 1 (one day after the first appli- found to be confounders of the effect
nine subjects were not assessed at a
free than subjects in the P/PB product cation for all treatments, secondary of treatment on outcome since they
final visit. Of the 132 enrolled subjects,
group (40 out of 41 subjects, 97.6% vs. endpoint), subjects in the ITT popula- were not associated with the outcome.
108 were deemed PP; 41 TTO/LO sub-
10 out of 40 subjects, 25.0%; adj. tion in the TTO/LO product group Using a multiple logistic regression
jects, 37 “suffocation” product subjects,
p<0.0001). An analysis in which the were more likely to be louse-free on model adjusting for gender, hair
and 30 P/PB subjects. Reasons for a
nine subjects who were not assessed day 1 than subjects in the P/PB product length, hair type, school attended, and
subject being deemed not PP were:
after the final treatment, when treated group (90.3% vs. 43.3%; adj. p=0.001). accounting for clustering, there was
enrolled sibling not treated with the
as if they were non-responders, yielded Similarly, subjects in the ITT popula- still a statistically significant higher
same product as original subject; use of
similar results (Table 1). tion in the “suffocation” product group louse-free rate at the day after the
an alternative head lice treatment dur-
With regard to the secondary were more likely to be louse-free on final treatment among children treat-
ing the trial; siblings not available for
endpoint of louse-free rate for the PP day 1 than subjects in the P/PB product ed with the TTO/LO product (p-
treatment on same day as original sub-
population (108 subjects in total) group (69.4% vs. 43.3%; adj. p=0.0329). value=/<0.0001) and among children
ject; and subjects not available for
(Table 2) one day following final treat- For this population on day 1, the dif- treated with the “suffocation” product

Table 2: Louse-free rate the day after final treatment (PP population)
21683B_Skin_Allergy_Pg_:ps 10/18/2010 10:13 PM
POSTGRADUATE EDUCATIONAL SUPPLEMENT
(p-value=<0.0001) than among chil-
dren treated with the P/PB product.
Safety (tolerance)
Of the 132 subjects enrolled, 36 adverse
events were reported; 29 in relation to
TTO/LO treatment; three in relation to
“suffocation” product; and, four were
related to P/PB product treatment. All
adverse events reported were consid-
ered by the investigator to be related to
study treatment. No adverse reaction
was considered to be serious by defini-
tion. Some subjects reported more than
one adverse event - 20 TTO/LO prod-
uct-subjects (46.5%), three “suffoca-
tion” product-subjects (6.7%), and four
P/PB product-subjects (9.1%) reported
at least one adverse event.
The adverse events for the
TTO/LO, “suffocation” and P/PB prod-
ucts were rated as mild in severity with
the exception of three adverse events in
relation to the TTO/LO product which
were rated as moderate in intensity.
These three adverse events occurred in
three subjects and were described as
stinging of the eyes following product
contact with the eyes; stinging of the
neck; and, erythema of the skin. In one
case following product-contact
(TTO/LO) with the eyes, the applica-
tion was washed out prior to the 10
minute contact time. In all other cases
where an adverse event was reported
no action was taken or required.
The most commonly reported
adverse events in relation to the
TTO/LO product were stinging (13
subjects, 30.2%), flaky scalp/dry scalp
(eight subjects, 18.6%), and erythema
(four subjects, 9.3%). In the case of the
“suffocation” product, three subjects
(6.7%) reported flaky scalp/dry scalp.
In the case of the P/PB product, three
subjects (6.8%) reported flaky
scalp/dry scalp and one subject (2.3%)
reported erythema.
The reported stinging or burning
sensation associated with the TTO/LO
product (which has been reported
before with other essential oil based
head louse products)5 lasted from three
minutes to 141 minutes and erythema
was reported to last from five minutes
to 185 minutes in various subjects. Only
one case of erythema was reported with
the P/PB product and its duration was
not recorded. Flaky scalp/dry scalp,
when it occurred in relation to the
TTO/LO, “suffocation” or P/PB products
appeared to last for at least one day.
DISCUSSION
The efficacy of the P/PB product in this
study was similar to that reported for
the same product in a previous and
similarly designed study of ours (25%
as compared to 36.1%, respectively).5
The efficacy of the TTO/LO product
(97.6%), however, exceeded the efficacy
of another essential oil product studied
by us in a similarly designed study
(Moov Head Lice Solution, 82.5%).5 The
efficacy of the “suffocation” product we
tested was 97.6% compared to 92.2%
for another “suffocation” product,
which also contains 5% benzyl alcohol.6
The mechanism of action of essential
oils in the treatment of head lice is
Page 20
unknown but “suffocation” products
are thought to act by blocking the
“breathing” spiracles of lice. It has been
postulated that benzyl alcohol may
contribute to the efficacy of suffocating
products by “stunning” the spiracles
open and allowing the product to block
the respiratory apparatus.
It is likely, that the use of a show-
er cap to trap volatile components of
essential oils such as melaleuca oil and
eucalyptus oil contributes to the high-
er efficacy of these products compared
to the same products applied without
a shower cap. The use of a shower cap
with essential oil products, however,
also appears to be correlated to a
higher incidence of transient mild to
moderate stinging sensations, burning
sensations, and erythema. The sensi-
tivity of the skin of children varies.
The “suffocation” product, which is
highly efficacious yet caused little skin
irritation in the present study, would
be a good choice for children with
inherently sensitive skin.
Wet combing is a very accurate
method to diagnose active head lice
infestation. 7 In contrast to previous
studies by us, we determined efficacy
one day after the last treatment rather
than seven days after the last treat-
ment, to reduce re-infestation, which,
of course, confounds the assessment of
efficacy.8 In order to determine and
compare the safety and efficacy of the
products as they are used by parents
and children, the products were
applied strictly in accordance with the
manufacturer’s instructions. In the
case of the P/PB product there were
two applications, one week apart. In
the case of the TTO/LO and "suffoca-
tion" products there were three appli-
cations one week apart. While some
might criticise our study design, this
study design allowed us to assess the
efficacy of these products according to
the way the products will be used by
parents and children; and thus is high-
ly desirable in our opinion. It is yet to
be determined if head lice will readily
develop resistance to essential oil
products, which contain a large num-
ber of different active ingredients, and
“suffocation” products, which do not
act on the nervous system of the louse.
CONCLUSIONS
The TTO/LO product and head lice
“suffocation” product were both >97%
effective and were almost four times as
effective as the P/PB product that we
compared them with, when used
according to manufacturer instructions.
These results support the view that this
new “suffocation” product is as effective
in controlling head lice as an essential
oil product applied with a shower cap.
COMPETING INTERESTS
Associate Prof. Steve Barker and Dr.
Phillip Altman have previously pro-
vided consultant-advice to Key
Pharmaceuticals Pty. Ltd. the compa-
ny that funded this study. The compa-
ny had no active role in study design,
study management, data analysis,
interpretation of results, or manu-
script writing.
AUTHORS’ CONTRIBUTIONS head lice infestation. International
PA and SB were responsible for study Medical Publishers (UNI-MED SCIENCE),
Verlag AG, D-28323 Bremen; 2010.
design. PA was responsible for proto-
4. James S: A review of the regulation of head
col and document drafting, site staff
lice treatments in Australia.
training, study management, study [http://www.tga.gov.au/docs/pdf/headlice.pdf]
monitoring, and writing the manu- 5. Grieve KA, Altman PM, Rowe SJ, Staton
script. SB conducted the trial and JA, Oppenheim VMJ: A randomised,
helped write the manuscript. Both read double-blind, comparative efficacy
and approved the final manuscript. trial of three head lice treatment
options: malathion, pyrethrins with
ACKNOWLEDGEMENTS piperonyl butoxide and MOOV Head
Associate Professor Barker is a staff Lice Solution. Aust Pharmacist 2007;
member of the Parasitology Section, 26(9):738-743.
6. Meinking TL, Villar ME, Vicaria M,
School of Chemistry & Molecular
Eyerdam DH, Paquet D, Mertz-Rivera
Biosciences, and UniQuest Pty Ltd,
K, Rivera HF, Hiriart J, Reyna S: The
University of Queensland, Brisbane,
clinical trials supporting benzyl alco-
Queensland, Australia. Funding for the hol lotion 5% (Ulesfia): A safe and
study was provided by Key Pharma- effective topical treatment for head
ceuticals Pty. Ltd to Uniquest Pty Ltd. lice (pediculosis humanus capitis). Ped
Der 2010; 27(1):19-24.
REFERENCES 7. Jahnke C, Bauer E, Hengge UR,
1. Roberts RJ, Burgess IF: New head-lice Feldmeier H: Accuracy of diagnosis of
treatments: Hope or hype? Lancet pediculosis capitis. Arch Derm 2009;
2005; 365:8-9.
145(3):309-313.
2. Chosidow O: Scabies and pediculosis. 8. Mumcuoglu KY: Effective treatment of
Lancet 2000; 355:819-826. head louse with pediculicides. J Drugs
3. Heukelbach J: Management and control of in Derm 2006; 5(5):451.
APPENDIX 1: DEFINITIONS
• Louse-free rate
The proportion of subjects on whom no live head lice (adults or nymphs)
were found when combed by a specified method at a specified time point.
• Visual inspection
Visual inspection involves a brief examination of the hair assisted by parting of
the hair in spots to determine whether live lice are present. It may be used in
conjunction with dry-combing to determine active infestation with live lice.
• Dry-combing
Combing from scalp to the hair tips using a head lice comb and not using
water or conditioner to assist combing. Every part of the hair should be
combed with a metal-toothed lice comb up to six times. The hair may be de-
tangled with a wide-gap comb before dry-combing.
• Wet-combing
Standard commercial conditioner is applied liberally to the hair, and the hair
detangled with a regular wide-toothed comb. The hair is then combed with a
metal-toothed lice comb to remove live lice. Every part of the hair is combed six
times, scalp to hair tips. During combing, the comb is wiped onto a white tissue
and the wipings are examined for lice. After combing, the conditioner is rinsed
or towelled from the hair as desired by the subject. Wet-combing is a powerful
detection technique to determine the final infestation status of a subject at the
end of an efficacy trial, as the conditioner traps the lice making it highly unlikely
that any lice in the hair will avoid detection. Thus, the likelihood that a subject
will be incorrectly categorized as louse free when in fact a low grade infestation
still exists is substantially reduced.7 The wet-combing method results in the
smothering of lice in conditioner and the removal of head lice from the scalp,
thus wet-combing has an irreversible effect on a subject's infestation status. Wet-
combing was only used at the completion of the head lice trial.
• Wet-combed-out
“Wet-combed-out” is a therapeutic procedure which uses the wet-combining
technique (above) to ensure the hair is louse free: wet-combing is continued
until no live lice are found in six continuous passes of the comb. This is repeat-
ed for every section of the hair.
• The subject's siblings were assessed and treated, if required, as per the sec-
tion “Treatment of siblings”.
APPENDIX 2: CRITERIA FOR ASSESSING A SUBJECT AS PER PROTOCOL
• They comply with all inclusion and exclusion protocol requirements.
• Have a signed informed consent authorization.
• Treatment was administered on day 0, 7, and 14 for tea tree/lavender oil or
suffocation products or treatment was administered on days 0 and 7 for the
pyrethrins/piperonyl butoxide product.
• Are evaluated using the wet-combing procedure at one day after the final
application (day 15 in the case of tea tree/lavender ail or suffocation products
or day 8 in the case of pyrethrins/piperonyl butoxide product).
• The subject's Case Report Form is sufficiently complete to enable a valid
assessment of efficacy and safety.
• Have not used any other head lice products during the trial or in the four
weeks preceding the trial.
• Have not used any other head lice products other than those specified in
the protocol during the trial.
• Have not used a head lice comb during the trial.
• Have not bleached or dyed their hair during the trial.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:21 PM Page 21
PRESCRIBING SUMMARY
Patient Selection Criteria
INDICATIONS AND CLINICAL USE
ENBREL® is indicated for reducing signs and symptoms, inhibiting structural
damage progression and improving physical function of arthritis in adult patients
with moderate to severely active rheumatoid arthritis (RA) and psoriatic arthritis
(PsA). ENBREL can be initiated in combination with methotrexate in adult patients
or used alone in RA and PsA. ENBREL is indicated for reducing the signs and
symptoms of moderately to severely active polyarticular juvenile idiopathic arthritis
(JIA) in patients aged 4 to 17 years who have had an inadequate response to one
or more DMARDs. ENBREL has not been studied in children less than 4 years
of age. ENBREL is indicated for the treatment of adult patients with chronic
moderate to severe plaque psoriasis who are candidates for systemic therapy
or phototherapy. ENBREL is also indicated for reducing signs and symptoms of
active ankylosing spondylitis (AS).
Contraindications
ENBREL is contraindicated in patients with, or at risk of, sepsis syndrome, such as
immunocompromised and HIV+ patients, and in patients who are hypersensitive
to ENBREL or any of its components.
Special Populations
Pregnant Women
There have been no studies in pregnant women. ENBREL should not be used
during pregnancy unless benefits outweigh the risks. ENBREL has no established
use in labour or delivery.
Nursing Women
It is not known whether ENBREL is excreted in human milk or absorbed systemically
after ingestion and because of the potential of serious adverse reactions in nursing
infants from ENBREL, a decision should be made whether to discontinue nursing
or to discontinue the drug.
Pediatrics
ENBREL has not been studied in children <4 years of age. The long-term effects
of ENBREL therapy on skeletal, behavioural, cognitive, sexual and immune
maturation and development in children are unknown.
Geriatrics (older than 65 years of age)
Greater sensitivity of some older individuals cannot be ruled out. Predisposition of
older individuals to infection justifies greater caution when treating the elderly.
Safety Information
WARNINGS AND PRECAUTIONS
Serious infections leading to hospitalization or death, including sepsis,
tuberculosis (TB), invasive fungal and other opportunistic infections, have
been observed with the use of TNF blocking agents including ENBREL.
Cases of TB may be due to reactivation of latent TB infection or to new
infection.
Treatment with ENBREL should not be initiated in patients with active
infections, including TB, chronic or localized infections. Administration
of ENBREL should be discontinued if a patient develops a serious
infection or sepsis. Physicians also should exercise caution when
considering the use of ENBREL in patients with a history of recurring or
latent infections, including TB, or with underlying conditions, which may
predispose patients to infections, such as advanced or poorly controlled
diabetes. Before starting treatment with ENBREL, all patients should be
evaluated for both active and inactive (‘latent’) TB. If inactive (‘latent’)
TB is diagnosed, treatment for latent TB should be started with anti-TB
therapy before the initiation of ENBREL. Patients should be monitored
for the development of signs and symptoms of infection during and
after treatment with ENBREL, including the possible development of
tuberculosis in patients who tested negative for latent tuberculosis
infection prior to initiating therapy.
Lymphoma and other malignancies, some fatal, have been reported in
children and adolescent patients treated with TNF blockers, including
ENBREL.
Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive
fungal, viral, or other opportunistic pathogens have been reported in patients
receiving TNF blocking agents. Tuberculosis, histoplasmosis, aspergillosis,
candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis have been
reported. Patients have frequently presented with disseminated rather than
localized disease. Many of the serious infections have occurred in patients on
concomitant immunosuppressive therapy that, in addition to their underlying
disease, could predispose them to infections.
Histoplasmosis and other invasive fungal infections are not consistently recognized
in patients taking TNF blockers, including ENBREL. For patients who reside or
travel in regions where mycoses are endemic, invasive fungal infection should be
suspected if they develop a serious systemic illness.
In post-marketing studies of patients with juvenile idiopathic arthritis, serious
infections (3%) and sepsis (0.8%) have been reported.
Treatment with ENBREL and other TNF blocking agents have been associated
with rare cases of new onset or exacerbation of central nervous system disorders,
including demyelinating disorders, some presenting with mental status changes and
some associated with permanent disability. Rare cases of transverse myelitis, optic
neuritis, and new onset or exacerbation of seizure disorders have been observed
in association with ENBREL therapy.
Rare cases of neutropenia, leukopenia, thrombocytopenia, anemia and pancyto-
penia (including aplastic anemia), some with fatal outcomes, have been reported
in patients treated with ENBREL. Exercise caution in patients who have a previous
history of significant hematologic abnormalities.
In the controlled portions of clinical trials of all the TNF blocking agents, more
cases of lymphoma have been observed among patients receiving the TNF blocker
compared to control patients. RA and psoriasis patients, particularly those with
highly active disease, and/or chronic exposure to immunosuppressant therapies
may be at higher risk for lymphoma. Cases of acute and chronic leukemia have
been reported in association with post-marketing TNF blocker use in rheumatoid
arthritis and other indications. Non-melanoma skin cancer has been reported
in patients treated with TNF-antagonists, including ENBREL. Malignancies,
some fatal, have been reported among children, adolescents and young adults
(≤22 years of age) who initiated treatment with TNF blocking agents (initiation of
therapy at ≤18 years of age), including ENBREL.
The use of ENBREL in patients with Wegener’s granulomatosis receiving
immunosuppressive agents is not recommended. The use of ENBREL in any patients
receiving concurrent cyclophosphamide therapy is not recommended. Concurrent use
of ENBREL and anakinra therapies has not been associated with increased clinical
benefit to patients. Use of ENBREL with anakinra is not recommended. Concurrent
administration of abatacept and ENBREL resulted in increased incidences of serious
adverse events and did not demonstrate increased benefit; use of ENBREL with
abatacept is not recommended. When switching from one biologic to another,
patients should continue to be monitored for signs of infection.
Some patients have had allergic reactions to ENBREL.
There have been post-marketing reports of worsening of congestive heart failure
(CHF), with and without identifiable precipitating factors, in patients taking
ENBREL.
Treatment with ENBREL may result in the formation of autoantibodies and, rarely,
can result in the development of lupus-like syndrome or autoimmune hepatitis,
which may resolve following withdrawal of ENBREL.
Live vaccines should not be given concurrently with ENBREL.
Adverse Reactions
In RA patients, the most common adverse events in placebo-controlled trials were
injection site reactions (37%), infection (35%), headache (3%), dizziness (3%) and
rash (3%). Infections and malignancies were the most common serious adverse
events observed. Adverse reactions reported in JIA, adult psoriatic arthritis, AS,
and plaque psoriasis were similar to those reported in RA clinical trials.
To report any adverse events, please call 1-877-936-2735.
Administration
Dosing Considerations
ENBREL is intended for use under the guidance and supervision of a physician.
Patients may self-inject only if their physician determines that it is appropriate.
Recommended Dose and Dosage Adjustment
General
A 50 mg dose should be given as one subcutaneous (SC) injection using
either a 50 mg single-use prefilled syringe or a single-use prefilled SureClick®
Autoinjector. A 50 mg dose can also be given as two 25 mg SC injections using
the 25 mg multiple-use vial, either on the same day once weekly or three or four
days apart.
Adult RA, Psoriatic Arthritis, and Ankylosing Spondylitis Patients
The recommended dose is 50 mg per week. Methotrexate, glucocorticoids,
salicylates, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics may be
continued during treatment with ENBREL.
Adult Plaque Psoriasis Patients
The recommended starting dose is a 50 mg dose given twice weekly (administered
three or four days apart) for three months followed by a reduction to a maintenance
dose of 50 mg per week. A maintenance dose of 50 mg given twice weekly has
also been shown to be efficacious.
JIA Patients
The recommended dose for pediatric patients ages 4 to 17 years is
0.8 mg/kg per week (up to a maximum of 50 mg per week). The 50 mg prefilled
syringe or SureClick Autoinjector may be used for pediatric patients weighing
63 kg (138 pounds) or more. Glucocorticoids, nonsteroidal anti-inflammatory
drugs (NSAIDs), or analgesics may be continued during treatment with ENBREL.
Concurrent use with methotrexate and higher doses of ENBREL have not been
studied in pediatric patients.
STUDY REFERENCES
SUPPLEMENTAL PRODUCT INFORMATION
THERAPEUTIC CLASSIFICATION
Biological Response Modifier
Infections
Serious and sometimes fatal infections due to bacterial, mycobacterial, invasive fungal, viral, or other
opportunistic pathogens have been reported in patients receiving TNF blocking agents. Tuberculosis,
histoplasmosis, aspergillosis, candidiasis, coccidioidomycosis, listeriosis, and pneumocystosis
have been reported (see ADVERSE REACTIONS/Infections). Patients have frequently presented
with disseminated rather than localized disease. Many of the serious infections have occurred in
patients on concomitant immunosuppressive therapy that, in addition to their underlying disease,
could predispose them to infections.
Treatment with ENBREL should not be initiated in patients with an active infection, including
clinically important localized infections. The risks and benefits of treatment should be considered
prior to initiating therapy in patients: with chronic or recurrent infection; who have been exposed
to tuberculosis; who have resided or travelled in areas of endemic tuberculosis or mycoses, such
as histoplasmosis, coccidioidomycosis, or blastomycosis; with underlying conditions that may
predispose them to infection such as advanced or poorly controlled diabetes.
Cases of reactivation of tuberculosis or new tuberculosis infections have been observed in patients
receiving ENBREL, including patients who have previously received treatment for latent or active
tuberculosis. Patients should be evaluated according to the Canadian Tuberculosis Standards
guidelines for tuberculosis risk factors and tested for latent infection prior to initiating ENBREL
and during therapy as appropriate. Prescribers are reminded of the risk of false negative tuberculin
skin test results, especially in patients who are severely ill or immunocompromised.
If active tuberculosis is diagnosed, ENBREL therapy should not be initiated. If inactive (‘latent’)
tuberculosis is diagnosed, treatment for latent TB should be started with anti-tuberculosis therapy
before the initiation of ENBREL. In this situation, the benefit/risk balance of ENBREL therapy
should be very carefully considered. Anti-tuberculosis therapy should also be considered prior
to initiation of ENBREL in patients with a past history of latent or active tuberculosis in whom an
adequate course of treatment cannot be confirmed, and for patients with a negative test for latent
tuberculosis but having risk factors for tuberculosis infection. Consultation with a physician with
expertise in the treatment of tuberculosis is recommended to aid in the decision whether initiating
anti-tuberculosis therapy is appropriate for an individual patient.
Patients should be monitored for the development of signs and symptoms of infection during
and after treatment with ENBREL, including the possible development of tuberculosis in patients
who tested negative for latent tuberculosis infection prior to initiating therapy. Tests for latent
tuberculosis infection may be falsely negative while on therapy with ENBREL.
Tuberculosis should be strongly considered in patients who develop a new infection during
ENBREL treatment, especially in patients who have previously or recently travelled to countries
with a high prevalence of tuberculosis, or who have had close contact with a person with active
tuberculosis.
Histoplasmosis and other invasive fungal infections are not consistently recognized in patients
taking TNF blockers, including ENBREL. This has resulted in delays in appropriate treatment,
sometimes resulting in death. For patients who reside or travel in regions where mycoses are
endemic, invasive fungal infection should be suspected if they develop a serious systemic illness.
Appropriate empiric antifungal therapy may be initiated while a diagnostic workup is being performed.
Antigen and antibody testing for histoplasmosis may be negative in some patients with active
infection. When feasible, the decision to administer empiric antifungal therapy in these patients
should be made in consultation with a physician with expertise in the diagnosis and treatment
of invasive fungal infections and taking into account both the risk for severe fungal infection and
the risks of antifungal therapy.
ENBREL should be discontinued if a patient develops a serious infection or sepsis. A patient who
develops a new infection during treatment with ENBREL should be closely monitored, undergo
a prompt and complete diagnostic workup appropriate for an immunocompromised patient, and
antimicrobial therapy should be initiated, as appropriate.
In post-marketing studies of patients with juvenile idiopathic arthritis, serious infections have
been reported in approximately 3% of patients. Sepsis has also been reported in the post-market
setting (0.8%).
Neurologic Events
Treatment with ENBREL and other agents that inhibit TNF has been associated with rare cases of new
onset or exacerbation of central nervous system disorders, including demyelinating disorders, some
presenting with mental status changes and some associated with permanent disability. Rare cases
of transverse myelitis, optic neuritis, and new onset or exacerbation of seizure disorders have been
observed in association with ENBREL therapy. While no clinical trials have been performed evaluating
ENBREL therapy in patients with multiple sclerosis, other TNF antagonists administered to patients with
multiple sclerosis have been associated with increases in disease activity. Prescribers should exercise
caution in considering the use of ENBREL in patients with pre-existing or recent-onset central nervous
system demyelinating disorders. Development of new, confirmed central nervous system demyelination
in patients on ENBREL warrants consideration of discontinuation of the medication.
Hematologic Events
Rare cases (less than one case out of 1,000 patients treated) of neutropenia, leukopenia,
thrombocytopenia, anemia and pancytopenia (including aplastic anemia), some with fatal outcomes,
have been reported in patients treated with ENBREL. Cases of pancytopenia occurred as early as two
weeks after initiating ENBREL therapy. The causal relationship to ENBREL therapy remains unclear. While
the majority of patients who developed pancytopenia had recent or concurrent exposure to other anti-
rheumatic medications known to be associated with myelosuppression (e.g. methotrexate, leflunomide,
azathioprine, and cyclophosphamide), some patients had no recent or concurrent exposure to such
therapies. Although no high-risk group has been identified, caution should be exercised in patients
being treated with ENBREL who have a previous history of significant hematologic abnormalities. All
patients should be advised to seek immediate medical attention if they develop signs and symptoms
suggestive of blood dyscrasias or infection (e.g. persistent fever, bruising, bleeding, pallor) while on
ENBREL. Discontinuation of ENBREL therapy should be considered in patients with confirmed significant
hematologic abnormalities.
Patients treated with anakinra plus etanercept (3/139, 2%) developed neutropenia (ANC<1 x 109/L).
While neutropenic, one of these patients developed cellulitis, that resolved with antibiotic therapy.
Malignancies
Lymphomas
In the controlled portions of clinical trials of all the TNF blocking agents, more cases of lymphoma have
been observed among patients receiving the TNF blocker compared to control patients. In the controlled
and open-label portions of clinical trials of ENBREL in RA, AS, and PsA patients, the observed rate of
lymphoma was 0.10 cases per 100 patient-years. This is 3-fold higher than expected in the general
population. Patients with rheumatoid arthritis or psoriasis, particularly those with highly active disease
and/or chronic exposure to immunosuppressant therapies, may be at a higher risk (up to several fold) for
the development of lymphoma.
Leukemia
Cases of acute and chronic leukemia have been reported in association with post-marketing TNF blocker
use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients
with rheumatoid arthritis may be at higher risk (approximately 2-fold) than the general population for the
development of leukemia.
During the controlled portions of ENBREL trials, 2 cases of leukemia were observed among 5,445 (0.06
cases per 100 patient-years) ENBREL-treated patients versus 0 among 2,890 (0%) control patients
(duration of controlled treatment ranged from 3 to 48 months).
Among 15,401 patients treated with ENBREL in controlled and open portions of clinical trials representing
approximately 23,325 patient-years of therapy, the observed rate of leukemia was 0.03 cases per
100 patient-years.
Other Malignancies
For malignancies other than lymphoma and non-melanoma skin cancer, there was no difference in
exposure-adjusted rates between the ENBREL and control arms in the controlled portions of clinical
studies for all indications. Analysis of the malignancy rate in combined controlled and uncontrolled
portions of studies has demonstrated that types and rates are similar to what is expected in the general
population based on the Surveillance, Epidemiology, and End Results (SEER) Database of the National
Cancer Institute and suggest no increase in rates over time.
Whether treatment with ENBREL might influence the development and course of malignancies in adults
is unknown.
Non-melanoma skin cancer (NMSC)
Non-melanoma skin cancer has been reported in patients treated with TNF-antagonists, including
ENBREL. In controlled clinical trials of rheumatology (RA, AS, PsA) patients, the observed rate of NMSC
was 0.41 cases per 100 patient-years in the ENBREL-treated patients compared to 0.37 cases per
100 patient-years among control patients. In controlled clinical trials of psoriasis patients, the observed
rate of NMSC was 3.54 cases per 100 patient-years in the ENBREL-treated patients compared
to 1.28 cases per 100 patient-years among control patients. Periodic skin examination should be
considered for all patients at increased risk for NMSC. Risk factors for NMSC include cumulative exposure
to ultraviolet light, increasing age, male gender, fair complexion, history of acute sunburn or skin cancer,
tobacco use, and immunosuppressive agents.
Pediatric Patients
Malignancies, some fatal, have been reported among children, adolescents and young adults (≤22 years
of age) who initiated treatment with TNF blocking agents (initiation of therapy at ≤18 years of age),
including ENBREL. These cases were reported post-marketing and are derived from a variety of sources
including registries and spontaneous post-marketing reports. Approximately half the cases were
lymphomas, including Hodgkin’s and non-Hodgkin’s lymphoma. Of these cases, hepatosplenic T-cell
lymphoma was not reported in patients treated with ENBREL. The other cases represented a variety
of different malignancies and included rare malignancies usually associated with immunosuppression
and malignancies that are not usually observed in children and adolescents. Approximately half of
these malignancies occurred in patients being treated for inflammatory bowel disease; approximately
one-third of the cases occurred in patients being treated for JIA. The malignancies occurred after a
median of 30 months of therapy (range 1 to 84 months). Most of the patients were receiving concomitant
immunosuppressants.
In clinical trials of 696 patients treated with ENBREL, representing 1,282 patient-years of therapy, no
malignancies, including lymphoma or NMSC, have been reported.
Wegener’s Granulomatosis
In a randomized placebo-controlled study of 180 patients with Wegener’s granulomatosis, the addition
of ENBREL to standard treatment (including cyclophosphamide, methotrexate, and corticosteroids)
was no more efficacious than standard therapy alone. Patients receiving ENBREL experienced more
non-cutaneous malignancies than patients receiving placebo. The role of ENBREL in this finding is
uncertain due to imbalances between the two arms of the study including age, disease duration, and
use of cyclophosphamide. The use of ENBREL in patients with Wegener’s granulomatosis receiving
immunosuppressive agents is not recommended. The use of ENBREL in any patients receiving concurrent
cyclophosphamide therapy is not recommended.
General
Parenteral administration of any biologic product should be attended by appropriate precautions in case
an allergic or untoward reaction occurs. Allergic reactions associated with administration of ENBREL
during clinical trials have been reported in <2% of patients. If any serious allergic or anaphylactic reaction
occurs, administration of ENBREL should be discontinued immediately and appropriate therapy initiated.
Caution: The needle cap on the prefilled syringe and on the SureClick Autoinjector contains dry natural
rubber (a derivative of latex), which may cause allergic reactions in individuals sensitive to latex.
Concurrent ENBREL and anakinra treatment
Serious infections and neutropenia were seen in clinical studies with concurrent use of anakinra and
ENBREL with no added clinical benefit compared to ENBREL alone. Because of the nature of the adverse
events seen with combination of ENBREL and anakinra therapy, the combination of ENBREL and anakinra
is not recommended.
Concurrent ENBREL and abatacept treatment
In clinical studies, concurrent administration of abatacept and ENBREL resulted in increased incidences of
serious adverse events and did not demonstrate increased clinical benefit. Use of ENBREL with abatacept
is not recommended.
Switching between Biological DMARDS
When switching from one biologic to another, patients should continue to be monitored for signs of
infection.
Cardiovascular
There have been post-marketing reports of worsening of congestive heart failure (CHF), with and without
identifiable precipitating factors, in patients taking ENBREL. Physicians should exercise caution when
using ENBREL in patients who also have CHF.
Two large clinical trials (2,048 patients) evaluating the use of ENBREL in the treatment of heart failure
were terminated early due to lack of efficacy. There was a suggestion of worse heart failure outcomes in
patients with moderate to severe CHF (NYHA Class IIIB) receiving ENBREL treatment compared to patients
receiving placebo in one of the two trials.
Immune
Immunosuppression and Immunocompetence
The possibility exists for anti-TNF therapies, including ENBREL, to affect host defenses against infections
and malignancies since TNF mediates inflammation and modulates cellular immune responses. In a
study of 49 patients with RA treated with ENBREL, there was no evidence of depression of delayed-
type hypersensitivity, depression of immunoglobulin levels, or change in enumeration of effector cell
populations. The role of ENBREL in the development and course of malignancies as well as active
and/or chronic infections is not fully understood. The safety and efficacy of ENBREL in patients with
immunosuppression or chronic infections have not been evaluated.
Immunizations
Live vaccines (including yellow fever, BCG, rubella, polio, cholera, typhoid and varicella) should not be
given concurrently with ENBREL. No data are available on the secondary transmission of infection by live
vaccines in patients receiving ENBREL.
No data are available on the effects of vaccination in RA patients receiving ENBREL. Most psoriatic
21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:23 PM Page 22

arthritis patients receiving ENBREL were able to mount effective B-cell immune response to pneumococcal Placebo-Controlled Active-Controlled In controlled trials in adult patients with psoriatic arthritis, there were no differences in rates of infection
polysaccharide vaccine, but titers in aggregate were moderately lower and fewer patients had 2-fold rises Percent of patients Percent of patients among patients treated for up to one year with ENBREL and those treated with placebo, and no serious
in titers compared to patients not receiving ENBREL. The clinical significance of this is unknown. In a BODY SYSTEM Placebo Etanercept Methotrexate Etanercept infections occurred in patients treated with ENBREL.
study of 205 adult patients with psoriatic arthritis, antibody response to polysaccharide pneumococcal Preferred Term (N=152) (N=349) (N=217) (N=415) In a controlled trial in patients with ankylosing spondylitis, rates of infection were also similar to those
vaccine was similar in patients receiving placebo or ENBREL for the following antigens: 9V, 14, 18C, observed in the controlled studies of patients with RA or psoriatic arthritis. No increase in the incidence of
Hypertension 0 0 0 1
19F and 23F. serious infections was observed in patients treated with ENBREL.
Digestive System
It is recommended that JIA patients, if possible, be brought up to date with all immunizations in In clinical trials in plaque psoriasis, serious infections experienced by ENBREL-treated patients have
Nausea 3 2 18 9
agreement with current immunizations guidelines prior to initiating ENBREL therapy. Two JIA patients included cellulitis, gastroenteritis, pneumonia, abscess, osteomyelitis, viral meningitis, myositis, fascial
Diarrhea 1 1 5 7
developed varicella infection and signs and symptoms of aseptic meningitis, which resolved without infection and septic shock.
sequelae. Patients with a significant exposure to varicella virus should temporarily discontinue ENBREL Dyspepsia 0 0 3 6
In two studies in which patients were receiving both etanercept and anakinra for up to 24 weeks, the
therapy and be considered for prophylactic treatment with Varicella Zoster Immune Globulin. Mouth ulcer 0 1 11 4
incidence of serious infections was 7%. The most common infections consisted of bacterial pneumonia
Autoimmunity Constipation 1 0 3 2
(four cases) and cellulitis (four cases). One patient with pulmonary fibrosis and pneumonia died due to
Treatment with ENBREL may result in the formation of autoantibodies and, rarely, can result in the Vomiting 0 0 4 1 respiratory failure.
development of lupus-like syndrome or autoimmune hepatitis, which may resolve following withdrawal of Anorexia 0 0 2 1 In post-marketing experience, infections have been observed with various pathogens including viral,
ENBREL. If a patient develops symptoms and findings suggestive of a lupus-like syndrome or autoimmune Flatulence 0 0 2 1 bacterial, mycobacterial, fungal, and protozoal organisms. Infections, including opportunistic infections
hepatitis following treatment with ENBREL, treatment should be discontinued and the patient should be Stomatitis aphthous 0 0 2 1 (including atypical mycobacterial infection, herpes zoster, aspergillosis Pneumocystis jiroveci pneumonia,
carefully evaluated. Dry mouth 0 1 0 1 histoplasmosis, candidiasis, coccidioidomycosis, and listeriosis), have been noted and have been reported
Hepatic Stomatitis 0 0 3 0 in patients receiving ENBREL alone or in combination with immunosuppressive agents.
Hepatitis B reactivation Hemic & Lymphatic System In global ENBREL clinical studies of 20,070 patients (28,308 patient-years of therapy), tuberculosis was
Very rare cases of Hepatitis B virus (HBV) reactivation have been reported in patients treated with TNF Ecchymosis 1 0 2 2 observed in approximately 0.01% of patients. In 15,438 patients (23,524 patient-years of therapy) from
antagonists. In the majority of cases, patients were also being treated with other immunosuppressive Metabolic & Nutritional Disorders clinical studies in the US and Canada, tuberculosis was observed in approximately 0.007% of patients.
drugs, including methotrexate, azathioprine, and/or corticosteroids. Reactivation of HBV is not unique to Peripheral edema 0 0 1 2 These studies include reports of pulmonary and extra-pulmonary tuberculosis.
TNF antagonists and has been reported with other immunosuppressive drugs. Therefore, a direct causal Weight increased 0 0 1 1 In 38 ENBREL clinical trials and 4 cohort studies in all approved indications representing 27,169 patient-
relationship to TNF antagonists has not been established. Patients at risk for HBV infection should be Abnormal healing 0 0 1 0 years of exposure (17,696 patients) from the United States and Canada, no histoplasmosis infections
evaluated for prior evidence of HBV infection before initiating TNF antagonist therapy. Those identified were reported among patients treated with ENBREL. Data from clinical studies and post-marketing
Musculoskeletal System
as chronic HBV carriers (i.e. surface antigen positive) should be monitored for signs and symptoms of reports suggest that differences may exist in the risk of invasive histoplasmosis infection among TNF
Leg cramps 0 1 1 0
active HBV infection throughout the course of therapy and for several months following discontinuation blockers. Nonetheless, post-marketing cases of serious and sometimes fatal fungal infections, including
Nervous System histoplasmosis, have been reported with TNF blockers, including ENBREL.
of therapy.
Dizziness 1 3 5 5
Use in Patients with Moderate to Severe Alcoholic Hepatitis Malignancies
Vertigo 0 0 0 1
Physicians should use caution when using ENBREL in patients with moderate to severe alcoholic hepatitis. Information from 10,953 adult patients with 17,123 patient-years and 696 pediatric patients with
Respiratory System
In a study of 48 hospitalized patients treated with ENBREL or placebo for moderate to severe alcoholic 1,282 patient-years of experience across in 45 ENBREL clinical studies follows.
Rhinitis 2 2 5 4
hepatitis, the mortality rate in patients treated with ENBREL was similar to patients treated with placebo Lymphomas
Dyspnea 0 0 1 3
at one month but significantly higher after six months. Therefore, the use of ENBREL for the treatment of In the controlled portions of clinical trials of TNF blocking agents, more cases of lymphoma have been
patients with alcoholic hepatitis is not recommended. Pharyngitis 0 1 2 2
observed among patients receiving a TNF blocker compared to control patients. During the controlled
Cough increased 1 1 2 1
Carcinogenesis, Mutagenesis, and Impairment of Fertility portions of ENBREL trials in adult patients with RA, AS, and PsA, 2 lymphomas were observed among
Epistaxis 0 0 3 0 3,306 ENBREL-treated patients versus 0 among 1,521 control patients (duration of controlled treatment
Long-term animal studies have not been conducted to evaluate the carcinogenic potential of ENBREL
Voice alteration 0 0 1 0 ranged from 3 to 36 months).
or its effect on fertility. Mutagenesis studies were conducted in vitro and in vivo, and no evidence of
mutagenic activity was observed. Skin & Appendages Among 6,543 adult rheumatology (RA, PsA, AS) patients treated with ENBREL in controlled and
Rash 2 3 10 6 uncontrolled portions of clinical trials, representing approximately 12,845 patient-years of therapy, the
Use in Diabetics
Alopecia 0 1 11 5 observed rate of lymphoma was 0.10 cases per 100 patient-years. This was 3-fold higher than the
There have been reports of hypoglycemia following initiation of ENBREL in patients receiving medication
Pruritus 1 2 1 2 rate of lymphoma expected in the general population based on the SEER database. An increased rate
for diabetes, necessitating a reduction in anti-diabetic medication in some of these patients.
Urticaria 1 0 2 1 of lymphoma up to several-fold has been reported in the RA patient population, and may be further
ADVERSE REACTIONS increased in patients with more severe disease activity.
Sweat 0 0 1 1
Adverse Drug Reaction Overview Nail disorder 0 0 2 0 Among 4,410 adult psoriasis patients treated with ENBREL in clinical trials up to 36 months, representing
Adverse Reactions in Adult Patients with RA, Psoriatic Arthritis, Ankylosing Spondylitis or Special Senses approximately 4,278 patient-years of therapy, the observed rate of lymphoma was 0.05 cases per
Plaque Psoriasis Dry eye 0 0 0 1 100 patient-years, which is comparable to the rate in the general population. No cases were observed in
ENBREL has been studied in 1,442 patients with RA followed for up to 80 months, in 169 adult patients Tinnitus 0 0 0 1 ENBREL- or placebo-treated patients during the controlled portions of these trials.
with psoriatic arthritis for 24 months, in 222 patients with ankylosing spondylitis for up to 48 months and Amblyopia 0 0 1 0 Leukemia
in 1,864 patients with plaque psoriasis for up to 36 months. ENBREL has over 1,000,000 patient-years Cases of acute and chronic leukemia have been reported in association with post-marketing TNF blocker
of exposure post-market. a Includes data from the double-blinded studies in which patients received concurrent MTX therapy
b Infection (total) includes data from all three placebo-controlled trials. Body systems and relationship use in rheumatoid arthritis and other indications. Even in the absence of TNF blocker therapy, patients
Among patients with RA treated in placebo-controlled studies, serious adverse events occurred at a with rheumatoid arthritis may be at higher risk (approximately 2-fold) than the general population for the
to study drug was not collected for infections
frequency of 4% in 349 patients treated with ENBREL compared to 5% of 152 placebo-treated patients. development of leukemia.
c Non-URI and URI include data only from two placebo-controlled trials where infections were
In a subsequent study, serious adverse events occurred at a frequency of 6% in 415 patients treated
collected separately from adverse events (placebo N=110, etanercept N=213) During the controlled portions of ENBREL trials, 2 cases of leukemia were observed among 5,445
with ENBREL compared to 8% of 217 methotrexate-treated patients. Among adult patients with psoriatic
N = Number of subjects having received at least 1 dose of study drug (0.06 cases per 100 patient-years) ENBREL-treated patients versus 0 among 2,890 (0%) control patients
arthritis, serious adverse events occurred at a frequency of 4% in 101 patients treated with ENBREL
Percent = n/N*100 (duration of controlled treatment ranged from 3 to 48 months).
compared to 4% of 104 placebo-treated patients.
Less Common Clinical Trial Adverse Drug Reactions (<1%) Among 15,401 patients treated with ENBREL in controlled and open portions of clinical trials representing
In controlled trials of plaque psoriasis, rates of serious adverse events were seen at a frequency of <1.5%
The following adverse reactions were reported at an incidence of <1% (occurring in more than one approximately 23,325 patient-years of therapy, the observed rate of leukemia was 0.03 cases per
among ENBREL- and placebo-treated patients in the first 3 months of treatment. However, in patients
patient, with higher frequency than placebo): Body as a Whole: enlarged abdomen, general edema, 100 patient-years.
greater than 65 years of age treated with ENBREL 50 mg twice weekly, serious adverse events occurred
at a higher rate than in younger patients. In long-term open-label trials of plaque psoriasis, serious non- hernia, infection, injection site reaction, malaise, overdose, Sjogrens syndrome; Cardiovascular: Other Malignancies
infectious adverse events were infrequent and exposure-adjusted event rates generally remained stable cerebrovascular accident, hypotension, myocardial infarction, phlebitis, deep thrombophlebitis; For malignancies other than lymphoma and non-melanoma skin cancer, there was no difference in
throughout ENBREL treatment. Although data for patients aged 65 or greater in the long-term trials are Gastrointestinal: increased appetite, colitis, dysphagia, glossitis, gum hemorrhage, rectal hemorrhage; exposure-adjusted rates between the ENBREL and control arms in the controlled portions of clinical
limited, adverse events, including serious adverse events, occurred at a higher frequency for patients Hemic and Lymphatic System: petechia; Metabolic and Nutritional Disorders: edema, studies for all indications. Analysis of the malignancy rate in combined controlled and uncontrolled
treated with 50 mg twice weekly. hypercholesteremia, hyperglycemia; Musculoskeletal System: arthrosis, bone disorder, fibrosis portions of studies has demonstrated that types and rates are similar to what is expected in the general
tendon, bone necrosis; Nervous System: nervousness, neuropathy; Respiratory System: bronchitis, population based on the SEER database and suggest no increase in rates over time.
Among RA patients in placebo-controlled, active-controlled, and open-label trials of ENBREL, infections
lung carcinoma, hemoptysis, laryngitis; Skin and Appendages: skin carcinoma, dermatitis exfoliative,
and malignancies were the most common serious adverse events observed. Other infrequent serious Whether treatment with ENBREL might influence the development and course of malignancies in adults
skin hypertrophy, skin discoloration, skin ulcer; Special Senses: corneal lesion, ear disorder, eye
adverse events observed in RA, psoriatic arthritis, ankylosing spondylitis or plaque psoriasis clinical is unknown.
hemorrhage, otitis media; Urogenital System: cervix disorder, cystitis, dysuria, gynecomastia, uterine
trials are listed by body system: cardiovascular (cardiomyopathy, fainting, heart failure, hypertension, Non-melanoma skin cancer (NMSC)
hemorrhage, kidney polycystic, cervix neoplasm, polyuria, urine urgency.
hypotension, myocardial infarction, myocardial ischemia, deep vein thrombosis, thrombophlebitis);
Injection Site Reactions Non-melanoma skin cancer has been reported in patients treated with TNF-antagonists, including
digestive (cholecystitis, diarrhea, esophageal ulcer, gastrointestinal hemorrhage, pancreatitis,
ENBREL. Among 3,306 adult rheumatology (RA, PsA, AS) patients treated with ENBREL in controlled
appendicitis); general (impaired healing, asthenia); hematologic/lymphatic (lymphadenopathy, In controlled trials in rheumatologic indications, approximately 37% of patients treated with ENBREL
clinical trials, representing approximately 2,669 patient-years of therapy, the observed rate of NMSC
myelodysplastic syndrome, necrotizing granulomatous lymphadenitis); hepatic (hepatic disorder, developed injection site reactions. In controlled trials in patients with plaque psoriasis, approximately
was 0.41 cases per 100 patient-years vs. 0.37 cases per 100 patient-years among 1,521 control
hepatic steatosis); musculoskeletal (bursitis, fistula, fracture nonunion, polymyositis); nervous (anxiety, 14% of patients treated with ENBREL developed injection site reactions during the first three months of
patients representing 1,077 patient-years. Among 1,245 adult psoriasis patients treated with ENBREL in
cerebral ischemia, convulsion, depression, multiple sclerosis); respiratory (asthma, dyspnea, pulmonary treatment. In a long-term plaque psoriasis study, the exposure-adjusted rate of injection site reactions
controlled clinical trials, representing approximately 283 patient-years of therapy, the observed rate of
embolism, sarcoidosis); skin (worsening psoriasis); urogenital (membranous glomerulonephropathy, was 12.2 per 100 patient-years for patients treated with ENBREL 50 mg twice weekly over 96 weeks
NMSC was 3.54 cases per 100 patient-years vs. 1.28 cases per 100 patient-years among 720 control
kidney calculus). compared to 6.1 per 100 patient-years for placebo-treated patients (treated for 12 weeks). All injection
patients representing 156 patient-years.
In a randomized controlled trial in which 51 patients with RA received ENBREL 50 mg twice weekly and site reactions were described as mild to moderate (erythema and/or itching, pain, or swelling). Injection
site reactions generally occurred in the first month, if they occurred at all, did not necessitate study drug Among 89 patients with Wegener’s granulomatosis receiving ENBREL in a randomized, placebo-
25 patients received ENBREL 25 mg twice weekly, the following serious adverse events were observed
discontinuation, and subsequently decreased in frequency after the first month. The mean duration was controlled trial, five experienced a variety of non-cutaneous solid malignancies compared with none
in the 50 mg twice weekly arm: gastrointestinal bleeding, normal pressure hydrocephalus, seizure, and
three to five days. No treatment was given for approximately 90% of injection site reactions, and most receiving placebo.
stroke. No serious adverse events were observed in the 25 mg arm.
of the patients who were given treatment received topical preparations, such as corticosteroids, or oral Autoantibodies
In controlled trials, the proportion of patients who discontinued treatment due to adverse events was
antihistamines. There have been common occurrences (7%) of redness at a previous injection site when Patients had serum samples tested for autoantibodies at multiple time points. In RA Studies I and II,
approximately 4% in both the ENBREL and placebo treatment groups. The vast majority of these patients
subsequent injections were given; however, no intervention was necessary. In post-marketing experience, the percentage of patients evaluated for antinuclear antibodies (ANA) who developed new positive ANA
were treated with the recommended dose of 25 mg SC twice weekly. In plaque psoriasis studies, ENBREL
there have been reported cases (1.8% of all patients treated) of injection site bleeding and bruising (1:40) was higher in patients treated with ENBREL (11%) than in placebo-treated patients (5%). The
doses studied were 25 mg SC once or twice a week, and 50 mg SC once or twice a week. In three
observed in conjunction with ENBREL therapy. percentage of patients who developed new positive anti-double-stranded DNA antibodies was also higher
randomized, placebo-controlled studies of plaque psoriasis, the safety profile for patients receiving 50 mg
twice a week was similar to those receiving 25 mg once or twice weekly, and all were similar to placebo. Infections by radioimmunoassay (15% of patients treated with ENBREL compared to 4% of placebo-treated patients)
No cumulative toxicities were observed in long-term studies in plaque psoriasis up to 144 weeks and The percent of patients reporting infections in controlled studies of ENBREL in psoriasis, rheumatoid and by Crithidia luciliae assay (3% of patients treated with ENBREL compared to none of placebo-treated
ankylosing spondylitis up to 192 weeks. arthritis, psoriatic arthritis and ankylosing spondylitis is provided in Table 2. The most common type of patients). The proportion of patients treated with ENBREL who developed anticardiolipin antibodies was
infection was upper respiratory infection. similarly increased compared to placebo-treated patients. In Study III, no pattern of increased autoantibody
Among patients with rheumatoid arthritis in placebo-controlled studies, deaths occurred in 10 of 2,696
Table 2: Percent of Patients Reporting Infections Across Controlled Studies in Psoriasis, development was seen in ENBREL patients compared to methotrexate patients.
(0.37%) ENBREL-treated patients compared to 3 of 1,167 (0.26%) placebo-treated patients. In controlled
and uncontrolled RA studies, there were 58 deaths in 6,973 patients treated with at least one dose Rheumatoid Arthritis, Psoriatic Arthritis and Ankylosing Spondylitis The impact of long-term treatment with ENBREL on the development of autoimmune diseases is
of ENBREL over an exposure period of 11,765 patient-years (exposure-adjusted rate of 0.49). Among unknown. Rare adverse event reports have described patients with rheumatoid factor positive and/or
Psoriasis Rheumatoid Rheumatoid Psoriatic Ankylosing
patients with plaque psoriasis in placebo-controlled studies, deaths occurred in 1 of 1,245 (0.08%) erosive RA who have developed additional autoantibodies in conjunction with rash and other features
Arthritis Arthritis Arthritis Spondylitis
ENBREL-treated patients compared to 0 of 720 placebo-treated patients. In controlled and uncontrolled suggesting a lupus-like syndrome.
(Placebo- (Active-
psoriasis studies there were 10 deaths in 4,361 patients treated with at least one dose of ENBREL over Controlled) Controlled) Immunogenicity
an exposure period of 3,966 patient-years (exposure-adjusted rate of 0.25). No deaths were reported in Event Placebo ENBREL Placebo ENBREL MTX ENBREL Placebo ENBREL Placebo ENBREL Patients with RA, psoriatic arthritis, ankylosing spondylitis or plaque psoriasis were tested at multiple time
PsA, AS, or JIA studies. (N=721) (N=1,244) (N=152) (N=349) (N=217) (N=415) (N=104) (N=101) (N=139) (N=138) points for antibodies to ENBREL. Non-neutralizing antibodies to the TNF receptor portion or other protein
Adverse reactions reported in at least 1% of all patients who received ENBREL in placebo-controlled components of the ENBREL drug product were detected at least once in sera of approximately 6% of
RA trials (including the combination methotrexate trial) are outlined in Table 1 below. Adverse reactions Total 26% 30% 32% 35% 72% 64%* 43% 40% 30% 41% adult patients with RA, psoriatic arthritis, ankylosing spondylitis or plaque psoriasis. In long-term plaque
reported in juvenile idiopathic arthritis, adult psoriatic arthritis, ankylosing spondylitis, and plaque Infections psoriasis studies up to 144 weeks, the percentage of patients testing positive at any time point assessed
psoriasis trials were similar to those reported in RA clinical trials. Non-URI 17% 21% 31% 39% 60% 51% 20% 19% 20% 24% was 3%-10%. Results from JIA patients were similar to those seen in adult RA patients treated with
Table 1: Percent of RA Patients Reporting Adverse Reactions ≥1% by Body System and URI 9% 10% 16% 29%* 39% 31% 23% 21% 12% 20%* ENBREL. In all clinical studies with ENBREL to date, there has been no apparent correlation of antibody
Preferred Term in Controlled Clinical Trialsa development to clinical response or adverse events. Neutralizing antibodies have not been observed
URI=Upper Respiratory Infection
with ENBREL.
Placebo-Controlled Active-Controlled * Fisher’s exact p-value <0.05
For dose and regimen of ENBREL in each indication, please refer to Part II Clinical Trials section of the The data reflect the percentage of patients whose test results were considered positive for antibodies
Percent of patients Percent of patients
Product Monograph. to ENBREL in an ELISA assay and are highly dependent on the sensitivity and specificity of the assay.
BODY SYSTEM Placebo Etanercept Methotrexate Etanercept
Additionally, the observed incidence of any antibody positivity in an assay is highly dependent on several
Preferred Term (N=152) (N=349) (N=217) (N=415) In placebo-controlled trials in RA, psoriatic arthritis, ankylosing spondylitis, and plaque psoriasis, no factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample
Injection site reaction 10 37 7 33 increase in the incidence of serious infections was observed (approximately 1% in both placebo- and collection, concomitant medications, and underlying disease. For these reasons, comparison of the
ENBREL-treated groups). In all clinical trials in RA, serious infections experienced by patients have incidence of antibodies to ENBREL with incidence of antibodies to other products may be misleading.
Infectionb 32 35 72 64 included: pyelonephritis, bronchitis, septic arthritis, abdominal abscess, cellulitis, osteomyelitis, wound
infection, pneumonia, foot abscess, leg ulcer, diarrhea, sinusitis and sepsis. The rate of serious infections Patients with Heart Failure
Non-upper respiratory 31 39 60 51
has not increased in open-label extension trials and is similar to that observed in controlled trials (Table Two randomized placebo-controlled studies have been performed in patients with CHF. In one study,
infectionc
3). Serious infections, including sepsis and death, have also been reported during post-marketing use patients received either ENBREL 25 mg twice weekly, 25 mg three times weekly, or placebo. In a second
Upper respiratory 16 29 39 31 study, patients received either ENBREL 25 mg once weekly, 25 mg twice weekly, or placebo. Results of
of ENBREL. Some have occurred within a few weeks after initiating treatment with ENBREL. Many of the
infectionc the first study suggested higher mortality in patients treated with ENBREL at either schedule compared
patients had underlying conditions (e.g. diabetes, congestive heart failure, history of active or chronic
Other Adverse Events infections) in addition to their RA. Data from a sepsis clinical trial not specifically in patients with RA to placebo. Results of the second study did not corroborate these observations. Analyses did not identify
Body as a Whole suggest that ENBREL treatment may increase mortality in patients with established sepsis. specific factors associated with increased risk of adverse outcomes in heart failure patients treated with
Headache 3 3 13 12 ENBREL.
Table 3: Serious Infections Over Time
Asthenia 0 1 7 5 Adverse Reactions in Pediatric Patients
Abdominal pain 1 1 5 4 All ENBREL* (N=1,341)
In general, the adverse events in pediatric patients were similar in frequency and type as those seen in
Injection site 0 0 2 4 Number of subjects adult patients. Differences from adult and other special considerations are discussed in the following
Year Number of subjects Incidence rate
hemorrhage with events paragraphs.
Pain 1 0 1 1 1 1,341 46 0.034 Severe adverse reactions reported in 69 JIA patients ages four to 17 years included varicella, gastro-
Mucous membrane 0 1 2 0 2 1,088 27 0.025 enteritis, depression/personality disorder, cutaneous ulcer, esophagitis/gastritis, group A streptococcal
disorder 3 984 29 0.029 septic shock, type I diabetes mellitus, and soft tissue and post-operative wound infection.
Chills 0 0 2 0 4 865 21 0.024 Forty-three of 69 (62%) children with JIA experienced an infection while receiving ENBREL during the
Face edema 0 0 1 0 5 740 17 0.023 three months of the study (part one open-label), and the frequency and severity of infections was similar
Fever 0 0 1 0 in 58 patients completing 12 months of open-label extension therapy. The types of infections reported
6 425 7 0.016
Cardiovascular System in JIA patients were generally mild and consistent with those commonly seen in outpatient pediatric
* Controlled trials and open-label extension studies in RA. populations.
Vasodilation 1 1 1 1

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 21683B_Skin_Allergy_Pg_:ps 10/18/2010 6:23 PM Page 23

The following adverse events were reported more commonly in 69 JIA patients receiving three months
of ENBREL compared to the 349 adult RA patients in placebo-controlled trials. These included headache

Agenda
(19% of patients, 1.7 events per patient-year), nausea (9%, 1.0 events per patient-year), abdominal pain
(19%, 0.74 events per patient-year), and vomiting (13%, 0.74 events per patient-year).
In clinical studies of children with JIA, adverse events reported in those aged two to four years were
similar to adverse events reported in older children. clindamycin 1% and benzoyl peroxide 5%
In post-marketing experience, the following additional serious adverse events have been reported in
pediatric patients: abscess with bacteremia, optic neuritis, pancytopenia, neutropenia, leukopenia,
thrombocytopenia, anemia, seizures, tuberculous arthritis, urinary tract infection including urosepsis, Prescribing Summary
coagulopathy, cutaneous vasculitis, bronchitis, gastroenteritis and transaminase elevation. Other
significant adverse events have included depression. The frequency of these events and their causal 06-10 19th Congress of the
relationship to ENBREL therapy is unknown.
The long-term effects of ENBREL therapy on skeletal, behavioural, cognitive, sexual and immune
European Academy of Patient Selection Criteria
maturation and development in children are unknown. Dermatology and
A higher rate of adverse events was noted when JIA patients in an observational registry received THERAPEUTIC CLASSIFICATION: Topical Acne Therapy
ENBREL therapy in combination with methotrexate. As the juvenile idiopathic arthritis patients receiving Venereology (EADV)
INDICATIONS AND CLINICAL USE
combination therapy had more severe disease, since they had failed prior therapeutic trials with either Gothenburg, Sweden CLINDOXYL Gel (clindamycin phosphate and benzoyl peroxide) is indicated in the topical treatment of
ENBREL or methotrexate alone, it remains unclear whether the higher event rate is related to therapy or
underlying disease severity. Contact: EADV Office ¶ Tel: 322-650- moderate acne vulgaris characterised by the presence of comedones, papules and pustules. CLINDOXYL Gel is
Other not indicated for the treatment of cystic acne.
0090 ¶ Fax: 322-650-0098 ¶ Email:
In a study with etanercept manufactured by a modified process major adverse events included the
CONTRAINDICATIONS
following. Twelve subjects (5.4%) experienced 13 serious adverse events. One subject experienced
office@eadv.org CLINDOXYL Gel (clindamycin phosphate and benzoyl peroxide) is contraindicated in individuals with a
a benign lung neoplasm. One subject (0.4%) experienced a life-threatening non-infectious event history of hypersensitivity to preparations containing clindamycin or lincomycin, benzoyl peroxide, or any other
(pulmonary embolism) and 14 subjects (6.3%) experienced severe non-infectious adverse events. One component of the preparation, a history of regional enteritis or ulcerative colitis, or a history of antibiotic-
serious event (urinary tract infection) was considered infectious. One adverse event of hepatic neoplasm 13-15 4th Congress on associated colitis.
malignant (serious) and one squamous cell carcinoma (non-serious) were reported. Overall, the safety
profile was comparable to the etanercept manufactured using the previous process.
Regenerative Biology
Post-Market Adverse Drug Reactions and Medicine Safety Information
Additional adverse events have been identified during post-marketing use of ENBREL. Because these Stuttgart, Baden-Wuerttemberg,
events are reported voluntarily from a population of uncertain size, it is not always possible to reliably
estimate their frequency or establish a causal relationship to ENBREL exposure. These adverse events Germany WARNINGS
include, but are not limited to, the following (listed by body system): FOR EXTERNAL USE ONLY. NOT FOR OPHTHALMIC USE. Avoid contact with eyes and mucous membranes. In
Contact: Dr. Thomas Grieshammer ¶ the event of accidental contact with sensitive surfaces (eyes, abraded skin, mucous membranes), bathe with
Body as a Whole: angioedema, fatigue, fever, flu syndrome, generalized pain, weight gain;
Cardiovascular: chest pain, vasodilation (flushing), new-onset congestive heart failure; Digestive: Tel: 49-711-8703-54-28 ¶ Fax: 49-711- copious amounts of cool tap water.
altered sense of taste, anorexia, diarrhea, dry mouth, intestinal perforation; Hematologic/Lymphatic: 8703-54-44 ¶ Email: office@biostar-con- Orally and parenterally administered clindamycin has been associated with severe colitis which may result in
adenopathy, anemia, aplastic anemia, leukopenia, neutropenia, pancytopenia, thrombocytopenia; patient death. Use of the topical formulation of clindamycin results in absorption of the antibiotic from the skin
Hepatobiliary: autoimmune hepatitis, elevated transaminase; Immune: macrophage activation gress.de surface. Diarrhea, bloody diarrhea, and colitis (including pseudomembranous colitis) have been reported with
syndrome; Musculoskeletal: joint pain, lupus-like syndrome with manifestations including rash the use of topical and systemic clindamycin.
consistent with subacute or discoid lupus; Nervous: paresthesias, stroke, seizures and central nervous
Studies indicate that a toxin(s) produced by clostridia is one primary cause of antibiotic-associated pseudomem-
system events suggestive of multiple sclerosis or isolated demyelinating conditions such as transverse 15-17 EMAA 2010—European branous colitis. The colitis is usually characterized by severe persistent diarrhea and severe abdominal cramps
myelitis or optic neuritis; Ocular: dry eyes, ocular inflammation, uveitis; Respiratory: dyspnea,
interstitial lung disease, pulmonary disease, worsening of prior lung disorder; Skin: cutaneous vasculitis, Masters in Aesthetic & and may be associated with the passage of blood and mucous. Endoscopic examination may reveal pseu-
including leukocytoclastic vasculitis (with several symptom manifestations), erythema multiforme, domembranous colitis. Stool culture for Clostridium difficile and stool assay for C. difficile toxin may be helpful
Stevens-Johnson syndrome, toxic epidermal necrolysis, pruritus, subcutaneous nodules, urticaria, new
Anti-Aging Medicine diagnostically. When significant diarrhea occurs, the drug should be discontinued. Large bowel endoscopy
or worsening psoriasis (all sub-types including pustular and palmoplantar). Paris should be considered to establish a definitive diagnosis in cases of severe diarrhea.
DRUG INTERACTIONS
Tel: Christophe Luino ¶ Tel: 01-56-837- Diarrhea, colitis, and pseudomembranous colitis have been observed to begin up to several weeks following
Overview cessation of oral and parenteral therapy with clindamycin.
Specific drug interaction studies have not been conducted with ENBREL. ENBREL has not been formally 800 ¶ Fax: 01-56-837-805 ¶ Email: con- PRECAUTIONS
evaluated in combination with other DMARDs such as gold, antimalarials, sulfasalazine, penicillamine, tact@euromedicom.com General
azathioprine, cyclophosphamide, or leflunomide and the benefits and risks of such combinations are Concomitant topical acne treatment are not recommended because a possible cumulative irritancy effect may
unknown.
occur, especially with peeling, or abrasive agents. If severe irritation develops, discontinue use and institute
Drug-Drug Interactions 21-24 2010 ASDS (American appropriate therapy.
ENBREL can be used in combination with methotrexate in adult patients with rheumatoid arthritis or Use in Pregnancy
psoriatic arthritis. Society for Dermatologic Animal reproductive studies have not been performed with benzoyl peroxide. Reproductive studies have
No clinically significant pharmacokinetic drug-drug interactions were observed in studies with digoxin
and warfarin.
Surgery) Annual Meeting been performed in rats and mice using subcutaneous and oral doses of clindamycin ranging from 100
Chicago to 600 mg/kg/day and have revealed no evidence of impaired fertility or harm to the fetus due to
A higher rate of adverse events was noted when juvenile idiopathic arthritis patients in an observational
registry received ENBREL therapy in combination with methotrexate. As the juvenile idiopathic arthritis
clindamycin.
Contact: American Society for Animal reproduction studies have not been conducted with CLINDOXYL Gel (clindamycin phosphate and
patients receiving combination therapy had more severe disease, since they had failed prior therapeutic
trials with either ENBREL or methotrexate alone, it remains unclear whether the higher event rate is Dermatologic Surgery ¶ Tel: 847-956- benzoyl peroxide). It is not known whether CLINDOXYL Gel can cause fetal harm when administered to a
related to therapy or underlying disease severity.
0900 pregnant woman or can affect reproduction capacity. CLINDOXYL Gel should not be given to a pregnant
Patients in a clinical study who were on established therapy with sulfasalazine, to which ENBREL was woman unless the potential benefits to the mother outweigh the possible risks to the fetus.
added, experienced a statistically significant decrease in mean white blood cell counts in comparison Use in Nursing Mothers
to groups treated with either ENBREL or sulfasalazine alone. The significance of this observation is It is not known whether benzoyl peroxide or clindamycin are excreted in human milk following the
unknown. topical use of CLINDOXYL Gel. However, orally and parenterally administered, clindamycin have been
Concurrent introduction of etanercept and anakinra therapies has not been associated with increased reported to appear in breast milk. Because of the potential for serious adverse reactions in nursing
clinical benefit to patients. In a study in which patients with active RA were treated for up to 24 weeks 03-10 Dermatology Update
infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into
with concurrent ENBREL and anakinra therapy, a 7% rate of serious infections was observed, which was
higher than that observed with ENBREL alone (0%). Two percent of patients treated concurrently with
2010 account the potential benefits to the mother and the potential risks to the fetus.
ENBREL and anakinra developed neutropenia (ANC <1 x 109/L). Vancouver Pediatric Use
In a study of patients with Wegener’s granulomatosis, the addition of ENBREL to standard therapy Safety and effectiveness in the pediatric population under the age of 12 have not been established.
Contact: dermatologyupdate.com
(including cyclophosphamide) was associated with a higher incidence of non-cutaneous malignancies. Drug Interactions
Although the role of ENBREL in this finding is uncertain, the use of ENBREL in any patients receiving Clindamycin has been shown to have neuromuscular blocking properties that may enhance the action of other
concurrent cyclophosphamide therapy is not recommended. neuromuscular blocking agents. Therefore, it should be used with caution in patients receiving such agents.
In clinical studies, concurrent administration of abatacept and ENBREL resulted in increased incidences of
04-07 The 1st World Benzoyl peroxide inactivates tretinoin when used concomitantly.
serious adverse events and did not demonstrate increased clinical benefit. Use of ENBREL with abatacept Congress on Controversies ADVERSE REACTIONS
is not recommended. In controlled clinical trials where a total of 172 patients received CLINDOXYL Gel (clindamycin phosphate and
OVERDOSAGE in Plastic Surgery & benzoyl peroxide), the reported adverse events considered to have a relationship to CLINDOXYL Gel were
The maximum tolerated dose of ENBREL has not been established in humans. Dermatology (CoPLASDy) comprised mainly of reactions at the site of application such as peeling (16.3%), erythema (7.6%), dryness
STORAGE AND STABILITY
Barcelona, Spain (7.0%), burning (2.3%) and pruritus (1.7%). Mild paraesthesia and worsening of acne were noted in one
ENBREL single-use prefilled syringe, ENBREL single-use prefilled SureClick Autoinjector and ENBREL patient each.
multiple-use vial must be refrigerated at 2° to 8°C. DO NOT FREEZE. Keep the product in the original Contact: Congress Secretariat ¶ Tel: 97- Orally and parenterally administered clindamycin has been associated with severe colitis which may
carton to protect from light until the time of use. Do not shake. end fatally.
235-666-166 ¶ Email: coplas-
Do not use beyond expiration date. Cases of diarrhea, bloody diarrhea and colitis (including, rarely, pseudomembranous colitis) have been
Reconstituted solutions of ENBREL prepared with the supplied Sterile Bacteriostatic Water for Injection, dy@comtecmed.com infrequently reported as adverse reactions in patients treated with topical clindamycin (see WARNINGS).
USP (0.9% benzyl alcohol) may be stored in the original vial for up to 14 days at 2° to 8°C, with overall Abdominal pain and gastrointestinal disturbances as well as gram-negative folliculitis have also been reported
room temperature exposure of less than 12 hours during storage and handling/usage.
in association with the use of topical formulations of clindamycin.
Keep in a safe place out of the reach of children. 07-10 The 8th Asia Pacific
To report a serious or unexpected reaction to this drug, you may notify Health Canada by:
DOSAGE FORMS, COMPOSITION AND PACKAGING Congress of Allergy, Asthma Toll-free telephone: 866-234-2345
ENBREL single-use prefilled syringes are available in 50 mg (0.98 mL of a 50 mg/mL solution
of etanercept, minimum deliverable volume of 0.94 mL) dosage strength. ENBREL SureClick and Clinical Immunology Toll-free fax: 866-678-6789
Autoinjectors are available in 50 mg (0.98 mL of a 50 mg/mL solution of etanercept, minimum Singapore E-mail: cadrmp@hc-sc.gc.ca
deliverable volume of 0.94 mL) dosage strength. MedEffect website:http://www.hc-sc.gc.ca/dhp-mps/medeff/index_e.html
Each ENBREL single-use prefilled syringe and SureClick Autoinjector contains 50 mg/mL solution of Contact: Stella Chee ¶ Tel: 65-63-795- Regular mail: National AR Centre
etanercept with sucrose, sodium chloride, L-arginine hydrochloride and sodium phosphate. 259 ¶ Fax:65-64-752-077 ¶ Email: Marketed Health Products Safety and Effectiveness Information Division
ENBREL 50 mg single-use prefilled syringes and ENBREL 50 mg single-use prefilled SureClick Marketed Health Products Directorate
Autoinjectors are supplied in cartons containing four syringes or autoinjectors with 27-gauge, ½ inch admin@apcaaci2010.org Tunney’s Pasture AL 0701C
needles. A single syringe or autoinjector replacement carton is available if needed. Ottawa ON K1A 0K9
Administration of one 50 mg ENBREL prefilled syringe or 50 mg ENBREL SureClick Autoinjector provides a
dose equivalent to two 25 mg vials of lyophilized ENBREL, when vials are reconstituted and administered 11-12 4th National
as recommended.
ENBREL multiple-use vial when reconstituted with 1 mL of the supplied Sterile Bacteriostatic Water
Conference New Trends Administration
for Injection (BWFI), USP (containing 0.9% benzyl alcohol) yields a multiple-use, clear, and colourless in Paediatric Asthma
solution containing 25 mg etanercept, mannitol, sucrose, and tromethamine. CLINDOXYL Gel (clindamycin phosphate and benzoyl peroxide) should be applied to affected areas once daily
ENBREL multiple-use vial is supplied in a carton containing four dose trays. Each dose tray contains
and Allergy before bed time, after the skin has been thoroughly washed, rinsed with warm water and gently patted dry.
one 25 mg vial of etanercept, one diluent syringe (1 mL Sterile Bacteriostatic Water for Injection, USP, London
containing 0.9% benzyl alcohol), one 27-gauge, ½ inch needle, one vial adapter, and one plunger. A
Contact: Florence Doel ¶ Tel: 44-0-207-
Supplemental Product Information
single dose replacement tray is available, if needed.
SYMPTOMS AND TREATMENT OF OVERDOSAGE
See Product Monograph for complete prescribing information. 501-6761 ¶ Fax: 44-0-207-978-8319 ¶ Symptoms
Product Monograph available upon request. Please call 1-877-936-2735 Topically applied clindamycin phosphate formulations can be absorbed in sufficient amounts to produce systemic effects (see WARNINGS). If medication is
Email: flo.doel@markallengroup.com applied excessively, marked redness and peeling may occur. There are no reports of human ingestion overdosage with CLINDOXYL Gel (clindamycin phosphate
Manufactured by Immunex Corporation, Thousand Oaks, CA 91320, U.S.A.
Distributed by Amgen Canada Inc. and Wyeth Canada. and benzoyl peroxide).
Treatment
ENBREL® is a registered trademark of Immunex Corporation and SureClick® is a registered trademark of
Amgen Inc., all used with permission.
19-20 Hair and Scalp If ingested orally, no specific antidote is available. Simple gastric lavage should be performed. Treatment should be symptomatic.
AVAILABILITY OF DOSAGE FORMS
© 2010 Wyeth Canada, a Pfizer company, and Amgen Canada. All rights reserved. Diseases in Dermatological CLINDOXYL Gel (clindamycin phosphate and benzoyl peroxide) is available in a 45 g tube, and a 5 g sample tube.

Practice: International PRODUCT MONOGRAPH AVAILABLE UPON REQUEST

Course and Symposium ® Trade-mark

Protected by patent CA2142530
Warsaw, Poland Stiefel Canada Inc.
6635 Henri Bourassa West
Contact: Lidia Rudnicka ¶ Tel:0-48-225- Montreal, Quebec
H4R 1E1
081-480 ¶ Fax:0-48-225-081-492 ¶ SCI/D/09-05/CDXL/1172/PI-E
www.stiefel.ca Control No: 089202
Email:lidiarudnicka@yahoo.com

Please turn to Agenda page 25

PM EDE-HELP-PI1-CSA 3pg indd 3

21683B_Skin_Allergy_Pg_:ps 10/18/2010
24 · September 2010
Acne: Involve GP/FP if oral contraceptives indicated
potential side effects,” says
Dr. Gidon, noting minocy-
cline can trigger joint pain,
hepatitis, or inflammation of
the liver, as well as photo-
sensitivity.
Dr. Gidon notes mild
acne characterized by come-
dones and blackheads can
be treated by topical treat-
ments such as salicyclic acid
and tretinoin creams, and
advises patients to use non-
comedogenic make-up and
skin care products in such
cases.
If patients present with
acne that features papules
and pustules, she would
suggest they use topical
antibiotics. Dr. Gidon sees a
role for Isolaz in patients
who are not responding to
topical tretinoins or
systemic antibiotics.
Depend ing how the acne
presents, she uses photody-
namic therapy with a photo-
sensitizing drug combined
with light.
“If the acne is more
severe, we would talk about
Isolaz and chemical peels in
addition [to other therapies],”
says Dr. Gidon. “We would
consider doing facials and
extractions and cleaning out
the pores.”
Hormonal therapy an option
Oral isotretinoin would be a
last choice because of its side
effect profile, according to Dr.
Gidon. “Patients have to be
closely monitored if they are
on [oral isotretinoin],” says
Dr. Gidon, adding it is strictly
used as a monotherapy to
treat acne.
Oral isotretinoin com-
monly causes chapped lips,
can affect the liver, and is ter-
atogenic, so is contraindicat-
ed in pregnancy, and there
are even what have been
called idiosyncratic cases of
patients having suicidal
thoughts.
Once acne is under con-
trol, facials and Isolaz treat-
ment are effective mainte-
nance therapy for patients,
adds Dr. Gidon. Many
patients may find their acne
in remission once they are
out of their adolescence.
Hormonal therapy is an
option for adolescent girls
and women who have acne
that is cyclical with their
menstrual cycle, say clini-
cians. The pattern of hormon-
al acne is that it usually pre-
sents on the lower face. Dr.
Gidon would check patients
6:23 PM Page 24
THE CHRONICLE of S K I N & A L L E R G Y
for a cluster of symptoms “I like family physicians to extended use of oral contra- One area of research in
such as obesity, bad acne, be involved with the treat- ceptives. skin care that is “interesting,”
hair growth, and irregular ment, and for them to pre- When patients have notes Dr. Jang, is topical
menstrual cycle, that may be scribe the oral contracep- active acne as well as acne estrogens. Topical estrogens
suggestive of polycystic ovari- tives. I think the family scars, it’s preferable to get offer the promise of reversing
an syndrome. physicians should be the active acne under control the effects of aging in older
Dr. Gidon says referring a involved because of the before trying to treat any patients and potentially a
patient to that patient’s fami- potential side effects.” depressed acne scars, says condition like acne in
ly physician would be the “Contraceptives and Dr. Jang. Once the acne is younger patients.
course of action she would testosterone agonists like under control, then fraction- “People want to use
take if oral contraceptives spironolactone can help in ated lasers or IPL are treat- more topical [medications]
are indicated to manage the management of acne,” ment choices. than systemic [therapies],”
acne. notes Dr. Jang. There are “You can use IPL or says Dr. Jang.
“If it [the patient’s acne] risks with oral contraceptives laser,” says Dr. Jang. “Fract- “We are talking about the
occurs premenstrually, I such as blood clots, with the ionated devices are the latest, face, which is a small area,
would recommend oral con- risk of such serious adverse and they do not require a lot so topical therapy would be a
traceptives,” says Dr. Gidon. events increasing with of down time.” good fit.”
in humans is unknown. The anaerobic or hypoxic conditions
that might lead to the production of genotoxic compounds are
unlikely to occur in topical use. There is no conclusive evidence
after 30 years of clinical use of systemic metronidazole for either
metronidazole topical gel a genotoxic or carcinogenic potential.
One percent, Once a day Hematologic
Metronidazole is a nitroimidazole and should be used with care
in patients with evidence of, or history of, blood dyscrasia.
Ophthalmologic
Prescribing Summary Avoid contact with the eyes. Topical metronidazole has been
reported to cause tearing of the eyes. It should not be used in or
close to the eye. If contact does occur, flush with water.
Conjunctivitis associated with topical use of metronidazole on
Patient Selection Criteria the face has been reported.
Sensitivity/Resistance
THERAPEUTIC CLASSIFICATION: Topical Anti-Rosacea Agent Exposure to excessive sunlight, including sunlamps and tanning
beds, should be avoided when using MetroGel, MetroCream,
INDICATIONS AND CLINICAL USE
or MetroLotion.
MetroGel® (0.75% & 1%), MetroCream® (0.75%), and MetroLotion®
(0.75%) (metronidazole topical gel, cream, and lotion) are Skin
indicated for: If a reaction suggesting local irritation occurs, patients should be
• topical application in the treatment of inflammatory papules, pustules, directed to use the medication less frequently, discontinue use
and erythema of rosacea. Patients with dry or sensitive skin may temporarily, or discontinue use until further instructions.
prefer using the cream or lotion formulation (i.e., MetroCream There were no reports of contact dermatitis attributed to
MetroGel and MetroCream, during clinical trials. However,
or MetroLotion).
there have been reports of contact dermatitis/allergic reaction
Geriatrics (* 65 years of age): reported during MetroLotion clinical trials and as post marketing
While specific clinical trials in the geriatric population have not
adverse reactions (see Adverse Reactions section). Physicians
been conducted, 66 patients aged 65 years and older treated with should be aware of the possibility of skin sensitivity reactions
MetroGel 1% over 10 weeks showed comparable safety and efficacy and of cross-sensitization with other imidazole preparations,
as compared to the general study population. such as clotrimazole and tioconazole.
Pediatrics:
Safety and effectiveness in pediatrics have not been established. Special Populations
CONTRAINDICATIONS Pregnant Women
MetroGel, MetroCream, and MetroLotion are contraindicated: There has been no experience to date with the use of MetroGel,
• in individuals with a history of hypersensitivity to metronidazole, MetroCream, or MetroLotion in pregnant patients. Metronidazole
crosses the placental barrier and enters the fetal circulation rapidly.
or other ingredients of the formulations. For a complete listing,
No fetotoxicity was observed after oral metronidazole in rats or
see the Dosage Forms, Composition and Packaging section of the
Product Monograph. mice. However, because animal reproduction studies are not always
predictive of human response, this drug should only be used during
pregnancy after careful assessment of the risk/benefit ratio.
Safety Information Nursing Women
Even though metronidazole blood levels are significantly lower after
WARNINGS AND PRECAUTIONS topical application than after oral administration a decision should
be made whether to discontinue nursing or to discontinue the drug,
General taking into account the importance of the drug to the mother. After
Because of the minimal absorption of metronidazole, and oral administration, metronidazole is secreted in breast milk in
consequently its insignificant plasma concentration after topical concentrations similar to those found in the plasma.
administration, the systemic adverse reactions reported with
ADVERSE REACTION SERIOUSNESS AND INCIDENCE
the oral form of the drug should not be expected with MetroGel,
MetroCream, or MetroLotion (metronidazole topical gel, cream, Adverse Drug Reaction Overview
or lotion). The safety profile of MetroGel (metronidazole topical gel 0.75%
Physicians should consider the most appropriate formulation and 1%), MetroCream (metronidazole topical cream 0.75%)
(gel, cream, or lotion) for their patients. and MetroLotion (metronidazole topical lotion 0.75%) has been
Although rosacea is a chronic disease, data on the long-term established in clinical trials. The results of the safety analyses
use of MetroGel, MetroCream, or MetroLotion in rosacea is not indicate topical application of metronidazole is well tolerated.
available. In controlled clinical trials, patients were treated for up to Clinical Trial Adverse Drug Reactions
12 weeks (see Administration section). Because clinical trials are conducted under very
Carcinogenesis and Mutagenesis specific conditions the adverse reaction rates observed in the
Information from preclinical studies indicates that metronidazole clinical trials may not reflect the rates observed in practice
and its principal metabolite are mutagenic in bacteria and that and should not be compared to the rates in the clinical trials of
tumours were observed in animal studies after oral administration another drug. Adverse drug reaction information from clinical
of metronidazole (see Toxicology section of Product Monograph). trials is useful for identifying drug-related adverse events and
The relevance of these findings to the topical use of metronidazole for approximating rates.
 21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:17 PM Page 25

THE CHRONICLE of S K I N & A L L E R G Y September 2010 · 25

Agenda: Medical meetings of note, around the world

Continued from page 23 55-68-06-261 ¶ Fax: 421-55-68-06-156 ¶ Malignancy Update Annual Conference of the ¶ Fax: 39-055-283-686 ¶ Email: winter-
Email: lenka.cuperova@progress.eu.sk San Diego, Calif. American Society for Laser academy@heventogroup.com or
DECEMBER 2010
Contact: Conference Secretariat ¶ Tel: Medicine and Surgery l e o n a r d o . f r o n t i c e l l i
02-04 Excellence in 09-12 COSMODERM XVI - 858-652-5400 ¶ Fax: 858-652-5565 ¶ Grapevine, Tex. @heventogroup.com
Paediatrics 2010 The International Aesthetic Email: med.edu@scrippshealth.org Contact: American Society for Laser
London Dermatology Congress of Medicine and Surgery, 2100 Stewart 17- 19 Dermatology,
Contact:Malvina Nezi ¶ Tel: 30-210- the European Society for FEBRUARY 2011 Avenue, Suite 240, Wausau, Wis. Internal Medicine, and
688-9164 ¶ Fax: 30-210-684-4777 ¶ Cosmetic & Aesthetic 54401 ¶ Tel: 715-845-9283 ¶ Fax: 715- Surgery Up to Date
Email:excellence@candc-group.com Dermatology (ESCAD) 04-08 69th Annual
Meeting of the American 848-2493 ¶ Email: informa- Hanoi, Viet Nam
Dresden, Germany tion@aslms.org Contact: Dr. D. Czarnecki ¶ Tel: 613-
02-04 XI. Congress of the Contact: Isabelle Lärz ¶ Tel: 49-3641-
Academy of Dermatology
New Orleans, La. 988-70066 ¶ Fax :613-988-70044 ¶
Slovak Society of Aesthetic 3533-2702 ¶ Fax: 49-3641-3533-21 ¶
Contact: American Academy of APRIL 2011 Email: dbczarnecki@gmail.com
and Cosmetic Dermatology Email: cosmoderm2010@conventus.de
Dermatology ¶ Tel: 202-842-3555 ¶
with International 07-10 Winter Academy of
Fax: 202-842-4355 28-30 1st International
Participation JANUARY 2011 Dermatology
Lucerne, Switzerland
Cosmetology and
Zilina, Slovakia 15-16 Melanoma 2011: MARCH 2011 Cosmetic Gynecology
Contact: Conference Secretariat:
Contact: Congress Secretariat ¶ Tel: 421- 21st Annual Cutaneous Congress
March 30- April 03 2011 Hevento Group ¶ Tel: 39-055-210-454
Istanbul, Turkey
Contact: Ozge Tagizade ¶ Tel: 00-905-
304-066-011 ¶ Fax: 00-903-124-396-802 ¶
Metronidazole Topical Gel 1% Metronidazole Topical Cream
Email: info@kozmetikjinekoloji.com
In a 10-week controlled clinical trial in patients with rosacea, In controlled clinical trials with MetroCream (metronidazole
557 patients used MetroGel (metronidazole gel) 1% and topical cream), the patient safety database included 71 evaluable
189 patients used the gel vehicle once daily. Among the treatment patients. Adverse reactions attributed to the use of MetroCream are
groups, the adverse reactions considered related to treatment were
low with comparable frequencies. The majority of the adverse
summarized in the table below.
Table 3: Adverse Reactions Attributed to MetroCream
CDF awards
reactions were mild or moderate in severity.
Adverse reactions considered related to once daily treatment
SYSTEM ORGAN CLASS /
ADVERSE REACTIONS
INCIDENCE
(NO. OF PATIENTS)
SEVERITY FOLLOW-UP TREATMENT announced
with MetroGel 1% were reported at a frequency of <1% and are
summarized in the table below.
Skin and subcutaneous disorders
Skin discomfort 2.8% (2) moderate none required
during CDA
Table 1: Adverse Reactions Attributed to MetroGel 1% †
SYSTEM ORGAN CLASS / INCIDENCE SEVERITY FOLLOW-UP TREATMENT
(burning & stinging)
Rosacea 1.4% (1)
moderate
mild
drug discontinued
drug discontinued
in St. John’s
ADVERSE REACTIONS (NO. OF PATIENTS) (NO. OF PATIENTS)
Erythema 1.4% (1) moderate drug discontinued Continued from page 12
Skin and subcutaneous tissue disorders
Skin irritation 1.4% (1) moderate drug discontinued
Dry skin 0.9% (5) mild (2) treatment required Dr. Denis Sasseville
mild none required Pruritus 1.4% (1) moderate none required McGill University, Montreal
mild none required*
moderate none required** CDF-Johnson & Johnson Professional
Metronidazole Topical Lotion Dermatology Research Grant $25,000
Erythema 0.7% (4) moderate (3) none required* During controlled clinical trials with MetroLotion (metronidazole
severe treatment required* Edwin Brown-CDA Endowment-CDF
topical lotion), the patient safety database included 72 evaluable Research Grant $20,000
Pruritus 0.5% (3) mild none required* patients. Adverse reactions attributed to the use of MetroLotion are
moderate none required* Prediction of disease outcome in
summarized in the following table.
severe treatment required* cutaneous T cell lymphoma based on
Skin burning 0.2% (1) mild none required** gene expression
Table 4: Adverse Reactions Attributed to MetroLotion
sensation
SYSTEM ORGAN CLASS / INCIDENCE SEVERITY FOLLOW-UP TREATMENT
Skin irritation 0.2% (1) severe treatment required* ADVERSE REACTIONS (NO. OF PATIENTS) Dr. Jerry Shapiro
Rash papular 0.4% (2) mild none required University of British Columbia,
Skin and subcutaneous disorders
moderate none required* Vancouver
Hypersensitivity 2.8% (2) moderate drug discontinued
Skin desquamation 0.2% (1) moderate none required* CDF-Janssen-Ortho Research Grant
Dermatitis contact 1.4% (1) mild therapy interrupted $50,000
Skin tightness 0.4% (2) mild none required** temporarily
CDF Benefactor Life Members’
Facial oedema 0.2% (1) severe treatment required* 1.4% (1) moderate drug discontinued
Research Grant $5,000
Urticaria 0.2% (1) moderate treatment required* Erythema 2.8% (2) mild none required Antigenic determinants of alopecia
Eye Disorders 2.8% (2) moderate drug discontinued areata
Conjunctivitis 0.4% (2) mild treatment required Rosacea 1.4% (1) mild drug discontinued
mild treatment required* Dr. Haishan Zeng
Eye irritation 0.2% (1) mild none required
Post-Market Adverse Drug Reactions University of British Columbia,
Gastrointestinal Disorders Vancouver
Since commercialization of MetroGel (0.75%, 1%), MetroCream and
Dyspepsia 0.2% (1) mild treatment required MetroLotion, the following post marketing adverse reactions have CDF-Graceway Canada Research
† MedDRA version 9.0 has been used for coding of adverse reactions. been reported. Grant $25,000
* drug discontinued Combining confocal imaging and
A causal relationship with topical metronidazole has not been
** therapy interrupted/reduced
unequivocally established for these adverse drug reactions. raman spectroscopy for non-invasive
skin cancer detection and margin
Metronidazole Topical Gel 0.75% Post Marketing Adverse Drug Reactions by System Organ delineation
The patient safety database included 114 evaluable patients that Class, MedDRA preferred term for MetroGel, MetroCream and
participated in controlled and uncontrolled MetroGel trials. Adverse MetroLotion:
reactions attributed to the use of MetroGel are summarized in the Dr. Jianhua Zhao
table below. Blood and lymphatic disorders: Leucopenia University of British Columbia,
Eye disorders: Lacrimation increased Vancouver
Table 2: Adverse Reactions Attributed to MetroGel 0.75%
Gastrointestinal disorders: Dysgeusia, nausea CDF-Abbott Research Grant $50,000
SYSTEM ORGAN CLASS / INCIDENCE SEVERITY FOLLOW-UP TREATMENT
ADVERSE REACTIONS (NO. OF PATIENTS) General disorders and administration: Condition aggravated Two-photon absorption for targeted
Skin and subcutaneous disorders Immune system disorders: Hypersensitivity skin evaluation and phototherapy: a
Nervous system disorders: Paraesthesia pilot study
Skin irritation 1.8% (2) mild none required
Dry skin 1.8% (2) mild none required Skin and subcutaneous tissue disorders: Dermatitis contact, dry
skin, erythema, pruritis, rash pustular, dermatitis bullous, skin Dr. Youwen Zhou
Erythema 1.8% (2) mild none required University of British Columbia,
burning sensation, skin irritation
Burning sensation 0.9% (1) mild none required Vancouver
Eye disorders CDF-Galderma Canada Research
Grant $25,000
Lacrimation 0.9% (1) mild none required
increased Gene expression profiles of vitiligo
lesional skin: correlation with clinical
subtypes and therapeutic response

3:43 PM
21683B_Skin_Allergy_Pg_:ps 10/18/2010
26 · September 2010
EB patients may benefit from risky stem cell procedure
marrow transplantation, it is a
high-risk therapeutic
approach that could shorten
the expected survival of
patients with recessive dys-
trophic epidermolysis bul-
losa, particularly those with
less severe clinical manifesta-
tions,” the researchers
warned in the paper.
Nevertheless, the results
warrant further study of stem-
cell–based approaches for
patients who have the sever-
est forms of epidermolysis
bullosa, the researchers said.
In an accompanying edi-
torial, Dr. Leena Bruckner-
Tuderman, of the University
of Freiburg, Germany, called
the study a “leap forward”
that provides hope of an
effective treatment in genetic
skin diseases.
But Dr. Bruckner-
Tuderman cautioned about the
subjective assessment of clini-
cal symptoms in the trial and
the naturally undulating course
of the disease that may have
accounted for some of the
results “due to a long period of
careful medical attention, pro-
tection from trauma, and stan-
dardized wound care.”
Helps painful course of EB
The study initially included
seven children with recessive
dystrophic epidermolysis bul-
losa, which is caused by loss-
of-function mutations in
COL7A1. This gene encodes
for collagen type VII (C7),
which is localized at the junc-
tion between dermis and epi-
dermis as a major compo-
nent of the fibrils that anchor
the two layers together.
These 14.5- to 15-month-
old children already had
extensive blistering with vary-
ing degrees of involvement of
other organs.
The disease causes
painful erosions and blisters
from birth on, eventually often
leading to esophageal stric-
tures, mutilating scars, joint
contracture, fusion of fingers
and toes, and aggressive
squamous-cell carcinomas.
Based on promising
mouse model results, the
researchers used immuno-
myeloablative chemotherapy
to condition the children for
transplantation of allogeneic
stem cells. But the study,
however, was not without
adverse effects.
One patient died during
6:23 PM Page 26
this conditioning as a result of
hemorrhagic cardiomyopathy,
which the researchers suggest-
ed was likely due to cardiotoxi-
city of cyclophosphamide.
Of the six patients who
made it to transplantation,
five received unfiltered mar-
row stem cells from an
human leukocyte antigen
(HLA)-identical sibling. One
of the five also got umbilical-
Drug Interactions
Table 5: Established or Potential Drug-Drug Interactions
Metronidazole Ref
Coumarin and C/CT
warfarin
Alcohol T (topical)
C (oral)
Other imidazole T Skin sensitivity
preparations such
as clotrimazole
and tioconazole
Legend: C = Case Study; CT = Clinical Trial; T = Theoretical
To report an adverse event, contact your Regional Adverse
Reaction Monitoring Office at 1-866-234-2345 or contact:
GALDERMA CANADA INC., 105 Commerce Valley Dr. W., Suite 300,
Thornhill, Ontario, L3T 7W3.
33127 GAME XXXX_MetroGel PI_E2 3
cord blood from the same
sibling donor.
The sixth patient couldn’t
get the marrow infusion as
scheduled because of severe
chemotherapy-related toxici-
ty and instead received
umbilical-cord blood from an
unrelated donor.
The one patient who
required a second transplant
because of graft rejection
Effect Clinical comment
Potentiate the Drug interactions are less likely
anticoagulant with topical administration but
effect should be kept in mind when
metronidazole is prescribed
for patients who are receiving
anticoagulant treatment. Oral
metronidazole has been reported
to potentiate the anticoagulant
effect of coumarin and warfarin
resulting in a prolongation of
prothrombin time.
Disulfiram-like Oral metronidazole also
reaction interacts with alcohol,
producing a disulfiram-like
reaction. Although this adverse
reaction has not been reported
with topical application of
metronidazole, a drug interaction
of metronidazole-alcohol is
a possibility.
Physicians should be aware of
the possibility of skin sensitivity
reactions and of cross-
sensitization with other imidazole
preparations.
THE CHRONICLE of S K I N & A L L E R G Y
recovered by hematopoietic three patients by parent reports
measures but then died from and clinical observation;
infection on day 183. • Reduced bandage use
Clinical benefits seen in one patient at six months
with the treatments included: and another at one year com-
• Increased wound heal- pared with pretransplanta-
ing and reduced mucocuta- tion; and
neous blistering in the first • Improved rate of wound
100 days after treatment in all healing and marked reduc-
patients; tions in oral mucosal lesions
• Reduced percentage of by parent report for all patients.
body-surface area affected in The researchers also
Administration
Recommended Dose and Dosage Adjustment
MetroGel 1% (metronidazole topical gel 1%): Apply and rub in
a thin film once daily to entire affected area(s).
MetroGel 0.75%, MetroCream 0.75%, AND MetroLotion 0.75%
(metronidazole topical gel, cream and lotion): Apply and rub
in a thin film twice daily, morning and evening, to entire
affected areas.
Significant therapeutic results should be noticed within
three weeks. Clinical studies have demonstrated continuing
improvement through nine weeks of therapy. The dosage
required for long-term administration is uncertain (see
Warnings and Precautions section).
Administration
Areas to be treated should be cleansed before application of
MetroGel, MetroCream, or MetroLotion. The face must be dry
before applying medication.
Patients may use cosmetics after application of MetroGel,
MetroCream, or MetroLotion. The medication should have absorbed
into the skin (“dry”) before the cosmetics are applied.
Overdosage
There is no human experience with overdosage of MetroGel,
MetroCream, or MetroLotion. Topically applied metronidazole can
be absorbed in sufficient amount to produce systemic effects.
Massive ingestion may produce vomiting and slight disorientation.
There is no specific antidote. Ipecac syrup or gastric lavage; then
activated charcoal followed by a saline cathartic is suggested.
Treatment should include symptomatic and supportive therapy.
Product Monograph is available upon request.
GALDERMA CANADA, INC.
105 Commerce Valley Dr. W., Suite 300
Thornhill, Ontario L3T 7W3
60
metronidazole topical gel
E583-1107
8/26/10 10:13:44 PM
21683B_Skin_Allergy_Pg_:ps 10/21/2010 8:11 AM Page 27

THE CHRONICLE of S K I N & A L L E R G Y September 2010 · 27

Message from the Medical Editor

found increased C7 deposition at the
dermal–epidermal junction in five of
the six patients, though without nor-
malization of anchoring fibrils.
All six transplant recipients showed
substantial proportions of donor cells in
the skin (median 20%) without
detectable antibodies against C7.
These results affirm that even
partial correction of C7 deficiency can
improve skin and mucosal integrity,
the researchers concluded.
The possible benefits need to be
weighed against the risks, the
researchers noted.
The treatment-related toxicity
included grade 3 mucositis in all six
patients; transient, clinically significant
hyperbilirubinemia in four patients;
renal insufficiency requiring three
days of hemodialysis for fluid man-
agement in two patients; and oppor-
incorporate these therapies into our
tunistic infections in three patients.
practice. For example, we have validat-
Long-term risks of the procedure, ed a global system for scarring that may be a useful tool if used in combina-
which couldn’t be assessed in this tion with other scoring tools such as DLQI and validated acne scoring systems
analysis, may include SCC. to evaluate outcomes of our therapy.
Dr. Wagner’s group said they and It is essential that we have evidence-based therapies, otherwise we risk
other groups are already considering being viewed as but “one step ahead of the Avon person” (to quote one of my
ways to improve the safety of the pro- Mayo Clinic trained internists).
cedure, such as coinfusion of mes- Again I would like to highlight and acknowledge the important role of the
enchymal stromal cells or reduced- Canadian Dermatology Foundation (CDF) in funding significant Canadian
dose conditioning. One of the limita- research (see page 12 for a list of the research award winners, and their area
tions of the study included the small of study). I was honored to have received the Dr. George S. Williamson
number of patients. Research Grant. It is an extremely valuable resource in helping us to continue
our work on the heritability of familial psoriasis and comorbidities in
Copyright MedPage Today, LLC. All Newfoundland and Labrador.
rights reserved. Reprinted with per- —Wayne P. Gulliver, MD, FRCPC
mission. www.medpagetoday.com Medical Editor

of the body be treated at a time. Topical corticosteroids should be used with pituitary-adrenal function, resulting in secondary adrenal in-
sufficiency and manifestations of hypercorticoidism, including
caution on lesions of the face, groin and axillae as these areas are more Cushing’s disease. Recovery is usually prompt and complete
prone to atrophic changes than other areas of the body. If skin atrophy oc- upon steroid discontinuation. In cases of chronic toxicity, slow
withdrawal of corticosteroids is recommended.
ˆ
curs, discontinue treatment. There may be a risk of rebound psoriasis when
discontinuing corticosteroids after prolonged periods of use (see ADVERSE AVAILABLE DOSAGE FORMS
Dosage Form: Ointment (faintly translucent white to yellow-
REACTIONS). ish ointment).
Strength: 50 μg/g calcipotriol and 0.5 mg/g betamethasone
MONITORING AND LABORATORY TESTS (as dipropionate).
Treatment with Dovobet® in the recommended amounts (See DOSAGE AND Packaging: Available in 60 g and 120 g lacquered aluminium
Prescribing Summary ADMINISTRATION) does not generally result in changes in laboratory values. tubes (equipped with an aluminium membrane).
Store at 5° to 25°C. For easy application: do not refrigerate
In patients using greater than the recommended weekly maximum of 100 g
(this is to prevent rubbing and pulling of delicate skin).
of Dovobet®, patients at risk of hypercalcemia, and patients with marginally Use within 12 months of first opening the tube. Product
elevated serum calcium levels, serum calcium should be monitored at suitable monograph available upon request.

Patient Selection Criteria
THERAPEUTIC CLASSIFICATION
Topical Antipsoriatic Agent Vitamin D Analogue/Corticosteroid
INDICATIONS AND CLINICAL USE
Dovobet® ointment is indicated for the topical treatment of psoriasis vulgaris
for up to 4 weeks. Dovobet® should not be used on the face.
SPECIAL POPULATIONS
Pregnant Women: The safety of calcipotriol and/or topical corticosteroids for
use during pregnancy has not been established. Although studies in experi-
mental animals have not shown teratogenic effects with calcipotriol, studies
with corticosteroids have shown teratogenic effects. The use of Dovobet® is
not recommended in pregnant women.
Nursing Women: The safety of calcipotriol and/or topical corticosteroids for
use in nursing women has not been established. It is not known whether
calcipotriol can be excreted in breast milk or if topical application of corti-
costeroids can lead to sufficient systemic absorption to produce detectable
quantities in breast milk. The use of Dovobet® is not recommended in nursing
women.
Pediatrics (<18 years of age): There is no clinical trial experience with the
use of Dovobet® in children. Children may demonstrate greater susceptibility
to systemic steroid-related adverse effects due to a larger skin surface area
to body weight ratio as compared to adults.
CONTRAINDICATIONS
Known hypersensitivity to any of the ingredients of Dovobet® ointment. NOT
FOR OPHTHALMIC USE. Not for the treatment of viral, fungal or bacterial skin
infections, tuberculosis of the skin, syphilitic skin infections, chicken pox,
eruptions following vaccinations, and in viral diseases such as herpes sim-
plex, varicella and vaccinia.
Safety Information
WARNINGS AND PRECAUTIONS
General
Due to the content of calcipotriol, hypercalcaemia may occur if the maximum
weekly dose (100 g) is exceeded. Serum calcium is quickly normalised when
treatment is discontinued. The risk of hypercalcaemia is minimal when the
recommendations relevant to calcipotriol are followed (see Monitoring and
Laboratory Tests).
intervals.
For further information, please contact Medical Information at
MOST COMMON ADVERSE REACTIONS LEO Pharma Inc. 1-800-263-4218.
®
In clinical trials, the most common adverse reaction associated with Dovobet® Registered trademark of LEO Pharma A/S used under
license and distributed by LEO Pharma Inc., Thornhill, ON.
was pruritus. Pruritus was usually mild and no patients were withdrawn from
treatment. Calcipotriol is associated with local reactions such as transient
lesional and perilesional irritation.
Rare cases of hypersensitivity reaction have been reported.
To report an adverse reaction please notify Health Canada at
1-866-234-2345 or LEO Pharma Inc. at 1-800-263-4218. LEO Pharma Inc. Thornhill, Ontario L3T 7W8
www.leo-pharma.com/canada
DRUG INTERACTIONS
There is no experience of concomitant therapy with other antipsoriatic drugs.
Administration
Dosing Considerations
Dovobet® is FOR TOPICAL USE ONLY. Not for ophthalmic use. There is no
clinical trial experience with the use of Dovobet® in children.
Recommended Dose and Dosage Adjustment
Dovobet® should be applied topically to the affected areas once daily for up
to 4 weeks. After satisfactory improvement has occurred, the drug can be
discontinued. If recurrence takes place after discontinuation, treatment may
be reinstituted.
The maximum recommended adult dose of Dovobet® ointment is 100 g per
week.
SUPPLEMENTAL PRODUCT INFORMATION
OTHER POTENTIAL ADVERSE REACTIONS
Prolonged use of corticosteroid-containing preparations may produce striae or atrophy of the skin or subcuta-
neous tissues. Topical corticosteroids should be used with caution on lesions of the face, groin and axillae as
these areas are more prone to atrophic changes than other areas of the body. If skin atrophy occurs, discontinue
treatment.
Topical corticosteroids can cause the same spectrum of adverse effects associated with systemic steroid ad-
ministration, including adrenal suppression. Adverse effects associated with topical corticosteroids are generally
local and include: dryness, itching, burning, local irritation, striae, atrophy of the skin or subcutaneous tissues,
telangiectasia, hypertrichosis, folliculitis, skin hypopigmentation, allergic contact dermatitis, maceration of the
skin, miliaria, or secondary infection. If applied to the face, acne rosacea or perioral dermatitis can occur. In addi-
tion, there are reports of the development of pustular psoriasis from chronic plaque psoriasis following reduction
or discontinuation of potent topical corticosteroid products.
SUPPLEMENTAL SAFETY INFORMATION
Carcinogenesis
Calcipotriol when used in combination with ultraviolet radiation (UVR) may enhance the known skin carcinogenic
effect of UVR. (See TOXICOLOGY, Carcinogenicity, in the Product Monograph).

The safety of calcipotriol and/or topical corticosteroids for use with children
or pregnant or lactating women has not been established. (See SUPPLE-
MENTAL SAFETY INFORMATION; Special Populations).
Skin
Dovobet® should not be used on the face since this may give rise to itching
and erythema of the facial skin. Patients should be instructed to wash their
hands after each application of Dovobet® in order to avoid inadvertent trans-
fer to the face. Should facial dermatitis develop in spite of these precautions,
Dovobet® therapy should be discontinued.
Endocrine and Metabolism
Application on large areas of damaged skin, under occlusive dressings, or in skin folds should be avoided since it
increases systemic absorption of corticosteroids and the risk of adverse effects such as adrenal suppression with
the potential for glucocorticosteroid insufficiency after withdrawal of treatment. Manifestations of Cushing’s syn-
drome, hyperglycaemia and glucosuria can also be produced in some patients by systemic absorption of topical
corticosteroids. Occlusive dressings should not be applied if body temperature is elevated.
All of the adverse effects associated with systemic use of corticosteroids, including adrenal suppression, may
also occur following topical administration of corticosteroid-containing products such as Dovobet®, especially in
children.
Missed Dose
If a dose is missed, the patient should apply Dovobet® as soon as he/she remembers and then continue on
as usual.

Prolonged use of corticosteroid-containing preparations may produce striae Overdosage

Due to the calcipotriol component of DOVOBET (calcipotriol and betamethasone dipropionate), excessive admin-
or atrophy of the skin or subcutaneous tissues. Therefore, it is recommended istration (i.e. more than the recommended weekly amount of 100 g) may cause elevated serum calcium, which
that corticosteroid treatment be interrupted periodically, and that one area rapidly subsides when treatment is discontinued. In such cases, it is recommended to monitor serum calcium
levels once weekly until they return to normal. Excessive or prolonged use of topical corticosteroids can suppress
21683B_Skin_Allergy_Pg_:ps 10/20/2010
28 · September 2010
New acne scale: Quicker, does not involve counting scars
ing of acne (J Cutan Med Surg
Jul-Aug 2010; 14(4):156-160).
The aim of this investiga-
tion was to develop and vali-
date a global scale for acne
scar severity inclusive of the
trunk and the face, indicated
Dr. Jerry Tan, a Windsor, Ont.,
dermatologist and adjunct
professor in the department of
medicine
at the
University
o f
Western
Ontario,
London,
and the
study’s
l e a d
Dr. Jerry Tan
investiga-
tor.
“This
n e w
develop-
ment of


SCAR-S is
unique
because
w h i l e
Dr. Wayne
there is
Gulliver
one other
global
acne scar

Toxicology – Reproduction section of the Product Monograph).
system
that does
n o t 65 years and older to determine whether they respond differently from younger
involve

SFOBM

PS
DBSEJBD
GVODUJPO


lesion
counting,
the pri- Dr. Charles Lynde
m a r y
motive for its development
was to direct corrective pro-
cedures. In that system,
severity was based on scar
morphology, visibility from
social distances, and adequa-
cy of coverage by hair or
makeup,” Dr. Tan said.
Assess scarring on face, trunk
“Previous acne scar assess-
ment methods have been pri-
marily used to assess the
face, but what matters to
patients is that we evaluate
the face and trunk because
this is where the scarring
occurs,” indicated Dr. Charles
Lynde, assistant clinical pro-
fessor, University of Toronto
and consultant at the
University Health Network,
Toronto Western and
Markham-Stouffville
Scarborough Hospital.
During the investigation Dr.
Lynde noted that researchers
from several sites in Canada
used the SCAR-S assessment
to evaluate acne scar severity
and patient-reported scar
severity to see if there was a
correlation and they found the
10:17 PM Page 28
THE CHRONICLE of S K I N & A L L E R G Y
correlation was high. regions was 55%, 24%, and scales for the evaluation of THE CHRONICLE OF SKIN & ALLERGY.
Findings reveal that 73% 14%, respectively. acne scarring, the SCAR-S Dr. Lynde agrees that
of 973 subjects reported acne Data further suggested that does not involve counting of SCAR-S is a practical and vali-
scarring. Overall, the self- acne severity correlated with acne scars. In addition, SCAR- dated global system for acne
assessment of scarring was SCAR-S (p<0.001) for the back S is also inclusive of the chest scar evaluation, which can be
associated with facial SCAR-S (r=0.612), the chest (r=0.548), and back,” Dr. Tan said. used by other dermatologists-
and overall SCAR-S scores and the face (r=0.514). Acne “The SCAR-S acne assess- not only in Canada, but
(p<0.001, r=0.31 and 0.30, duration correlated with ment is practical and easy to use around the world. There is no
respectively). In all, acne scar- patient-reported severity of and absolutely no problem to other validated scale for acne
ring was observed at the face scarring (r=0.244) and overall incorporate as part of the acne scarring that is based on how
in 87%, the back in 51%, and SCAR-S scores (r=0.152). scarring assessment,” said Dr. clinicians perform these evalu-
the chest in 38%. Clinically rel- Clinically relevant scarring Wayne Gulliver, chair, Discipline ations in practice.
evant scarring (mild or increased with acne duration. of Medicine, Memorial University “This direct evaluation
greater) at each of these “Unlike most pre-existing of Newfoundland and editor of SCAR-S method is probably
Hepatic
Silkis™ is not recommended in patients with reduced liver function.
Renal
Silkis™ is not recommended in patients with mild to moderate renal impairment.
Skin
Hands should be washed after applying Silkis™ in order to avoid unintentional
application to other areas. In case of severe irritation or a contact allergic
reaction, treatment with Silkis™ should be discontinued.
Prescribing Summary Special Populations
Pregnant Women:
5IFSF
BSF
OP
BEFRVBUF
BOE
XFMMDPOUSPMMFE
TUVEJFT
JO
QSFHOBOU
XPNFO
although studies in experimental animals have not shown teratogenic effects.
Patient Selection Criteria Silkis™ should be used during pregnancy only if the anticipated benefit clearly
outweighs the potential risk (see Toxicology - Reproduction section of the
Product Monograph).
THERAPEUTIC CLASSIFICATION:
Topical Non-Steroidal Antipsoriatic Agent Nursing Women:
It is not known whether calcitriol is excreted in human milk. Silkis™ has
INDICATIONS AND CLINICAL USE
been found in the milk of lactating rats. Calcitriol should be used by nursing
Silkis™ (calcitriol) ointment 3 μg/g is indicated for: women only if the anticipated benefit clearly outweighs the potential risk (see
t

5PQJDBM
USFBUNFOU
PG
NJME
UP
NPEFSBUF
QMBRVF
UZQF
QTPSJBTJT
QTPSJBTJT
WVMHBSJT
with up to 35% body surface area involvement. Geriatrics (>65 years of age):
Geriatrics (>65 years of age): Of the total number of subjects in clinical studies of Silkis™, 14% were 65 and
Clinical studies of Silkis™ ointment did not include sufficient numbers of subjects over. The incidence of drug-related adverse events, serious adverse events, and
adverse events leading to discontinuation were higher in subjects 65 or older
subjects. than in subjects 18 to <65. In general, use in elderly patients should be cautious,
Pediatrics (<18 years of age): SFnFDUJOH
UIF
HSFBUFS
GSFRVFODZ
PG
EFDSFBTFE
IFQBUJD
Silkis™ is not recommended for pediatric use. Safety and effectiveness in pediatric and of concomitant disease or other drug therapy.
patients have not been established. Pediatrics (<18 years of age):
There are insufficient data in patients under 18 years of age to determine the
CONTRAINDICATIONS
t

1BUJFOUT
XIP
BSF
IZQFSTFOTJUJWF
UP
UIJT
ESVH
PS
UP
BOZ
JOHSFEJFOU
JO
UIF
GPSNVMBUJPO

safety and efficacy in this population. Silkis™ is not recommended in pediatric
patients.
or component of the container. For a complete listing, see the Dosage Forms,
Composition and Packaging section of the product monograph. Monitoring and Laboratory Tests
Serum calcium levels should be monitored at regular intervals if risk factors for
t

NOT FOR OPHTHALMIC or INTERNAL USE.
hypercalcemia are present. If serum calcium becomes elevated, treatment with
t

1BUJFOUT
XJUI
IZQFSDBMDFNJB
BOE
QBUJFOUT
LOPXO
UP
TVGGFS
GSPN
BCOPSNBM
DBMDJVN
calcitriol should be discontinued.
metabolism.
t

1BUJFOUT
PO
TZTUFNJD
USFBUNFOU
PG
DBMDJVN
IPNFPTUBTJT ADVERSE REACTION SERIOUSNESS AND INCIDENCE
Adverse Drug Reaction Overview
t

Patients with severe renal impairment or end-stage renal disease.
The clinical trial adverse reaction data for Silkis™ is largely based on two
8-week randomized, vehicle-controlled trials as well as one long-term
(1-year) safety study. These data provide information on twice-daily exposure in
Safety Information 743 patients, including 239 exposed for 6 months and 116 exposed for at least
one year. The most common adverse reactions experienced were laboratory test
WARNINGS AND PRECAUTIONS abnormality, skin discomfort, pruritus, and psoriasis.
General
Serum calcium levels should be monitored at regular intervals if risk factors for Post-Market Adverse Drug Reactions
Because post-market adverse drug reactions are reported voluntarily from a
hypercalcemia are present. If the serum calcium level becomes elevated, calcitriol
therapy should be discontinued and the serum calcium level monitored in these population of uncertain size, it is not always possible to reliably estimate their
patients until it returns to normal. Due to the potential effect of Vitamin D and its GSFRVFODZ
PS
FTUBCMJTI
B
DBVTBM
SFMBUJPOTIJQ
UP
ESVH
FYQPTVSF
metabolites on calcium metabolism, substances that may increase the absorption of The following post-market adverse reactions have been reported with the use
calcitriol must not be added to the ointment or used concomitantly with the ointment. of Silkis™ ointment: acute blistering dermatitis, erythema, pruritus, skin burning
sensation, and skin discomfort. Two serious, unexpected related reports have
Silkis™ ointment must not be covered with an occlusive dressing.
been received which describe skin atrophy (1) and blisters over the body,
Silkis™ is not recommended for severe, extensive psoriasis (i.e., involvement of burning sensation, and extensive flare-up of weepy eczema (2).
more than 35% of the body surface).
Silkis™ should not be applied to the eyes, lips or facial skin. DRUG INTERACTIONS
™ Overview
Silkis is not indicated for use in other clinical forms of psoriasis.
Silkis™ (calcitriol) ointment 3 μg/g must be used with caution in patients
No more than 30 g of Silkis™ ointment should be used per day. receiving medications known to increase serum calcium levels, such as thiazide
Carcinogenesis and Mutagenesis diuretics, or medications with pharmacological effects impacted by a change in
Animal data suggest that the vehicle of Silkis™ ointment may enhance the ability of calcium levels, such as digoxin. Caution must also be exercised in patients
ultraviolet radiation (UVR) to induce skin tumours (see Toxicology - Carcinogenicity receiving calcium supplements or high doses of vitamin D.
section of the Product Monograph). Patients who apply Silkis™ ointment to exposed Silkis™ has a slight irritant potential, and therefore it is possible that concomitant
skin should avoid excessive exposure of the treated areas to either natural or use of peeling agents, astringents, or irritant products may produce an additive
artificial sunlight, including tanning booths and sun lamps. Physicians may wish to irritant effect.
limit or avoid using phototherapy in patients who use Silkis™ ointment.
Drug-Food Interactions
Endocrine and Metabolism Interactions with food have not been established.
If abnormal serum calcium levels are observed, treatment with calcitriol should
be discontinued.
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:17 PM Page 29

THE CHRONICLE of S K I N & A L L E R G Y September 2010 · 29

going to enhance the recogni-

tion of more severe acne
rather than discounting the pri-
Psoriasis: Depression, suicide more common
mary lesions,” Dr. Lynde said. important—you can imagine the point where they are able psychiatric disorders because
“Scarring is something that conditions. We have to a 25- to 30-year-old person to cope,” Dr. Joordens they represent substantial
certainly happens with acne understand that this is a seri- with psoriasis who may wish added. morbidity that can be
and that is why dermatologists ous thing and it could be to they did not have psoriasis The study authors indi- improved with a variety of
treat acne to decrease the the point where a teenager and it may embarrass them a cated in their report that it is pharmacologic and non-phar-
overall lesions and decrease could have suicidal little but they have gotten to important to identify these macologic approaches.
the potential for scarring. thoughts,” said Steve “We cannot be certain it
“Presently SCAR-S is not Joordens, PhD, a professor of is psoriasis that causes these
esearchers also indicated the

R
actively used, but should be as psychology at the University patients to have these higher
a measure of the permanent of Toronto in Scarborough, hazard ratio of depression was rates of depression, anxiety,
effect. Few clinicians and Ont. and suicide. Co-morbid
researchers actively evaluate “As we age I think we put higher among patients with issues such as alcohol use,
the extent of scarring from less emphasis on how we severe psoriasis. decreased socio-economic
acne,” Dr. Tan concluded. look. Yes, looks are still status, and other factors may
play a role as well,” Dr.
Gelfand said.
Recent data suggest that
psychiatric co-morbidity may
Drug-Herb Interactions Table 1: Summary of Drug-related Adverse Events (at least 1%) of the Two Pooled Vehicle-Controlled Studies
have negative affect response
Interactions with herbal products have not been established. Calcitriol ointment 3 μg/g (n=419) Calcitriol vehicle ointment (n=420)
to certain psoriasis treat-
Drug-Laboratory Interactions Total number of AEs 58 71
Interactions with laboratory tests have not been established. ments (e.g., pho-
Total number of subjects 36 (8.6%) 45 (10.7%)
To report an adverse event, contact your Regional Adverse Reaction Monitoring with AEs tochemotherapy), while
Office at 1-866-234-2345 or contact: GALDERMA CANADA INC., 105 Commerce SKIN AND APPENDAGES other studies suggest that
Valley Dr. W., Suite 300, Thornhill, Ontario, L3T 7W3. Discomfort skin 11 (2.6%) 9 (2.1%) control of psoriasis is associ-
Pruritus 6 (1.4%) 4 (1%) ated with improvements in
LAB TEST ABNORMAL
Administration psychological symptoms, the
Lab test abnormality 14 (3.3%) 15 (3.6%) study authors wrote.
Dosing Considerations In these two studies, among subjects having laboratory monitoring, hypercalcemia (albumin-adjusted calcium Further studies are nec-
t

4JMLJT™ is for TOPICAL USE ONLY and not for oral, ophthalmic or intravaginal use. above the upper limit of normal) at any post-baseline point during the 8-week trials, was observed in 24% (18/74)
of calcitriol-exposed subjects compared to 16% (13/79) of vehicle-exposed subjects. No subject had an albumin- essary to determine the
t

5IFSF
JT
OP
DMJOJDBM
USJBM
FYQFSJFODF
XJUI
UIF
VTF
PG
4JMLJT™ in children and there adjusted calcium result over the alert level (10% above the upper limit of the normal range) at any time-point
mechanisms by which psori-
throughout the study. Hypercalcemia was not reported as an adverse event during either study.
is limited experience with the use of Silkis™ in the elderly (see Warnings and
Precautions). A one-year multi-center, open-label, non-comparative study enrolled 324 patients with psoriasis. Silkis™ was applied asis is associated with
twice daily for up to 52 weeks. The most common adverse events were laboratory test abnormality (8%), urine test
t

4JMLJT™ should be used in pregnant or nursing women only if the benefit versus abnormality (4%), psoriasis (4%), flu syndrome (4%), hypercalciuria (3%), pruritus (3%), and skin infection (3%). There depression, anxiety, and sui-
were 10 cases (3%) of hypercalcemia (defined as an albumin-adjusted serum total calcium concentration above the
risk is favourable (see Warnings and Precautions). upper limit of the reference range (2.15 to 2.55 mmol/L). With one exception (2.72 mmol/L), all other albumin-adjusted cidality as well as approach-
serum total calcium concentrations were less than 5% above the upper limit of normal. There were 3 subjects with
t

4JMLJT™ is contraindicated in patients with severe renal impairment or end-stage reported kidney stones.
es to prevent such adverse
renal disease. Less Common Clinical Trial Adverse Drug Reactions (<1%) outcomes in patients with
Skin and Appendages: psoriasis (0.2%)
t

4JMLJT™ is not recommended in patients with mild to moderate renal impairment psoriasis, the authors con-
or in patients with liver dysfunction (see Warnings and Precautions). OVERDOSAGE
The accidental ingestion of Silkis™ (calcitriol) ointment 3 μg/g may produce symptoms that are consistent with vitamin cluded.
Recommended Dose and Dosage Adjustment D toxicity and hypercalcemia. The initial clinical signs (polyuria, polydypsia, dyspepsia) should be confirmed with a
serum analysis of calcium levels prior to initiating treatment for hypercalcemia.
Silkis™ (calcitriol) ointment 3 μg/g should be applied to the areas affected with
Topically applied calcitriol can be absorbed in sufficient amounts to produce systemic effects. If signs of hypercalcemia
psoriasis twice daily, morning and evening, after washing and gentle drying. No occur with the prescribed use of Silkis™, treatment should be discontinued.
more than 30 g of Silkis™ ointment should be used daily. No more than 35% of the Product monograph is available upon request.
body can be treated.
Reference: 1. PrSilkis™ Ointment Product Monograph, Galderma Canada Inc., March 9, 2010.
No additional therapeutic benefit has been demonstrated with higher doses or more GALDERMA CANADA, INC.
GSFRVFOU
BQQMJDBUJPO 105 Commerce Valley Dr. W., Suite 300
Thornhill, Ontario L3T 7W3
Missed Dose
If a dose of Silkis™ is missed, it should be applied as soon as the patient remembers Amgen Canada/
and further dosing resumed as usual.
Wyeth Canada
Administration
The affected area should be washed and dried gently. The ointment should be Enbrel . . . . 4-5, 21-23
applied and rubbed in gently until the medication is no longer visible. The treated Enliven . . . . . . . . . . . 2
area should not be bandaged or occluded in any way. E675-0510

Hands should be washed thoroughly with soap and water after each application. Astellas Pharma Canada
After satisfactory improvement has occurred, the drug should be discontinued. Protopic . . . . . . . . . . . 10
If recurrence takes place after discontinuation, the treatment may be reinstituted.
STORAGE AND STABILITY
Store at room temperature (15° - 30° C).
Bayer Inc.
DOSAGE FORMS, COMPOSITION AND PACKAGING
Finacea . . . . . . . . . . . 30
Silkis™ (calcitriol) ointment 3 μg/g is available in collapsible aluminium tubes
coated internally with an epoxy-phenolic resin and fitted with a white high-density Daniele Henkel
polyethylene or polypropylene screw cap. Tubes contain 5 g or 60 g of ointment. Corporate . . . . . . . . .8
Silkis™ is a white, translucent, ointment containing 3 μg/g (0.0003% w/w) of
calcitriol. Other components of the ointment are vitamin E (dl-a tocopherol) added
as an antioxidant, mineral oil, and white petrolatum. Dermatology
Review Panel
SUPPLEMENTAL PRODUCT INFORMATION Corporate . . . . . . . .16
Clinical Trial Adverse Drug Reactions
Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical
trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of
another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse
Galderma Canada
events and for approximating rates. MetroGel . 12, 15, 24-26
Silkis™ was studied in two vehicle-controlled 8-week studies with 419 patients treated with Silkis™ twice daily. Drug-
related adverse reactions that occurred in at least 1% of patients in the Silkis™ group are shown in the following table: Silkis . . . . . . . 7, 28-29

La Roche-Posay
Effaclar DUO . . . . . .31

LEO Pharma Inc.

Dovobet . . . . . . . . 9, 27
Fucidin . . . . . . . . . . . 11

Stiefel, a GSK company

Clindoxyl . .14, 32, 23
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:17 PM Page 30

30 · September 2010
Journal Club THE CHRONICLE of S K I N & A L L E R G Y

Research of Note Diagnostic Quiz

NITRIC OXIDE RELEASING CREAM EFFECTIVE IN TINEA VERSICOLOR
ata suggests that nitric oxide (NO) releasing cream appears to be effective in the treat-
ment of tinea versicolor. A total of 64 patients (31 males and 33 females) participated in
this double-blind, randomized, placebo-controlled clinical trial. Overall, participants were
older than 10 years with a clinical diagnosis of tinea versicolor and positive KOH preparation, and
were divided in two groups: active and control (32 individuals in each). The authors indicated that
participants were randomized to receive either nitric oxide (NO)-liberating cream as the active
group and placebo as the control. There was significant improvement with acidified nitrite cream
in the active group after 10 days (p=0.000). The findings indicated that there no significant differ-
ence was found between the two groups in terms of severity, age and sex distribution.
Jowkar F, Jamshidzadeh A, Pakniyat S, Namazi MR: Efficacy of nitric oxide-liberating cream on
pityriasis versicolor, in the Journal of Dermatology Treatment 2010 Mar; 21(2):93-96.
A. Acute febrile neutrophilic dermatosis (Sweet’s syn-
HIGH DOSES OF UVB MAY DECREASE BLOOD FOLATES IN PSORIASIS PATIENTS drome)
esearchers indicate high doses of broadband ultraviolet radiation (UVB) phototherapy B. Pyoderma gangrenosum
may slightly decrease blood folates in psoriasis patients. The overall aim of this study was C. Erythema multiforme
to investigate the influence of solar radiation, sunbeds and/or broadband UVB photothera-
py on the levels of serum and erythrocyte folate in patients with psoriasis, or healthy volunteers. invite your participation in this
Serum and erythrocyte folate status in patients with psoriasis and healthy volunteers was mea- regular feature of the journal.
sured before and after exposure to solar radiation, broadband UVB, or use of sunbeds. In some Please send all images and
cases plasma homocysteine and serum 25-hydroxyvitamin D (25(OH)D) were also measured. In correspondence to: Medical Editor,
all, serum and erythrocyte folate levels in healthy volunteers and in psoriasis patients were not The Chronicle of Skin & Allergy
influenced to any statistically significant extent after exposure to solar radiation, to single or to mul- 555 Burnhamthorpe Road, Suite 306,
tiple UV treatments. However, a slight decay of blood folates and an increase of plasma homocys- Toronto, Ont. M9C 2Y3.
teine levels were observed in psoriasis patients after exposure to UV radiation. Exposure to sun or
sunbeds does not have any significant effect on the levels of blood folate of healthy humans. matosis (Sweet’s syndrome)
Juzeniene A, Stokke KT, Thune P, Moan J: Pilot study of folate status in healthy volunteers and in Correct answer: Acute febrile neutrophilic der-
patients with psoriasis before and after UV exposure, in the Journal of Photochemistry and
Image courtesy Makis et al: Journal of Medical Case Reports 2010; 4:281. The electronic
Photobiology 2010 Nov. 3;101(2):111-116. version of this article is the complete one and can be found online at:
http://www.jmedicalcasereports.com/content/4/1/281. © 2010 Makis et al; licensee
BioMed Central Ltd.

What THE LAY PRESS is saying about . . .

USE OF UV NAIL LAMPS RISKY
In the New York Times, dermatologists
caution readers about an often over-
looked source of ultraviolet radiation
(UV) that is emitted from many nail
lamps found in almost all nail salons
and sold widely for use at home (Aug.
2, 2010).
The news source indicated that
although there are no large studies to
support skin cancer risk related to UV
nail lamps, a study published last year
in the Archives of Dermatology
described two cases of healthy middle
aged women without family histories of
skin cancer who developed non-
melanoma skin cancers on their hands.
It turned out that both patients included
in the study had frequently used UV
nail lamps to dry their nail polish.
CAN DRINKING BEER INCREASE
RISK OF PSORIASIS IN WOMEN?
Data published in the Archives of
Dermatology suggest women who
drink regular beer might be at a higher
risk of developing psoriasis, reports the
Los Angeles Times (Aug. 16, 2010).
Investigators looked at drinking habits
among 83,000 women aged 27 to 44
who were part of the Nurses’ Health
Study II. From that group, they analysed
1,069 cases of psoriasis that occurred in
a 14-year follow-up period. Findings
revealed that women who had an aver-
age of 2.3 drinks or more per week had
a 72% greater risk of psoriasis than
women who didn’t drink. When vari-
ous types of alcohol were assessed,
there was a higher risk for the disease
among women who drank regular
beer. The potential reason for the
increase in risk may have to do with
the fact that beer uses starch for fer-
mentation—usually barley. The authors
added that drinking light beer, red and
white wine, or liquor was not linked
with a risk of psoriasis.
PREVENTING SKIN CANCER
Research presented at the American
Academy of Dermatology’s Summer
Meeting 2010 in Chicago suggests that
oral and topical agents might potential-
ly help provide enhanced sun protec-
tion and aid in the prevention of UV-
induced skin cancer, reports The
Times of India (Aug. 6, 2010).
At the meeting, Dr. Craig A. Elmets,
of the University of Alabama at
Birmingham indicated that while each
agent studied works differently, they
have seen encouraging results with
both oral and topical agents, including
non-steroidal anti-inflammatory drugs
(NSAIDs), eflornithine, and certain nat-
ural antioxidants. He cautioned that
evidence to support these benefits is
largely based on animal studies. but
added that NSAIDs have been shown to
be an effective chemo preventive agent
when used in patients with basal cell
nevous syndrome. Eflornithine is anoth-
er therapy that has been shown to have
beneficial effects in preventing basal
cell carcinoma.
INJECTION OF CERTAIN GENE
MIGHT SLOW MELANOMA GROWTH
Researchers from Queen’s University in
Kingston, Ont. have discovered that
injecting the MicroRNA 193b gene into
melanoma cells can slow the growth of
melanoma, reports the Toronto Sun
(Aug. 16, 2010).
This gene was first discovered less
than 10 years ago, and has been found
to slow down cancer cell growth and
decrease levels of the protein cyclin D1
in the tumors. Too much cyclin pro-
motes cancer cell growth, according to
Dr. Victor Tron, head of pathology and
molecular medicine at Queen’s.
He concludes that they are still in
the early days of research, and they
haven’t yet tested it on lab animals. The
next step is to determine safety of the
regimen and determine if it can be
used in clinical trials.
21683B_Skin_Allergy_Pg_:ps 10/18/2010 10:16 PM Page 31

EFFACLAR DUO
With La Roche-Posay thermal spring water

Efficacy against both retentional

and inflammatory lesions,
in a single treatment.

A complete formula
Unclogged pores
A=6™HVa^Xna^X6X^Y ÆKeratolytic
Targeted Linoleic Acid ÆKerato-regulating
Reduced inflammation
Niacinamide ÆAnti-inflammatory
Piroctone Olamine ÆAnti-bacterial, Anti-fungal
Matified, non-greasy effect
Zinc PCA ÆHZWd"gZ\jaVi^c\   

Indications
1 application in the morning and/or evening
ÆAs a monotherapy
ÆCombined with medical treatments
ÆAs a follow-up to treatments

Physiological pH 5.8 68I>K:>C<G:9>:CIH/6FJ6™<AN8:G>C™8N8AD=:M6H>ADM6C:™=N9GD<:C6I:9EDAN>HD7JI:C:™C>68>C-

Alcohol-free 6B>9:™>HDEGDENAA6JGDNAH6G8DH>C6I:™6BBDC>JBEDAN68GNA9>B:I=NAI6JG6B>9:™H>A>86™B:I=NA
B:I=68GNA6I:8GDHHEDANB:G™HD9>JB=N9GDM>9:™H6A>8NA>868>9™CNADC"&'™O>C8E86™A>CDA:>868>9™
Paraben-free
E:CI6:GNI=G>INAI:IG6"9>"I"7JINA=N9GDMN=N9GD8>CC6B6I:™86EGNADNA<AN8>C:™86EGNADNAH6A>-
Oil-free 8NA>868>9™86EGNANA<AN8DA™E>GD8IDC:DA6B>C:™BNG>HINABNG>HI6I:™EDI6HH>JB8:INAE=DHE=6I:
Non-comedogenic ™<AN8:GNAHI:6G6I:H:™;G6<G6C8:
21683B_Skin_Allergy_Pg_:ps 10/20/2010 10:19 PM Page 32

THE # 1 TOPICAL ACNE THERAPY DISPENSED IN CANADA1

• Demonstrated significant global improvement –

fast results within 2 weeks2†
• Excellent tolerability profile3

CLINDOXYL Gel (clindamycin phosphate and benzoyl peroxide) is indicated in the topical treatment of moderate acne vulgaris characterized by the
presence of comedones, papules and pustules. CLINDOXYL Gel is not indicated for the treatment of cystic acne.
For external use only. Avoid contact with eyes and mucous membranes. If significant diarrhea occurs, the drug should be discontinued. CLINDOXYL
Gel should not be given to pregnant or lactating women. Safety and effectiveness in children under 12 have not been established. Use with caution
in patients taking neuromuscular blocking agents. Most common side effects are peeling 16.3%, erythema 7.6%, dryness 7.0%, burning 2.3% and
pruritus 1.7%.
† p<0.01 vs. placebo and p<0.02 vs. clindamycin gel. Global evaluation graded by means of a scale of 0 to 4: 0 = worsening,1 = poor, 2 = fair, 3 = good and 4 = excellent. Based on combined
data from 2 double-blind, randomized, parallel, vehicle-controlled trials lasting 11 weeks. Once-daily application. n = 95 (CLINDOXYL Gel), 89 (clindamycin gel) and 58 (placebo).
1. IMS Health Canada: Canadian CompuScript Audit, April 2010. 2. Lookingbill DP et al. J Am Acad Dermatol 1997;37:590-595. 3. CLINDOXYL Gel Product Monograph, Stiefel Canada Inc.
® Registered trade-mark
Protected by patent CA2142530
STIEFEL CANADA INC.
Montreal, Quebec H4R 1E1
©2009
6HHSUHVFULELQJVXPPDU\RQSDJH
SCI/D/09-08/CDXL/1187/JA-E