Adapalene with benzoyl peroxide (Epiduo) 1 Adapalene with benzoyl peroxide (Epiduo)

Adapalene with benzoyl peroxide (Epiduo)
NPS RADAr | April 2011
1
Adapalene with benzoyl peroxide
(Epiduo)
for severe acne vulgaris
(a-DAP-a-leen with benz-OIL per-OX-ide)
PBS-listed
topical retinoid
Key points
A topical fixed-dose combination gel for severe acne
The gel contains adapalene 0.1% (a retinoid) and benzoyl peroxide 2.5% (an antimicrobial).
Use in combination with an oral antibiotic when starting acute treatment
Adding adapalene with benzoyl peroxide (adapalene–BPO) to doxycycline significantly
improved the treatment success rate at 12 weeks.
Pregnant women, women planning a pregnancy, and women using inadequate
contraception, should not use adapalene–BPO
As with other topical retinoids, there is a potential risk of adverse effects to the foetus.
Dry skin, burning sensation and contact dermatitis are common
Simple dosing strategies may help to reduce skin irritation.
Treated skin is prone to sunburn
Use a non-comedogenic SPF 30+ broad spectrum sunscreen on treated skin.
PBS listing
Restricted benefit
For acute and maintenance treatment of severe
acne vulgaris.4 Acute treatment is in combination
with an oral antibiotic.
May be prescribed by nurse practitioners
(continuing therapy only)
Authorised nurse practitioners may prescribe
continuing therapy of this medicine after it has been
initiated by a medical practitioner. See the PBS
website for more information on nurse practitioner
PBS prescribing.
Additional
information
www.pbs.gov.au/info/
healthpro/explanatorynotes/section1/nursepractitioner
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Adapalene with benzoyl peroxide (Epiduo)
NPS RADAr | April 2011
2
What is it?
Epiduo is a topical fixed-dose combination gel containing
adapalene (0.1%) and benzoyl peroxide (2.5%).
Adapalene is a topical retinoid. It reduces comedone
formation and inflammation.3 Benzoyl peroxide is an
oxidising agent with antimicrobial activity against
Propionibacterium acnes.
Who is it for?
‡
dapalene–BPO is not
A
approved by the TGA for
initiating acne therapy. 3
Consider prescribing adapalene–BPO for severe
acne when a patient has failed to respond, or has
not tolerated, a first-line treatment option‡, e.g.
an over-the-counter product containing benzoyl
peroxide. Acute treatment must be in combination
with an oral antibiotic e.g. doxycycline. In clinical
trials, acute treatment was for 12 weeks.
Adapalene–BPO can be continued as maintenance
therapy without an oral antibiotic (see Benefits
are maintained for 6 months with continued
adapalene–BPO therapy).
There are no data from children less than 12 years
of age.3 As with other topical retinoids, adapalene–
BPO should be avoided in pregnant women, women
planning a pregnancy, and women using inadequate
contraception.5–7
Where does it fit?
Adapalene–BPO is a PBS-listed alternative to
topical tretinoin; it is an option for both acute
and maintenance treatment of severe acne.
Table 1.
Median reduction (%)
in lesion count from
baseline to week 12
Additional
information
Refer to this review at
www.nps.org.au for
details
Adapalene–BPO
plus doxycycline
(n = 232)
Doxycycline
(n = 227)
Total lesion
count*
64†
41
Inflammatory
lesion count
72†
48
Noninflammatory
lesion count
61†
40
*Sum of inflammatory and non-inflammatory lesions.
Inflammatory lesions are papules, pustules and
nodules/nodulocystic lesions; non-inflammatory
lesions are open or closed comedones
†Statistically significant improvement over doxycycline
monotherapy (p < 0.001)
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Australian guidelines currently recommend a topical
retinoid (e.g. ≤ 0.05% tretinoin cream available by
private prescription) or benzoyl peroxide (5%) in
combination with an oral antibiotic for moderate
acne.8 A combined oral contraceptive may be used
instead of, or in addition to, the topical preparation
in female patients.5,8 For moderate to severe acne,
tretinoin 0.05% or 0.1% cream is recommended
in combination with an oral antibiotic.8
If there is scarring, a family history of scarring,
or acne is refractory to topical adapalene–BPO,
the patient should be referred to a dermatologist
for consideration of further treatment, including
oral isotretinoin.8 Avoid adapalene–BPO, and other
topical anti-acne preparations, in patients receiving
oral isotretinoin therapy because of the increased
risk of cutaneous adverse effects.5
How does it compare?
Adapalene–BPO, combined with oral doxycycline,
has been compared with doxycycline monotherapy
in the acute treatment of patients with severe
acne vulgaris.1 There are no head-to-head trials
comparing the effect of adapalene–BPO with
that of other topical or systemic retinoids. Oral
isotretinoin is preferred for severe cystic acne,
when response to therapy is inadequate or there
is a risk of scarring (see Where does it fit?).8
Both components of adapalene–BPO contribute
to its efficacy.9–11
Acute treatment with adapalene–BPO
and doxycycline reduces acne severity
In patients with severe facial acne vulgaris
(≥ 12 years of age; n = 459), the treatment
success rate§ at 12 weeks was higher with
adapalene–BPO (applied once daily at night)
and 100 mg oral doxycycline, than with
doxycycline monotherapy (31.5% vs 8.4%,
respectively; p < 0.001).1 Adapalene–BPO
and doxycycline reduced comedone, papule
and pustule count (total lesion count), the
primary efficacy end point, by 23% compared
with doxycycline alone (Table 1).1
Defined as the percentage of patients rated ‘clear’ or
‘almost clear’ on the Investigator’s Global Assessment scale
of acne severity.
§
Adapalene with benzoyl peroxide (Epiduo)
NPS RADAr | April 2011
3
Evidence snapshot
What is known about
this drug
In a randomised controlled
trial, adapalene–BPO with oral
doxycycline reduced acne severity
rating in more patients than
doxycycline alone (31.5% vs.
8.4%, respectively; p < 0.001).1
Improvements in total lesion count
were maintained for 24 weeks
after stopping doxycycline by
79% of patients who continued
using adapalene–BPO.2
Areas of uncertainty
What does NPS say?
It is unclear whether acne will
recur after stopping adapalene–
BPO; no clinical trial has included
a post-treatment follow-up.
Adapalene with benzoyl
peroxide is a PBS-listed option
for treating severe acne when
a topical retinoid is indicated.
Physical, psychological and/or
social factors may contribute
to the diagnosis.
The effect of adapalene–BPO
on severe acne vulgaris has not
been compared with that of
other topical retinoids.
Common adverse effects include
skin irritation and dryness.1,3
Benefits are maintained for 6 months
with continued adapalene–BPO therapy
Patients who responded to adapalene–BPO with
doxycycline or doxycycline alone (n = 243; acne
rated ‘moderate’ or better on the Investigators
Global Assessment scale of acne severity) were
eligible to enter a maintenance phase.1,2
*M
aintenance success
was defined as the
percentage of subjects
maintaining at least
50% of the improvement
obtained with prior
combination therapy
(adapalene–BPO
with doxycycline
100 mg or vehicle
gel with doxycycline
100 mg), in terms of
total lesion count.
Participants were randomly assigned to adapalene–
BPO or gel vehicle (placebo); neither group received
oral doxycycline. After 24 weeks, 79% of patients
treated with adapalene–BPO maintained their
improved total lesion count* compared with
46% who received placebo.
Safety issues
The common adverse effects of adapalene–BPO —
dry skin, burning sensation and contact dermatitis —
are characteristic of topical acne therapies; sunburn
and pruritus were uncommon.3 All occurred at the
site of application, and the majority were rated as
being of mild or moderate severity in clinical trials.1,3,13
Stinging and burning was most severe after 2 weeks
of treatment with adapalene–BPO and doxycycline,
and decreased thereafter.1
Of the 459 patients enrolled in the 12 week
acute treatment trial, six withdrew because of
adverse events; two receiving adapalene–BPO
and doxycycline, and four doxycycline alone
(see Antibiotic-related nausea, vomiting and
diarrhoea may occur during acute treatment).1
Report suspected adverse reactions to the
Therapeutic Goods Administration (TGA) online
(www.ebs.tga.gov.au) or by using the ‘Blue Card’
distributed three times a year with Australian
Prescriber. For information about reporting adverse
reactions, see the TGA website (www.tga.gov.au).
Antibiotic-related nausea, vomiting and
diarrhoea may occur during acute treatment
In the 12 week trial comparing adapalene–BPO
and doxycycline with doxycycline alone, 9.6%
of patients (n = 44) experienced gastrointestinal
disorders.1 Three participants discontinued
because of these effects.
Tetracyclines, including doxycycline, may also
induce phototosensitivity and patients should
be advised about protective measures (see
Information for patients).6
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Adapalene with benzoyl peroxide (Epiduo)
NPS RADAr | April 2011
4
Avoid in pregnancy and women using
inadequate contraception
Adapalene is a Category D drug under the Australian
(formerly ADEC) pregnancy categorisation. It should
not be used during pregnancy because of the
potential risk of adverse effects to the foetus.5,8
Clinical trials of adapalene–BPO excluded women
planning a pregnancy.1,9,10,13 As with other topical
retinoids, adapalene should be avoided in women
planning to conceive or who are not taking
adequate contraceptive precautions.5–7
Reason for PBS listing
The Pharmaceutical Benefits Advisory
Committee (PBAC) recommended a restricted
benefit listing for adapalene–BPO for acute
(in combination with an oral antibiotic) and
maintenance treatment of severe acne on
the basis of acceptable cost-effectiveness
compared with placebo.4
* It may be possible to
apply topical retinoids
less frequently if
maintenance therapy
response is adequate. 5,15
Dosing issues
Adapalene–BPO should be applied once daily,*
at night, after washing with a soap-free cleanser.
The skin should be allowed to dry before applying
a thin film of gel over the entire acne affected area,
taking care to avoid the eyes, lips, cuts, scrapes
and sunburnt skin.5,14
Simple dosing strategies may help
to reduce skin irritation
Although irritation may improve with time, it can limit
topical retinoid use.15 To help minimise skin irritation
and dryness consider advising patients to:3,5,15,16
remove residual adapalene–BPO by washing
the treated skin with a soap-free cleanser
in the morning
use adapalene–BPO less frequently
e.g. on alternate days
apply adapalene–BPO for a short period
of time e.g. 15–20 minutes, and then wash
from the skin
use a non-comedogenic moisturiser.
Note that some patients may need to stop using
adapalene–BPO because of skin irritation.3
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Information for patients
Provide patients and carers with the
following information.3,5,8,15
Adapalene–BPO should not be used
by pregnant women, women planning
a pregnancy and women using inadeqate
contraception, because there is a potential
risk of birth defects.
Apply a thin film of gel over the entire
acne-affected area at night. This will
help to prevent acne formation, as well
as treat existing acne.
Skin irritation and/or an apparent
worsening of acne may occur during
the first few weeks of treatment (see
Simple dosing strategies may help to
reduce skin irritation).
Adapalene–BPO can make skin
more prone to sunburn. Avoid excess
sunlight and protect treated skin with
a non-comedogenic, SPF 30+ broad
spectrum sunscreen.
The full benefit of treatment may not
be apparent for several months, so
patience is required.
The antibiotic used during acute
treatment may cause gastrointestinal
symptoms. It may also increase the
risk of photosensitivity.
Benzoyl peroxide can bleach or
discolour hair, clothes and bed linen.
Do not wash affected skin more than
twice a day and use a low-irritant,
pH-balanced, soap-free cleanser.
Picking or squeezing lesions can make
acne worse and increase the risk of
permanent scarring. Avoid vigorous
scrubbing of affected skin, and using
astringent or exfoliating agents.
Discuss the Epiduo consumer medicine
information (CMI) leaflet with the patient.
Adapalene with benzoyl peroxide (Epiduo)
NPS RADAr | April 2011
5
Benzoyl peroxide is present in many topical
preparations
and providing reassurance may be of benefit to some
patients.
Ensure patients and their carers are aware that
Epiduo contains two active ingredients.
Counsel patients that:15,17
Advise patients to stop using over-the-counter
products containing benzoyl peroxide and/or
previously prescribed adapalene (or other topical
retinoid), and to return unwanted medicines to
their pharmacist for safe disposal.14
Counsel patients about the condition
and its course
Acne may have a significant social and emotional
impact upon the individual.6,8,15 Addressing concerns
acne is very common among young
people, but it will improve with time
it is not caused by poor hygiene, and
excessive washing can make acne worse
no direct link has been found between
diet and acne
acne is not infectious
UV light has little benefit in acne. Use appropriate
sun protection measures when outside.
References
1.
Gold LS, et al. Cutis 2010;85:94–104.
8.
Therapeutic Guidelines: Dermatology. Version 3.
2.
Adapalene-benzoyl peroxide (BPO) gel in the
treatment of acne vulgaris as a 6-month maintenance
(ACCESS II). ClinicalTrialsgov 2008. http://
clinicaltrials.gov/ct2/show/NCT00687908?term=ada
palene&rank=10 (accessed 15 December 2010).
9.
Thiboutot DM, et al. J Am Acad Dermatol
2007;57:791–9.
3.
Galderma Australia Pty Ltd. Epiduo product
information. 4 June 2010.
4.
Pharmaceutical Benefits Branch. Adapalene with
benzoyl peroxide, gel, 1mg–25mg per g (0.1%–2.5%),
30 g, Epiduo, November 2010. Canberra: Australian
Government Department of Health and Ageing, 2010.
http//www.health.gov.au/internet/main/publishing.
nsf/Content/public-summary-documents-by-meeting.
(accessed 10 March 2011).
12. US Food and Drug Administration Guidance
for Industry. Acne vulgaris: developing drugs
for treatment. 2005. http://www.fda.gov/
downloads/Drugs/GuidanceComplianceRegulatory
lnformation/Guidanc-es/UCM071292.pdf
(accessed 4 January 2011).
5.
Australian Medicines Handbook 2010.
6.
Cook D, et al. Aust Fam Physician;39:656–60.
7.
Purdy S, Deberker D. Acne vulgaris, Clin Evid (Online)
2008; May 15;2008. pii: 1714. http://www.ncbi.nlm.
nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMe
d&dopt=Citation&list_uids=19450306.
10. Gollnick HP, et al. Br J Dermatol 2009;161:1180–9.
11.
Gold LS, et al. Cutis 2009;84:110–6.
13. Pariser DM, et al. J Drugs Dermatol 2007;6:899–905.
14. Galderma Australia Pty Ltd. Epiduo consumer
medicine information; 25 February 2009.
15.
National Health Service Clinical Knowledge Summaries.
Acne vulgaris. 2009. http://www.cks.nhs.uk/home
(accessed 17 December 2010).
16. Goodman G. Aust Fam Physician 2006;35:705–9.
17.
Goodman G. Aust Fam Physician 2006;35:613–6.
Date published: April 2011
The information contained in NPS RADAR is derived from a critical analysis of a wide range of authoritative evidence
and is current at the time of publication. Any treatment decisions based on the information provided in NPS RADAR
should be made in the context of the clinical circumstances of each patient.
NPS RADAR articles may be updated when there is new evidence about safety or efficacy, or in case of regulatory
or PBS listing changes.
Please refer to www.npsradar.org.au for the most recent version as well as any supplementary information.
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