COLD SORES AND AVAILABLE TREATMENTS your reference guide to

your reference guide to
The Condition
COLD SORES
AND AVAILABLE
TREATMENTS
Cold Sore Cycle
Treatment Options
Counselling Tips
Clinical Data
View References
The Condition
COLD SORES:
A common, bothersome condition
Warnings and precautions
Help reduce the transmission of HSV-1
90
%
20 -40
%
1/2
Counsel patients that the cold sore virus is contagious — don’t wait to treat:
• Primary infection occurs through direct mucosal contact with the virus from a
lesion or contaminated body fluid (e.g., saliva)
• Up to 90% of the population
are infected with the cold
sore virus (HSV-1)
1
• 20 to 40% of the population
exposed to the cold sore
virus experience recurrent
infections
2
Cold Sore Cycle
5
• The population at highest risk of being infected by the HSV-1 virus is children
under the age of 10, followed by adolescents and young adults
• Approximately one-half of
cold sore sufferers classify
outbreaks as moderate to
severe and bothersome*
5
3
Common cold sore triggers
Knowing the common cold sore triggers may help your patients identify their own
personal triggers and thereby take the necessary steps to manage them.
Initial infection with herpes simplex virus 1 (HSV-1)
4,5
• The virus may reactivate after the initial
infection causing either:
• No symptoms (asymptomatic viral shedding)
• Symptoms but no cold sore (aborted cold sore)
• Symptoms that develop into a classic cold sore
Treatment Options
• Occurs early in life
• I s obtained from an infected person;
however, the initial infection does not
present as a cold sore
• Once the infection runs its course, the virus
remains in the body in a dormant state,
usually in the large facial nerve ganglion
Common cold sore triggers
4–7
• Fever
• Illness
INTERNAL
TRIGGERS
(UNPREVENTABLE)
• Menstruation
• Presence of a second virus (flu, cold)
• Fatigue
Counselling Tips
• Factors that depress the immune system
Viral entry
(HIV infection, cancer therapy)
Sensory
neurons
• Windburn
EXTERNAL
TRIGGERS
Trigeminal
ganglion
(PREVENTABLE)
• Ultraviolet radiation (sunlight)
• Excitement
†
• Emotional stress
†
• Dry lips
• Physical injury
4
• Dental treatment
†
Clinical Data
Adapted from GSK data on file, 2010.
May not be preventable
Findings were obtained from 500 online interviews completed in February 2011 of consumers 18–59 years of age. All had experienced at least one cold sore in the past 12 months.
*
3
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2
The cold sore virus is for life. Give your patients real pharmacological guidance.
The cold sore virus is for life. Give your patients real pharmacological guidance.
3
The Condition
Cold sore duration
Cold sore phases
Duration and severity of a cold sore (herpes labialis)
Phase 2:
Macule/Erythema
Phase 1:
Tingle/Prodrome
• Untreated cold sores can last up to 10 days
‡7
5
1
1,5
1
9
• Cold sores can no longer abort once they reach the blister stage
5
9
• First visible sign of oncoming lesion is redness
in the area where prodrome symptoms
were noticed
• Skin is not elevated or raised above the
surrounding skin
• This phase lasts for a few hours
1,9
Cold Sore Cycle
• A recurrent cold sore is often preceded by
distinctive symptoms:
- Pain, burning, itching, tingling
- Infected area may feel numb or very sensitive
- Noticed in area where cold sores develop
- Skin appears normal
• ~60% of cold sore sufferers experience prodrome
• Symptoms occur as viral particles travel down
trigeminal ganglion nerve to the skin
• Prodrome phase lasts from a few hours to 1 day
• Ranges of severity:
− - aborted lesions that do not progress beyond an initial prodrome
− - lesions with vesicle, ulcer and crusting stages
− - large, extensive lesions
9
1
5
1
Blisters Form
and Grow into Pustules
1
Blisters Break Down
to Form an Ulcer
Viral
Phase
Phase 3:
Papule
Wound Phase
Phase 4:
Blister
• The red area swells and small, painful red
lumps appear (papule)
• May see red skin discoloration (may extend
beyond bump or lump)
• As lesion progresses, small papules close to
one another start to join together over a period
of a few hours and become painful
• May progress to a classical lesion, or cold sore
may heal (abort)
1
Scab Falls Off
Scabbing
9
Dry Flaking
and Residual
Swelling
Tingle (Prodrome)/
Macule (Erythema)/
Papule
-1
0
1
2
3
4
6
8
1
10
• As cells are killed, papules enlarge to form a
crop of tiny, painful, fluid-filled blisters
(vesicles)
• Blisters appear during the second to third day
of cold sore development
• Blisters are 2–5 mm in diameter
• Cold sore will no longer abort
Treatment Options
Relative Clinical Severity
Crusting
1
1
1
9
9
Virus Reactivates
Time (days)
Adapted from Spruance, 1992, and data on file.
8
1
Phase 5:
Pustule
• White blood cells enter area to help fight
the infection
• Vesicles fill with pus (pustule)
• Pustule fluid is highly contagious
• Cold sore remains painful
1
When a patient has a cold sore, they should be aware that they are infectious
until the cold sore has healed and cautioned to avoid contaminating others.
1
1
1
1
Counselling Tips
Period of infectivity
Phase 6:
Ulcer
• Vesicles and pustules eventually burst and join
together to form one large, shallow, painful,
weeping sore
• Cold sore has a grey appearance surrounded by
a bright red ring of inflammation
• Fluid contains a large amount of virus
• Glands in neck may become swollen
1
1
1
1
Phase 8:
Scabbing
Phase 7:
Crusting
1
• Crusts completely dry out to form a scab
• Pain is less intense and may become very itchy
• As scab dries, it shrinks to form painful cracks
that may bleed
• First scab may come off and a second or third
(smaller) scab may form
1
Clinical Data
• The slough in the centre of the ulcer dries
out to form a golden-yellow crust
1
1
‡
In a combined analysis of two clinic-initiated, double-blind, placebo-controlled, multicentre trials, the mean historical cold sore duration
reported by the subjects receiving abreva was 9.5 (±4.2) days (n=370).
7
9
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4
The cold sore virus is for life. Give your patients real pharmacological guidance.
The cold sore virus is for life. Give your patients real pharmacological guidance.
5
The Condition
Treatment goals
Treatment categories
As a valued health care professional, the education you provide to patients is
instrumental in helping them to make smarter choices between medicine and myth. Help
them choose a treatment that is formulated to effectively meet their treatment goals.
Prescription
Treatments
Non-Prescription Treatments
Viral Entry
Blocking Agent
MOA Unclear
Home
Remedies
Medical
Device
Antivirals
Cold Sore Cycle
Products that
Provide Temporary
Symptomatic
Treatment
MOA
Disrupts viral
replication by
inhibiting viral
DNA penetration
into healthy lip
cells.
10
Zinc sulfate/
heparin
sodium:
Precise
mechanism
of action is
unclear.
11
Primarily
moisturizers and
local anesthetics
that provide
temporary relief
and have not been
shown to shorten
healing time.
Unknown
MOA
Hydrocolloid
patch
12
11
3% propolis
ACF: Precise
mechanism
of action is
unclear.
1
Shortened
symptom
duration
Symptom
relief
Treatment that helps
prevent the virus
from entering cells
and inhibits the
virus from infecting
healthy skin cells
Treatment Options
Abreva
(topical
n-docosanol
cream)
®
Lipactin
(zinc sulfate/
heparin
sodium)
®
ColdSore-FX™
(3% propolis
ACF)
Local anesthetics
Antiseptics/
disinfectants
Camphor
Phenol
Menthol
L-lysine
Moisture barriers
Sunscreen
Zinc oxide
Tannic acid
Mouthwash
Alcohol
Tea tree oil
Yogurt
Dietary
supplements
Polysporin
Cold Sore
Healing
Patch
®
Counselling Tips
Shortened
healing time
13–15
Treatment Options
Recommend a treatment and provide counselling based on:
Disrupt viral
replication by
inhibiting viral
polymerase in lip
cells where viral
penetration has
occurred, thus
speeding the
healing process.
Zovirax
(topical acyclovir)
Zovirax
(oral acyclovir)
Valtrex
(oral valacyclovir)
Famvir
(oral famciclovir)
®
®
®
®
NOTE: Advise patients to always talk to a health care professional before using any treatment.
Clinical Data
Product examples are not an exhaustive list.
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6
The cold sore virus is for life. Give your patients real pharmacological guidance.
The cold sore virus is for life. Give your patients real pharmacological guidance.
7
Profile of the cold sore sufferer
There is no cure for the cold sore virus. For those patients who suffer from cold sores,
they will recur throughout their life. However, proper treatment can minimize the
duration of outbreaks.
The majority of sufferers intensely dislike cold sores, primarily their appearance and the time
they take to disappear. They look to you for guidance on how to effectively speed the healing.
16
Counselling Tip 1
®
9,16,17
1
Counselling Tip 3
Help your patients understand
the difference between medicine
and home remedies. Sometimes
patients believe that their home
remedy has been effective, when in
reality their cold sore may have naturally aborted
as a result of an effective immune response.
1
Counsel your patients that effective medical
treatment options are available to treat cold sores.
Quick cold sore reference
• Up to 90% of the population are infected with the cold sore virus (HSV-1).
1
Cold Sore Cycle
If a patient presents at the blister
stage, remind them that when
dealing with the cold sore virus,
all treatments are most effective
when used early in the course of
a cold sore. When recommending abreva , begin
treatment as soon as possible and continue
application through all phases of the cold sore
cycle until it heals. Remind them that for best
results begin treatment early.
The Condition
Help your patients understand the cold sore virus
•Untreated cold sores can last up to 10 days.
‡7
•Treatment goals should be geared to meet each patient’s specific needs, such as shortened
healing time.
•Advise patients that to be most effective, treatments should be started as soon as possible
when they feel or see the first signs of a cold sore outbreak.
16,17
•Treatment should be continued according to label directions. For abreva , that is to continue
treatment until the cold sore is healed.
®
10
Counselling Tip 2
Instruct your patients on how to
prevent the virus from spreading
to healthy cells:
• Set realistic treatment goals.
Minimizing the duration of a cold sore
through effective treatment is possible.
7,16
16,17
• Continue treatment until the cold sore is healed.
• Remind patients that they are contagious
throughout the cold sore cycle and should
avoid any close physical contact with others.
For many sufferers, stress is a
key cold sore trigger. Cold sores
often occur just before events
such as weddings, back to school,
new relationships, etc. Counsel
your patients to recognize what their triggers are
so they can take appropriate precautions, and
advise them to prepare for any future outbreaks.
Counselling Tip 5
Counselling Tips
• A
dvise them to begin treatment as soon as
possible when they feel or see the first signs of
a cold sore outbreak.
Treatment Options
Counselling Tip 4
Know the treatment categories.
This will help you provide the
most effective treatment option
to your patients and will help
manage their expectations on
healing time.
Clinical Data
In a combined analysis of two clinic-initiated, double-blind, placebo-controlled, multicentre trials, the mean historical cold sore duration
reported by the subjects receiving abreva was 9.5 (±4.2) days (n=370).
‡
7
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8
The cold sore virus is for life. Give your patients real pharmacological guidance.
The cold sore virus is for life. Give your patients real pharmacological guidance.
9
§//
Year
published
Treatment
Penciclovir
Number of
subjects
Cold sore
duration
(days)
782
4.8 m
#
Clin
Placebo
791
5.5 m
Docosanol
370
4.1 m
Clin
Placebo
367
4.8 m
Acyclovir
(Study 1)
334
4.3 a
Propolis
18
0.008
Number of
subjects
Cold sore
duration
(days)
33
6.2 a
††
2001
Sacks
2001
2008
Placebo
35
9.8 a
Hydrocolloid
patch
179
7.57 a
Placebo
End-point
assessment
p value
Reference
Sub
§§
<0.00001
Hoheisel
2001
////
0.37
Karlsmark
2008
‡‡
22
23
Sub
172
##
7.03 a
Note: No published studies were identified for Lipactin Gel (heparin sodium, zinc sulfate).
®
Spruance
2002
19
Clin
Placebo
352
4.8 a
Acyclovir
(Study 2)
348
4.6 a
0.007
a = mean value based on ANOVA.
Sub = the primary end point was assessed by the subject in both studies.
Propolis study used subject-assessed cold sore healing as the primary end point. Patients were seen in clinic twice
during the entire study: at start of treatment and after the patient reported that their lesion had healed.
Patch study used time to healing as the end-point of the trial; however, the subject’s global assessment of
therapy was the primary end point for analysis. A secondary end point was clinician-assessed time to
complete healing of the cold sore.
Study design: non-inferiority study.
††
‡‡
§§
//// Spruance
2002
19
Clin
Placebo
351
5.2 a
Penciclovir
1516
4.6 m
Placebo
1541
5.4 m
Acyclovir +
hydrocortisone
601
5.7 a
Acyclovir
610
5.9 a
Placebo
232
6.5 a
0.006
Clin
0.0001
Clin
<0.01
(acv + hcz
vs. Pbo)
Raborn
2002
##
20
Counselling Tips
2002
2011
Spruance
1997
Treatment
Treatment Options
2002
<0.001
Year
published
Reference
7
2001
2002
p value
Cold Sore Cycle
1997
End-point
assessment**
The Condition
Cold sore studies for other (non DIN)
cold sore products
Cold sore studies reporting time to healing
for topical products
Hull
2011
21
Clinical Data
All studies had similar primary end point: first dose of treatment to healed cold sore.
All studies used clinician-assessed cold sore healing as the primary end point
m = median value based on Kaplan-Meier survival analysis. a = mean value based on ANOVA.
** Clin = Healing was assessed during clinic visit by a trained clinician.
§
//
#
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10
The cold sore virus is for life. Give your patients real pharmacological guidance.
The cold sore virus is for life. Give your patients real pharmacological guidance.
11
Cold sore duration: Untreated vs. treated
Cold sores are self-limiting and will resolve on their own. However, published literature has shown
that an untreated cold sore can last between 6 to 10 days. Healing times of selected products also
vary and should be taken into consideration when recommending a cold sore treatment.
16
abreva®§§§7
Zovirax
ColdSore-FX
median 4.1
®‡‡‡19
mean 4.3
™†††22
median 6.2
Polysporin® Cold Sore
Healing Patch***23
mean 7.57
Untreated cold sore16
range 6 to 10
0
2
4
6
8
10
12
Cold Sore Healing Time (Days)
For more detailed information refer to pages 10 and 11.
Patient reminder
Effective cold sore
treatments can:
Speed
the healing
Minimize
symptom duration
Begin treating a cold sore at the first sign of symptoms (tingle stage)
treatment until the cold sore is healed.
16,17
Multicentre, randomized, assessor-blinded study.
179 subjects applied Compeed cold sore patch and
172 subjects applied acyclovir cream 5% at the onset
of symptoms until the lesion healed, for a maximum of
10 days. The primary end point was the subject’s global
assessment of therapy.
Randomized, double-blind, placebo-controlled, parallel,
patient-assessed study in which patients applied either
propolis (n=33) or placebo (n=35) 5 times daily and
recorded assessments in a diary until cold sore was
healed (up to 12 days). Patients were seen in clinic 2 times
during the study—at start of treatment and after the
patient reported that their lesion had healed.
Randomized, double-blind, vehicle-controlled,
multicentre trial (n=686). Patients with clinical histories
of recurrent herpes labialis received either acyclovir
(n=334) or vehicle (n=352) and initiated therapy within
1 hour of prodromal or erythema stage. Treatment was
applied 5 times daily for 4 days. Patients were followed
daily at the clinic until healing occurred.
Two identical randomized, double-blind, placebocontrolled, multicentre studies (n=737). Patients with
documented histories of herpes simplex labialis received
either docosanol or polyethylene glycol placebo and
initiated therapy in the prodrome or erythema stage of an
episode. Treatment was administered 5 times daily until
healing occurred (i.e., the crust fell off spontaneously or
there was no longer evidence of an active lesion) with
twice-daily visits.
1. Data on file. © SmithKline Beecham, UK, 1992.
2. Data on file. © SmithKline Beecham, UK, 1995.
3. Data on file. © GSK 2011.
4. Data on file. © GSK 2010
5. Treister NS, Woo S-B. Topical n-docosanol for
management of recurrent herpes labialis.
Expert Opin Pharmacother 2010;11(5):353–860.
***
®
23
†††
22
‡‡‡
19
§§§
7
6. GlaxoSmithKline. Common triggers that can lead to a
cold sore outbreak. Accessed at: http://www.abreva.
ca/ColdSoreBasics/triggers.aspx on April 7, 2011.
7. Sacks SL, Thisted RA, Jones TM, et al. Clinical
efficacy of topical docosanol 10% cream for herpes
simplex labialis: a multicenter, randomized,
placebo-controlled trial. J Am Acad Dermatol
2001;45:222–230.
8. Spruance SL. Semin Dermatol 1992;11:200.
9. Data on file. © GSK 2010.
10. Abreva (docosanol cream, 10%) Product
Monograph. GSK Consumer Healthcare Inc. July
23, 2008.
11. Data on file. © GSK 2009.
12. Johnson & Johnson Inc. Polysporin Cold Sore
Healing Patch. Accessed at: http://polysporin.ca/
en/p-coldsorehealing.asp on September 23, 2011.
13. Zovirax Product Monograph, GlaxoSmithKline.
Accessed from e-CPS July 2011.
14. Valtrex Product Monograph, GlaxoSmithKline.
Accessed from e-CPS July 2011.
15. Famvir Product Monograph, Novartis
Pharmaceuticals. Accessed from e-CPS July 2011.
16. Harmenberg J, Oberg B, Spruance S. Prevention of
ulcerative lesions by episodic treatment of recurrent
herpes labialis: a literature review. z Derm Veneriol
2010;90:122–130.
17. Spruance SL, Jones TM, Blatter MM, Vargas-Cortes
M, Barber J, Hill J, et al. High-dose, short-duration,
early valacyclovir therapy for episodic treatment of
cold sores: results of two randomized, placebocontrolled, multicenter studies. Antimicrob Agents
Chemother 2003;47(3):1072–1080.
18. Spruance SL, Rea TL, Thoming C, et al. Penciclovir
cream for the treatment of herpes simplex labialis. A
®
®
®
®
®
and continue
randomized multicenter, double-blind, placebocontrolled trial. Topical penciclovir collaborative
study group. JAMA 1997;277(17):1374–1379.
19. Spruance SL, Nett R, Marbury T, Wolff R, Johnson J,
Spaulding T. Acyclovir cream for treatment of herpes
simplex labialis: results of two randomized, doubleblind, vehicle-controlled, multicenter clinical trials.
Antimicrob Agents Chemother 2002;46(7):2238–2243.
20. Raborn GW, Martel AY, Lassonde M, et al. Effective
treatment of herpes simplex labialis with penciclovir
cream: combined results of two trials. J Am Dent
Assoc 2002;133(3):303–9.
21. Hull CM, Harmenberg J, Arlander E, et al. Early
treatment of cold sores with topical ME-609
decreases the frequency of ulcerative lesions: a
randomized, double-blind, placebo-controlled,
patient-initiated clinical trial. J Am Acad Dermatol
2011;64(4):696.e1–11.
22. Hoheisel O. The effects of Herstat (3% propolis
ointment ACF) application in cold sores: a doubleblind placebo-controlled clinical trial. Journal of
Drug Assessment 2001;4:161–226.
23. Karlsmark T, Goodman JJ, Drouault Y, et al.
Randomized clinical study comparing Compeed
cold sore patch to acyclovir cream 5% in the
treatment of herpes simplex labialis. JEADV
2008;22:1184–1192.
®
All products are trademarks or
registered trademarks of their
respective companies.
©2011 GlaxoSmithKline
10810
The cold sore virus is for life. Give your patients real pharmacological guidance.
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