B A S I C S

BASICS OF COMPOUNDING for

Cold Sores or Fever Blisters

Loyd V. Allen, Jr., PhD, RPh

Introduction
There are eight identied human herpes viruses, including:
herpes simplex virus (HSV) type 1; HSV type 2; varicellazoster virus (type 3); Epstein-Barr (EB)infectious mononucleosis virus (type 4); cytomegalovirus (CMV) (type 5); two
associated with roseola (HHV-6 and HHV-7); and another
linked with Kaposis sarcoma (HHV-8). 1 Herpes viruses 1 and
2 affect, primarily, the oral and genital areas, respectively.
Even though HSV-1 largely involves the mouth and oral cavity, it may be responsible for causing some urogenital infections. HSV-1 infections are usually known as cold sores or
fever blisters. 1
HSV-1 infections are a continuing global public health problem for which the various forms of treatment generally have
minimal impact. 2 Fever blisters and canker sores are two of the
most common oral problems exhibited by patients seeking advice from pharmacists; about 20% of the United States (US)
population experience these lesions every year. 2 More than
85% of adults have serologic evidence of HSV-1 infections,
which have most commonly been acquired during childhood. 1
Generally, both problems are self-limiting, but treatment is
available to minimize pain/discomfort and, in some cases,
shorten the duration of the disorder.
Continuing Education
GOALS AND OBJECTIVES
Basics of Compounding for Cold Sores or Fever Blisters
Goal: The goal of this presentation is to provide compounding
pharmacists with supportive information on the treatment of cold
sores/fever blisters using compounded formulations.
Objectives: After reading and studying the article, the reader will be
able to:
1. List eight human herpes viruses.
2. Describe the symptoms presented by patients with fever blisters.
3. Discuss progress of fever blisters from exposure to eruption.
4. List three primary goals of treatment of fever blisters.
5. List at least ve drugs commonly used to treat fever blisters.
To complete this continuing education program, go to www.ijpc.com. The
program is presented by the IJPC in partnership with P*ceutics Institute @
PCCA, which is accredited by the American Council on Pharmaceutical
Education as a provider of continuing pharmaceutical education. Upon
successful completion of 70 percent of the questions and completion
of the evaluation, an ACPE statement of credit for one (0.1 CEU)
credit will be immediately available for printing. The cost is $15.

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Vol. 8 No. 3 May/June 2004

Symptoms
Cold sores usually begin as small, red papules of uidcontaining vesicles. The lesions may coalesce into larger
lesions and become encrusted. They can be singular or multiple and may be accompanied by no pain, some pain or moderate pain. The duration of the outbreak is normally from 7 to
14 days; scarring is rare. Lesions usually occur at the junction
of the mucous membrane and skin of the lips or nose.

Cause
Cold sores are induced by the herpes simplex virus (HSV-1),
which is contagious and is thought to be transmitted by direct
contact. It is possible that uid from the herpes vesicles contains the live virus and may serve to transmit the virus from
patient to patient. HSV-1 gains entrance through a break in
the skin or even through direct contact with intact mucous
membranes. Potentially, any person who comes into contact
with the virus may become infected. The virus ascends the
sensory nerve axons and establishes chronic, latent infection in
various ganglia, including trigeminal, facial and vagus ganglia.
In addition, it may be possible that a latent infection also develops in tissues such as the epithelium of the lips. Once infected, a patient may have recurrent lesions throughout life.
The dormant virus can remain so for long periods of time and
then can reactivate when the patient is exposed to a trigger.
Triggers of viral reactivation include ultraviolet radiation,
stress, fatigue, chilling and windburn. Additional triggers are:
malnutrition, fever, injury, menstruation, dental work, infectious diseases such as colds and the u, exposure to extreme
cold or heat, and other situations that may depress the
immune system.
A prodrome, an early or premonitory symptom of a disease,
may involve burning, itching, tingling or numbness in the
area, where the lesion will later erupt in about 1236 hours.
Then the lesion becomes visible as small, red papules of uidcontaining vesicles; they may range in size from 1 to 3 mm in
diameter. If they coalesce, they form a larger area comprising
groups of vesicles. If they burst when mature, a coalesced
group may form a crust over the top of the vesicles. If pus is
present, this is indicative of a secondary bacterial infection.
In those instances when the prodrome does not occur, it has
been suggested that this nonclassical lesion is caused by a
dormant virus that is resident in epithelium dendrites. These
viruses have a head start when a trigger occurs, and lesions
may appear within 2436 hours after a trigger. These lesions
respond only to prophylactic therapy, if they respond at all. 2

B A S I C S

Table 1. Drugs Used to Treat Cold Sores.

Drug

Usual Strength

Anesthetics/Antipruritics/Anti-Inflammatories
Benzocaine
Benzyl alcohol
Camphor
Dexamethasone
Dibucaine
Diphenhydramine hydrochloride
Dyclonine hydrochloride
Hydrocortisone
Lidocaine
Menthol
Phenol
Tetracaine
Triamcinolone

5-20%
10-33%
0.1-3%
0.1%
0.25-1%
1%
0.5-1%
0.5-1%
1-5%
0.1-1%
1-3%
2%
0.1%

Antivirals
Acyclovir
Deoxy-D-glucose
Famciclovir
Penciclovir
Valcyclovir
Docosanol
Foscarnet
Sodium lauryl sulfate

5%
0.2%
Oral
1%
Oral
10%
Injection
5%

Herbal
Lemon balm (dried extract)

1%

Emollients
Allantoin
Cocoa butter
Dimethicone
Glycerin
Petrolatum

qs
qs
qs
qs
qs

The classical lesions accompanied by a prodrome, may

arise from dormant virus harbored in the ganglia. When the
trigger occurs, the dormant virus replicates and travels along
peripheral nerves to cause vesicles at specic mucosal sites.
Repeated viral waves may result in additional lesions close
to each other that may eventually coalesce. These lesions do
respond to preventive therapy, such as sun block or an antiviral drug. 2
For symptomatic treatment of both classical and nonclassical
lesions, there are numerous prescription and over-the-counter
drugs that focus on treating the symptoms. Generally, these
include agents with anesthetic properties (local anesthetics,
antihistamines), antipruritics, antivirals, emollients and
protectants.
Sodium lauryl sulfate has recently been shown to enhance
the effectiveness of other antiviral drugs when included at a
5% concentration, presumably by enhancing absorption of the
antiviral drug. 3
Combination therapy has recently been discussed as being
benecial. In the past, patients have been warned not to
use corticosteroids to treat cold sores with a rationale that

Table 2. General Treatment and Counseling Points for

Cold Sores.
1. Cleanse the area using a mild soap and pat dry with disposable
wipes.
2. Apply skin protectants (emollients) 45 times daily to relieve
dryness and keep lesions soft; otherwise, they may become dry
and crack, resulting in greater susceptibility to infection.
3. Topical local anesthetics in an emollient vehicle can relieve
burning, itching and pain.
4. If infected, use a triple antibiotic ointment; oral antibiotics may be
used if indicated.
5. If lesions persist longer than 14 days, contact your physician.
6. Wash hands frequently throughout the day.
7. Avoid factors that may delay the healing process, such as stress,
local trauma, wind, sunlight and fatigue.
8. If susceptible to cold sores, use a lip and face sunscreen
routinely.
9. Lesions are contagious, so minimize contact with others and do
not share cosmetics, etc.
10. Treatment is symptomatic and will relieve only the itching
and pain.

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International Journal of Pharmaceutical Compounding
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Vol. 8 No. 3 May/June 2004

B A S I C S

suppression of the inammatory response may cause a larger

lesion through coalescence. However, a combination of an
antiviral with a corticosteroid may overcome this problem.
The antiviral compound may suppress the infection by interrupting viral replication (controlling lesion spread), and the
corticosteroid may accelerate healing and suppress the inammatory response. 2
Table 1 lists many commonly used drugs for the prevention
and treatment of cold sores along with their usual strengths.
Three primary goals in treatment of cold sores include the
following:
1. Relieve pain and discomfort.
2. Prevent secondary bacterial infection.

3. Prevent the spread to others.

In treating a cold sore and counseling a patient, there are
several points to remember, as seen in Table 2.

Dosage Forms Used to Treat Cold Sores

The most common dosage forms used to treat cold sores include topicals and oral capsules/tablets. For purposes of this
article, we will limit the discussion to topical dosage forms.
The most convenient dosage form for application to a cold
sore would be a medication stick. After application, it is best if
a thin layer of the medication is removed and discarded to prevent reinfection. Medication sticks should never be shared.
Lip ointments, creams and gels are commonly used; they are

Example Formulations
Sticks
Rx
Acyclovir 5%, Lidocaine 1% and Sodium Lauryl Sulfate
5% Medication Stick
(Water-soluble base)
Acyclovir
5g
Lidocaine
1g
Sodium lauryl sulfate
5g
Polyethylene glycol 3350
26 g
Polyethylene glycol 300
63 g
1. Comminute the powders and blend them together.
2. Melt the PEG bases together at about 55C.
3. Incorporate the powders and mix until uniform.
4. Cool slightly, then pour into medication stick tubes.
Rx
Acyclovir 5%, Lidocaine 1% and Sodium Lauryl Sulfate
5% Medication Stick
(Water-proof base)
Acyclovir
5g
Lidocaine
1g
Sodium lauryl sulfate
5g
White wax
5g
Flavor
qs
Hydrophilic petrolatum
(Aquaphor, Aquabase)
qs
100 g
1. Comminute the powders and blend them together.
2. Melt the white wax and hydrophilic petrolatum together until fluid.
3. Incorporate the powders and mix until uniform.
4. Cool slightly, add flavor if desired, then pour into medication
stick tubes.

Ointments
Rx
Emollient Lip Balm with 5% Benzocaine
Benzocaine
Wheat germ oil
Olive oil
Cocoa butter

208

5g
10 g
10 g
75 g

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1. Pulverize the benzocaine and mix with the wheat germ oil and the
olive oil.
2. Using very low heat, soften the cocoa butter and incorporate the
benzocaine mixture and mix well.
3. Pour into appropriate containers and cool.
4. Package and label.
Rx
Fever Blister Ointment
Tannic acid
6g
Camphor
9g
Phenol
3g
Benzocaine
2g
Alcohol
qs
Hydrophilic petrolatum
(Aquabase, Aquaphor)
qs
100 g
1. Mix the camphor and phenol together.
2. Add the benzocaine followed by the tannic acid.
3. Add sufficient alcohol to dissolve the mixture.
4. Slowly add the solution to the hydrophilic petrolatum vehicle and mix
until uniform.
5. Package and label.

Creams
Rx
Deoxy-D-Glucose 0.2%, Lidocaine Hydrochloride 5% and Sodium
Lauryl Sulfate 5% Cream
Deoxy-D-glucose
200 mg
Lidocaine hydrochloride
5g
Sodium lauryl sulfate
5g
Propylene glycol
5 mL
Hydrophilic ointment
qs
100 g
1. Comminute the powders and blend them together.
2. Add the propylene glycol and form a smooth paste.
3. Incorporate into the hydrophilic ointment (Dermabase, Vanicream,
Velvachol) geometrically and mix until uniform.
4. Package and label.

B A S I C S

generally emollient and relatively easy to apply. It is best that a

nger cot or cotton-tipped applicator be used to remove the
ointment and apply to the stick; once used, the patient discards
the applicator stick. This minimizes reinfection. It is best not
to use a nger to remove the ointment and apply to the lips
because the nger can then become contaminated. Hands
should be thoroughly cleansed before and after each application. Creams and gels generally do not have the staying power of ointments. They can be prepared, however, to have
greater penetrating ability for the active drug. Topical liquids
can be used but must contain either a viscosity-increasing
agent or a volatile solvent so the liquid does not spread outside
the area to be treated. Formerly, compound benzoin tincture

was used on cold sores as a protectant. Topical liquids are not

used much anymore.
Note: Example formulations are provided.

References
1. Tierney LM, McPhee SJ, Papadakis MA, eds. Current Medical Diagnosis
& Treatment. 42nd ed. New York: McGraw-Hill; 2003; 102-104, 1304-1307.
2. Raborn GW, Grace MG. Recurrent herpes simplex labialis: Selected therapeutic options. J Can Dent Assoc 2003; 69(8): 498-503.
3. Piret J, Desormeaux A, Cormier H et al. Sodium lauryl sulfate increases
the efficacy of a topical formulation of foscarnet against herpes simplex
virus type 1 cutaneous lesions in mice. Antimicrob Agents and Chemother 2000; 44(9): 2263-2270.

Rx

Rx

Lemon Balm 1% Cream

Lemon balm, dried extract
1g
Lidocaine hydrochloride
5g
Glycerin
5g
Hydrophilic ointment
(Dermabase, Vanicream)
qs
100 g
1. Mix the lemon balm dried extract and the lidocaine hydrochloride
with the glycerin to form a smooth paste.
2. Incorporate into the hydrophilic ointment vehicle and mix until
uniform.
3. Package and label.

Foscarnet 3% and Sodium Lauryl Sulfate 5% Topical Gel

Foscarnet
3g
Sodium lauryl sulfate
5g
Pluronic F127
18 g
Purified water
qs
100 g
1. Mix the foscarnet and sodium lauryl sulfate with about 75 mL of
purified water.
2. Place in the refrigerator until cold.
3. Add the Pluronic F127 and sufficient purified water to volume and
mix well.
4. Place in the refrigerator and allow to set overnight.
5. Package and label.

Gels
Rx
Acyclovir 5% and Lidocaine Hydrochloride 2% Topical Gel
Acyclovir
5g
Lidocaine hydrochloride
2g
Methylcellulose
3g
Methylparaben
100 mg
Propylparaben
50 mg
Purified water
qs
100 g
1. Heat 50 mL of purified water to boiling.
2. Disperse the parabens and the methylcellulose and mix well.
3. Add the acyclovir and lidocaine to about 40 mL of preserved water.
4. Blend the two mixtures.
5. Add sufficient preserved water to volume and mix well.
6. Package and label.
Rx
Acyclovir 5% and Sodium Lauryl Sulfate 5% Topical Gel
Acyclovir
5g
Sodium lauryl sulfate
5g
Pluronic F127
18 g
Purified water
qs
100 g
1. Mix the acyclovir and sodium lauryl sulfate with about 75 mL of
purified water.
2. Place in the refrigerator until cold.
3. Add the Pluronic F127 and sufficient purified water to volume and
mix well.
4. Place in the refrigerator and allow to set overnight.
5. Package and label.

Rx
Acyclovir 5% and Dexamethasone 0.1% Topical Gel
Acyclovir
5g
Dexamethasone
100 mg
Pluronic F127
18 g
Purified water
qs
100 g
1. Mix the acyclovir and dexamethasone with about 75 mL of purified
water.
2. Place in the refrigerator until cold.
3. Add the Pluronic F127 and sufficient purified water to volume and
mix well.
4. Place in the refrigerator and allow to set overnight.
5. Package and label.
Rx
Foscarnet 3% and Triamcinolone Acetonide 0.1% Topical Gel
Foscarnet
3g
Triamcinolone acetonide
100 mg
Pluronic F127
18 g
Purified water
qs
100 g
1. Mix the foscarnet and triamcinolone acetonide with about 75 mL of
purified water.
2. Place in the refrigerator until cold.
3. Add the Pluronic F127 and sufficient purified water to volume and
mix well.
4. Place in the refrigerator and allow to set overnight.
5. Package and label.

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