placebo vehicle. While there was no statistically significant
effect on pain, observed differences in healing time (nine days
for those treated with the active drug vs 10.1 days for control
subjects), on average, was statistically significant.8
5. Topical Mucoadhesive Acyclovir (Lauriad®)
Acyclovir Lauriad is a new topical agent approved in 2013
for the treatment of RHL. A single buccal application of a
mucoadhesive tablet is applied to the gum above the canine
incisor at the onset of prodromal symptoms. Patients hold
the tablet in place for 30 seconds and acyclovir is absorbed
into the labial mucosa for the next six to eight hours. In a
recent study, researchers enrolled 775 immunocompetent
patients who had at least four episodes of RHL in the past
year and who were able to recognize their prodromal symptoms.
378 patients were randomized to receive the acyclovir
buccal tablet, while 397 were randomized to receive placebo.
A total of 330 patients had recurrence of a primary vesicle,
but significantly fewer, 149 (64.2%) in the treatment group
vs. 181 (73.6%) in the control group. The time to the next
recurrence in the treatment group was 304 days compared to
199 days for the placebo group. It is postulated that having a
high salivary concentration and high mucosal concentration
of acyclovir during the time of highest viral replication may
modify the clinical course of labial herpes.9,10
II. Oral Systemic Antiviral Agents
1. Acyclovir (Zovirax®)
Although not FDA approved for RHL, oral acyclovir (200mg-
400mg, five times a day) used off-label is an effective treatment
for RHL. Several studies have shown a reverse in healing time
by 1 to 1.5 days compared to placebo.11,12
2. Valacyclovir (Valtrex®)
Valacyclovir, the prodrug of acyclovir, is FDA approved for the
treatment of RHL. It is associated with three to five times the
bioavailability of acyclovir. A dosage of 2000 mg bid for one
day has been shown to improve healing time compared to
placebo (0.5 to 1 day reduction) and to decrease downtime of
pain compared to placebo (0.5 to 0.7 day reduction).13
Valacyclovir also approved by the FDA for patients with frequent
episodes of RHL. Two studies evaluated the efficacy
of oral valacyclovir 500 mg daily compared with placebo
for the suppression of herpes labialis in those who had four
or more episodes in the antecedent year. Daily suppressive
therapy was administered for four months. 60% of the subjects
who took valacyclovir remained recurrence free during
the four months, compared to 38% who were treated with
the placebo.14
3. Famciclovir (Famvir®)
Famciclovir, the prodrug of penciclovir, is FDA approved for
treating RHL, with a more convenient dosing schedule (1500
mg as a single dose). Famciclovir is also FDA cleared for use
in episodic therapy as well as daily suppressive therapy in immunosuppressed
patients.15
III. Antiviral Agents
Complicated HSV-1 infections, cutaneous and/or visceral dissemination,
and severe infections in immunocompromised
patients should be treated promptly with intravenous acyclovir.
For those patients who have acyclovir-resistant HSV
strains, IV foscarnet or cidofovir may be useful.1
IV. Emerging Trends: Combination of Oral Antiviral with Topical Steroid
Treatment combining oral acyclovir with topical clobetasol
gel may be synergistic. A recent pilot study combining valacyclovir
2000 mg bid for one day and clobetasol gel 0.05% bid
for three days vs a combination of placebo pills and cream
saw a mean healing time of 5.8 days compared to 9.3 days in
placebo.16 Another study evaluated the combination of oral
famciclovir and topical fluocinonide gel vs famciclovir plus
placebo cream in 29 subjects. There was a 70% reduction in
herpes lesions size when the combination treatment was administered
after the onset of prodromal symptoms, but there
was no difference in healing time between the two groups.17
Conclusion
The treatment of RHL remains a challenge in the 21st century.
The herpes virus is ubiquitous, and no effective vaccine to protect
against it has been developed thus far. Fortunately, there
are many oral and topical treatments for RHL that provide some
improvement in healing time and pain relief. Future research
will undoubtedly lead to advances in the discovery of new,
more effective therapeutic agents, combination of drugs and
more efficient delivery systems.
Disclosure
Dr. Sarnoff has no relevant conflicts of interest to disclose.
References
- Eastern JS, James, WD, et al. Dermatologic manifestations of herpes simplex. Medscape .2013
- Lin L, Chen XS, Cui PG, et al. Topical Penciclovir Clinical Study Group. Topical application of penciclovir cream for the treatment of herpes simplex facialis/ labialis: a randomized, doubleblind, multicentre, aciclovir-controlled trial. J Dermatolog Treat 13(2):67-72 (2002 Jun).
- Rooney JF, Straus SE, Mannix ML, et al. Oral acyclovir to suppress frequently recurrent herpes labialis. A double-blind, placebocontrolled trial. Ann Intern Med 118(4):268-72 (1993 Feb).
- 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 AcadDermatol 45(2):222-30 (2001 Aug).
- Spruance SL, Nett R, Marbury T, et al. Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother 46(7):2238-43 (2002 Jul).
