Pharmacology Update

Penciclovir Cream for Treatment of Cold Sores

By William T. Elliott, MD, and James Chan, PharmD, PhD

Penciclovir cream has been approved for the treatment of cold sores (herpes labialis). Penciclovir, an inhibitor of herpes simplex virus (HSV) polymerase, is manufactured by SmithKline Beecham and goes under the trade name Denavir.


Penciclovir cream is indicated for the treatment of recurrent herpes labialis in adults.

Potential Advantages

Data from two double-blind, placebo-controlled trials (n = 3057) showed that penciclovir, initiated within one hour of symptoms and applied every two hours, shortened the duration of lesion pain and duration of lesion and by about one-half day (3.9 vs 4.5 days and 4.5 vs 5 days, respectively). These differences were statistically significant.1

Potential Disadvantages

To be effective, therapy with penciclovir cream must be initiated within one hour of noticing signs or symptoms, such as pain or lip swelling, and must be administered every two hours while awake for four days. Side effects are generally mild and included headache and skin irritation. There are no data on the development of resistant strains of herpes simplex virus.

Dosing Information

Penciclovir cream is supplied as Denavir 1% cream (2 g). It should be started within one hour of onset of symptoms and applied every two hours thereafter while awake.


Penciclovir is an antiviral agent that inhibits HSV polymerase by competing with deoxyguanosine triphosphate, thus inhibiting replication. When applied during the prodrome phase and applied every two hours while awake thereafter, controlled clinical trials have shown penciclovir to be minimally effective, reducing the duration of lesion pain and the lesion itself by about one-half day. Its effectiveness in the real world setting may be somewhat less when appropriate onset of therapy and compliance may be factors. The only other available topical antiviral, acyclovir cream, has not been particularly effective either.2 Oral therapy with acyclovir (400 mg 5 times daily for 5 days starting in the prodrome or erythemic lesion stage) has shown to reduce duration of pain by 38% and mean healing time by 27%.3 A recent report suggests that famciclovir, the prodrug of penciclovir, administered at 500 mg tid for five days, reduced the duration of lesions by about three days in ultraviolet radiation-induced cold scores.4 For prophylaxis, oral acyclovir (400 mg bid) has been reported to be effective in suppressing herpes labialis in patients with recurrent disease (³ 6 episodes/year).5

Clinical Implications

Herpes labialis is a common condition, affecting an estimated one out of three Americans. A small percentage of patients (5-10%) report frequent recurrences (³ 6 per year).5 Colds sores are painful and uncomfortable and can be unsightly and embarrassing, causing lost time from work and social activities. Penciclovir cream is minimally effective in treating this condition and is expensive, at $17.49 for 2 g.


1. Denavir Product Monograph. SmithKline Beecham, October 1996.

2. O'Brien JJ, et al. Drugs 1989;37:233-309.

3. Spruance SL, et al. J Infect Dis 1990;161:185-190

4. Spruance SL, et al. 1995 Interscience Conference for Antimicrobial ????? MISSING TEXT????

5. Rooney JF. Ann Intern Med 1993;118:268-271.