VA Class:DE103
ATC Class:D06BB06
Penciclovir, a synthetic acyclic guanine nucleoside analog, is an antiviral agent active against various Herpesviridae, including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2).1, 2, 5, 11, 14, 25, 27, 28, 29
Penciclovir 1% cream is used for the topical treatment of recurrent herpes labialis (orofacial or orolabial herpes, cold sores, fever blisters) in immunocompetent individuals.1, 2, 6, 7, 8, 22, 23
Efficacy of topical penciclovir has not been established in immunocompromised patients;1 clinical trials evaluating topical penciclovir for the treatment of herpes labialis included only immunocompetent individuals.1, 2, 7 In individuals with human immunodeficiency virus (HIV) infection, oral antivirals (e.g., acyclovir, famciclovir, valacyclovir) usually are recommended for the treatment of orolabial lesions caused by herpes simplex virus (HSV).155 Topical treatment of herpes labialis generally is less effective than oral treatment.22, 23
Topical application of penciclovir 1% cream to herpes labialis lesions in immunocompetent patients decreases the duration of pain and time required for crusting and healing of lesions.1, 2, 6, 7 However, the clinical benefit of topical penciclovir in such patients is modest and treatment with the drug shortens the principal clinical end points (e.g., duration of pain, healing time, duration of viral shedding) on average by less than 1 day (e.g., by 0.3-0.7 days).1, 2, 6, 7 In clinical studies, efficacy of topical penciclovir was evident whether therapy was initiated at the prodromal or erythemal lesion (early) stage versus at the papular or vesicular (late) stage.2, 7 There is no evidence that topical antiviral therapy can eradicate latent virus or affect the subsequent risk, frequency, or severity of recurrences after such therapy is discontinued.21
In a large vehicle-controlled study in immunocompetent adults with recurrent herpes simplex labialis, topical penciclovir 1% cream self-initiated within 1 hour of the first sign or symptom and reapplied every 2 hours while awake for 4 days resulted in pain resolution and cutaneous healing in a median of 3.5 and 4.8 days, respectively; the corresponding response rates for vehicle cream were a median of 4.1 and 5.5 days, respectively, and the differences were statistically significant.2 Similar results for pain resolution and cutaneous healing have been reported in another large placebo-controlled study.7 In both studies, the incidence and severity of adverse effects were similar in penciclovir- and vehicle-treated patients.1, 2, 7
Penciclovir 1% cream is applied topically to herpes labialis lesions on the lips and surrounding symptomatic skin on the face (e.g., areas with tingling).1
Penciclovir 1% cream should not be applied in or near the eyes.1 The cream should not be applied to mucous membranes.1 (See Administration Precautions under Cautions: Warnings/Precautions.)
Prior to topical application of penciclovir 1% cream, the face should be cleaned and dried.1
A sufficient amount of the cream should be applied to adequately cover all lesions on the lips and surrounding symptomatic skin on the face (e.g., areas with tingling);1 the cream should be rubbed gently until it disappears.1
Hands should be washed with soap and water prior to and following application of the cream.1
Penciclovir 1% cream should be stored at 20-25°C, but may be exposed to 15-30°C.1
For the topical treatment of herpes labialis (orofacial or orolabial herpes, cold sores, fever blisters) in adults and children 12 years of age or older, penciclovir 1% cream should be applied every 2 hours during waking hours for 4 days.1 The amount of cream used should be sufficient to cover all lip lesions and surrounding symptomatic skin on the face (e.g., areas with tingling). 1 (See Topical Administration under Dosage and Administration: Administration.)
Treatment with topical penciclovir should be initiated at the earliest sign or symptom of herpes labialis (i.e., tingling, redness, itching, presence of a bump).1
If lesions worsen or do not improve, they should be evaluated for secondary bacterial infection.1 The possibility of resistance to penciclovir also should be considered.1
There are no special population dosage recommendations for topical penciclovir.1
Penciclovir 1% cream is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.1
In vehicle-controlled dermal tolerance studies in healthy individuals performed using topical application and repeated, occluded patch testing, penciclovir 5% cream (fivefold higher concentration than the commercially available cream) induced mild erythema in approximately 50% of study participants.1 In terms of severity and incidence, this irritancy profile was similar to that of the vehicle control.1 There was no evidence that topical penciclovir cream causes sensitization.1
There have been postmarketing reports of local edema, pain, paresthesia, pruritus, skin discoloration, and urticaria in patients treated with topical penciclovir 1% cream.1
Penciclovir 1% cream is for topical use only on the lips and surrounding symptomatic skin on the face (e.g., areas with tingling).1
Penciclovir 1% cream should not be applied in or near the eyes since the drug may cause irritation.1
The cream should not be applied to mucous membranes since data are not available regarding use at these sites.1
Individuals with Altered Immunocompetence
Efficacy of penciclovir 1% cream has not been established in immunocompromised patients.1
Category B.1 (See Users Guide.)
Penciclovir 1% cream should be used during pregnancy only if clearly needed.1
There are no adequate and controlled studies using topical penciclovir in pregnant women.1 No adverse effects on the course and outcome of pregnancy or on fetal development were evident in rats and rabbits following IV administration of penciclovir at dosages of 80 and 60 mg/kg daily, respectively (equivalent to estimated human dosages of 13 and 18 mg/kg daily, respectively, based on body surface area conversion).1
It is not known whether penciclovir is distributed into human milk following topical application.1 Although systemic absorption is minimal following topical application of penciclovir 1% cream to skin,1 oral administration of famciclovir (the oral prodrug of penciclovir) in lactating rats results in penciclovir concentrations in milk that are higher than those in plasma.1
A decision should be made whether to discontinue nursing or penciclovir 1% topical cream, taking into account the importance of the drug to the mother.1
Safety and efficacy of penciclovir 1% cream have not been established in children younger than 12 years of age.1 Data are not available regarding safety of penciclovir in neonates.1
The frequency of adverse reactions following topical application of penciclovir 1% cream in children and adolescents 12-17 years of age with recurrent herpes labialis is similar to that reported in adults.1
The adverse effects profile of penciclovir 1% cream in adults 65 years of age or older is similar to that reported in younger adults.1
In clinical trials, the incidence and type of adverse effects reported in patients treated with topical penciclovir 1% cream were similar to those reported in patients treated with vehicle control cream.1, 2, 7 In those treated with topical penciclovir 1% cream, application site reactions (localized irritation, hypesthesia/local anesthesia) occurred in 1-3% 1, 2 and taste perversion and erythematous rash occurred in less than 1%.1
Formal drug interaction studies have not been performed to date with penciclovir 1% topical cream.1
Clinically important drug interactions are unlikely since systemic absorption is minimal following topical application of penciclovir 1% cream to skin.1
Penciclovir is not appreciably absorbed into systemic circulation following topical application of penciclovir 1% cream to skin.1, 5
Following single or repeated application of penciclovir 1% cream at a dosage of 180 mg daily (approximately 67 times the estimated usual topical dosage) in healthy adults, the drug was not detected in plasma or urine.1, 5 Systemic absorption of the drug following topical application has not been evaluated in children or adolescents younger than 18 years of age.1
Results of an in vitro study using cadaver skin indicate that the drug penetrates the skin following topical application of penciclovir 1% cream;24 approximately 3% of the topical dose is found in the stratum corneum and epidermis layers.24
Penciclovir is converted in vivo to penciclovir triphosphate, the pharmacologically active metabolite.1, 5, 11, 14, 25, 27 Intracellular conversion of penciclovir to the triphosphate is necessary for the antiviral activity of the drug.1, 5, 11, 14, 25, 27 (See Description.) Although the clinical importance is unknown, penciclovir triphosphate has an intracellular half-life of 10 or 20 hours in herpes simplex virus types 1 or 2 (HSV-1 or HSV-2), respectively.1
Penciclovir, a synthetic acyclic guanine nucleoside analog, is an antiviral agent.1, 2, 5, 11, 14, 25, 27, 28, 29 Penciclovir is structurally and pharmacologically related to acyclovir.5, 11, 14, 27, 28, 29
Penciclovir is converted in vivo to a pharmacologically active triphosphate metabolite, which has in vitro and in vivo inhibitory activity against various Herpesviridae,1, 5, 9, 11, 14, 25, 27, 28, 29 including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2)1, 5, 14, 25, 27 and varicella-zoster virus (VZV).5, 10, 13 The drug also has some in vitro activity against Epstein-Barr virus (EBV),5, 9, 10, 11 but only limited activity in vitro against cytomegalovirus (CMV).5, 11
Penciclovir triphosphate exerts its antiviral effects on HSV and VZV by interfering with DNA synthesis and inhibiting viral replication.1, 9 In virus-infected cells, penciclovir is converted to penciclovir monophosphate by viral thymidine kinase;1, 9, 27 the monophosphate is further converted to the diphosphate via cellular kinase and then to the triphosphate via other cellular enzymes.1, 9, 27, 29 Penciclovir triphosphate is a viral DNA polymerase inhibitor and stops replication of viral DNA by competing with deoxyguanosine triphosphate for viral DNA polymerase and inhibiting viral DNA chain elongation.1, 27 The inhibitory activity of penciclovir triphosphate is highly selective because of the drug's affinity for thymidine kinase encoded by HSV and VZV.1, 9 The mechanism of action of penciclovir is similar to that of acyclovir.27, 28 Although penciclovir has a higher affinity for HSV thymidine kinase than acyclovir and penciclovir triphosphate is more stable than acyclovir triphosphate in HSV-infected cells, HSV DNA polymerases have a higher affinity for acyclovir triphosphate than for penciclovir triphosphate and the net effect is that these nucleoside analogs have similar antiviral potencies.27
Although most HSV isolates tested have been susceptible to penciclovir in vitro and intermittent topical use of the drug does not appear to be associated with emergence of penciclovir resistance,25, 26, 27 HSV resistant to penciclovir have been produced in vitro and penciclovir-resistant clinical isolates have been reported rarely.1, 25, 26, 27 HSV clinical isolates resistant to acyclovir because they are deficient in viral thymidine kinase (i.e., thymidine kinase-negative mutants) generally are cross-resistant to penciclovir.1, 5, 8, 14, 15, 27, 28 However, some viral thymidine kinase- or DNA polymerase-altered strains that are resistant to acyclovir have been susceptible to penciclovir in vitro.5, 8, 11, 13, 14, 27
For the topical treatment of herpes labialis, penciclovir is commercially available as a 1% cream.1 Each gram of the white cream contains 10 mg of penciclovir and cetostearyl alcohol, mineral oil, polyoxyl 20 cetostearyl ether, propylene glycol, purified water, and white petrolatum.1 Following topical application of penciclovir to skin, the drug is not appreciably absorbed into systemic circulation, even at single or multiple dosages up to 180 mg daily (approximately 67 times the estimated usual topical dosage).1, 5 Penciclovir has limited oral bioavailability (about 5%).5 A prodrug of penciclovir, famciclovir, is commercially available for oral use.5, 27 (See Famciclovir 8:18.32.)
Importance of using topical penciclovir 1% cream only for the treatment of recurrent herpes labialis (orofacial or orolabial herpes, cold sores, fever blisters) on the lips and surrounding symptomatic skin on the face (e.g., areas with tingling).1
Importance of avoiding application in or near the eyes.1
Advise patients that penciclovir topical cream is not a cure for cold sores and that not all patients will respond to treatment with the cream.1
Importance of starting treatment at the earliest sign of a cold sore (i.e., tingling, redness, itching, bump).1
Advise patients to ensure that their face is clean and dry prior to application of penciclovir topical cream and to wash their hands with soap and water prior to and after applying the cream.1
Advise patients not to use penciclovir topical cream if they have had an allergic reaction to the drug or any ingredient in the formulation.1
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1
Importance of advising patients of other important precautionary information.1 (See Cautions.)
Additional Information
Overview® (see Users Guide). For additional information on this drug until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Topical | Cream | 1% | Denavir® | Prestium |
AHFS® Drug Information. © Copyright, 1959-2025, Selected Revisions February 23, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Prestium Pharma, Inc. Denavir® (penciclovir) topical cream 1% prescribing information. Newtown, PA; 2013 Sep.
2. Spruance SL, Rea TL, Thoming C et al. Penciclovir cream for the treatment of herpes simplex labialis. A randomized, multicenter, double-blind, placebo-controlled trial. Topical Penciclovir Collaborative Study Group. JAMA . 1997; 277:1374-9. [PubMed 9134943]
5. Alrabiah FA, Sacks SL. New antiherpesvirus agents. Drugs . 1996; 52:17-32. [PubMed 8799682]
6. Lin L, Chen XS, Cui PG et al. Topical application of penciclovir cream for the treatment of herpes simplex facialis/labialis: a randomized, double-blind, multicentre, aciclovir-controlled trial. J Dermatolog Treat . 2002; 13:67-72. [PubMed 12060504]
7. 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; 133:303-9. [PubMed 11934185]
8. Boyd MR, Safrin S, Kern ER. Penciclovir: a review of its spectrum of activity, selectivity and cross-resistance patterns. Antiviral Chem Chemother . 1993; 4(Suppl 1): 3-11.
9. Bacon TH, Boyd MR. Activity of penciclovir against Epstein-Barr virus. Antimicrob Agents Chemother . 1995; 39:1599-1602. [PubMedCentral][PubMed 7492112]
10. Gnann JW Jr. New antivirals with activity against varicella-zoster virus. Ann Neurol . 1994; 34:S69-72.
11. Kulikowski T. Structure-activity relationships and conformational features of antiherpetic pyrimidine and purine nucleoside analogues: a review. Pharm World Sci . 1994; 16:127-138. [PubMed 8032338]
13. Hasegawa T, Kurokawa M, Yukawa TA et al. Inhibitory action of acyclovir (ACV) and penciclovir (PCV) on plaque formation and partial cross-resistance of ACV-resistant varicella-zoster virus to PCV. Antiviral Res . 1995; 27:271-9. [PubMed 8540749]
14. Safrin S, Phan L. In vitro activity of penciclovir against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus. Antimicrob Agents Chemother . 1993; 37:2241-3. [PubMedCentral][PubMed 8257152]
15. Talarico CL, Phelps WC, Biron KK. Analysis of the thymidine kinase genes from acyclovir-resistant mutants of varicella-zoster virus isolated from patients with AIDS. J Virol . 1993; 67:1024-33. [PubMedCentral][PubMed 8380452]
21. SmithKline Beecham, Philadelphia, PA: Personal communication.
22. Fatahzadeh M, Schwartz RA. Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management. J Am Acad Dermatol . 2007; 57:737-63; quiz 764-6. [PubMed 17939933]
23. Usatine RP, Tinitigan R. Nongenital herpes simplex virus. Am Fam Physician . 2010; 82:1075-82. [PubMed 21121552]
24. Hasler-Nguyen N, Shelton D, Ponard G et al. Evaluation of the in vitro skin permeation of antiviral drugs from penciclovir 1% cream and acyclovir 5% cream used to treat herpes simplex virus infection. BMC Dermatol . 2009; 9:3. [PubMedCentral][PubMed 19341466]
25. Sarisky RT, Bacon T, Boon R et al. Penciclovir susceptibilities of herpes simplex virus isolates from patients using penciclovir cream for treatment of recurrent herpes labialis. Antimicrob Agents Chemother . 2002; 46:2848-53. [PubMedCentral][PubMed 12183237]
26. Shin YK, Weinberg A, Spruance S et al. Susceptibility of herpes simplex virus isolates to nucleoside analogues and the proportion of nucleoside-resistant variants after repeated topical application of penciclovir to recurrent herpes labialis. J Infect Dis . 2003; 187:1241-5. [PubMed 12696003]
27. Bacon TH, Levin MJ, Leary JJ et al. Herpes simplex virus resistance to acyclovir and penciclovir after two decades of antiviral therapy. Clin Microbiol Rev . 2003; 16:114-28. [PubMedCentral][PubMed 12525428]
28. Piret J, Boivin G. Resistance of herpes simplex viruses to nucleoside analogues: mechanisms, prevalence, and management. Antimicrob Agents Chemother . 2011; 55:459-72. [PubMed 21078929]
29. De Clercq E, Field HJ. Antiviral prodrugs - the development of successful prodrug strategies for antiviral chemotherapy. Br J Pharmacol . 2006; 147:1-11. [PubMed 16284630]
155. Panel on Opportunistic Infections in HIV-infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (September 17, 2015). Updates may be available at HHS AIDS Information (AIDSinfo) website. [Web]