Penciclovir, the active metabolite of famciclovir, is marketed as a topical cream for the treatment of recurrent herpes labialis in patients 12 years of age and older. The drug is applied topically every 2 hours during waking hours for 4 days, and should be started as soon as possible (during the prodrome or when lesions appear). When penciclovir therapy is initiated within 1 hour of the signs or symptoms of herpes labialis, mean lesion duration is about 0.7 to 1 day shorter than without treatment. Penciclovir is only indicated for use on lesions of the face and lip; not recommended for application to mucous membranes. Additionally, the efficacy of penciclovir has not been established in patients who are immunocompromised.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Topical Administration
-Apply topically to lesions on the lips and face. Application to mucous membranes is not recommended.
-Avoid application on or near the eyes.
In two double-blind, placebo-controlled trials, 1,516 patients were treated with penciclovir cream and 1,541 with placebo vehicle. The incidence of adverse events was similar for both treatment groups and there were no adverse reactions reported more frequently with penciclovir than with placebo. Local application site reactions (skin irritation) were reported by 1% of the patients treated with penciclovir and 2% of placebo-treated patients. Other adverse events reported by less than 1% of both penciclovir-treated and vehicle only-treated patients included hypoesthesia, erythematous rash, and dysgeusia or taste perversion. It is not clear if these adverse events were due to the active drug or the cream base. In two studies which evaluated the dermal tolerance of 5% penciclovir cream (a 5-fold higher concentration than the commercially available product) using occluded patch testing methodology, penciclovir 5% cream induced mild erythema in about 50% of subjects. The irritancy profile was similar to the vehicle control in terms of severity and proportion of subjects with a response. No evidence of sensitization was observed.
Adverse events reported with postmarketing use of penciclovir in adults include headache, oral or pharyngeal edema, parosmia, aggravated condition, decreased therapeutic response, local edema, pain, paresthesias, pruritus, skin discoloration, and urticaria.
Penciclovir is contraindicated in patients with penciclovir hypersensitivity. Additionally, since penciclovir is the active metabolite of famciclovir, penciclovir is contraindicated in patients with a history of famciclovir hypersensitivity. Because of similar chemical structures and possible cross-sensitivity, use penciclovir with caution in patients with acyclovir hypersensitivity, ganciclovir hypersensitivity, valacyclovir hypersensitivity, or valganciclovir hypersensitivity. Alternative agents such as foscarnet or cidofovir may be suitable since they are not structurally related to these antivirals.
Avoid ophthalmic administration of penciclovir, as ocular exposure may cause irritation. Administer the drug only on herpetic lesions of the lips and face. Due to a lack of data, application to mucous membranes is not recommended.
The efficacy of penciclovir has not been established in patients with immunosuppression.
No adequate and well-controlled studies have been conducted regarding the use of penciclovir during pregnancy; however, because penciclovir is not systemically absorbed following topical application, fetal drug exposure is not expected.
It is not known if penciclovir is excreted in human milk; however, because penciclovir is not systemically absorbed following topical application, fetal drug exposure is not expected. Potential alternatives to consider during breast-feeding include acyclovir and valacyclovir. However, patient factors, local susceptibility patterns, and specific microbial susceptibility should be assessed before choosing an alternative agent. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Per the manufacturer, this drug has been shown to be active against most strains of the following microorganisms either in vitro and/or in clinical infections: herpes simplex virus type 1, herpes simplex virus type 2
NOTE: The safety and effectiveness in treating clinical infections due to organisms with in vitro data only have not been established in adequate and well-controlled clinical trials.
This drug may also have activity against the following microorganisms: varicella-zoster virus
NOTE: Some organisms may not have been adequately studied during clinical trials; therefore, exclusion from this list does not necessarily negate the drug's activity against the organism.
For the treatment of recurrent herpes labialis:
Topical dosage:
Adults: Apply cream every 2 hours while awake for 4 days beginning as soon as possible after onset of symptoms (during the prodrome or when lesions appear).
Children and Adolescents 12 years and older: Apply cream every 2 hours while awake for 4 days beginning as soon as possible after onset of symptoms (during the prodrome or when lesions appear).
Maximum Dosage Limits:
-Adults
No maximum dosage information is available.
-Geriatric
No maximum dosage information is available.
-Adolescents
No maximum dosage information is available.
-Children
12 years: No maximum dosage information is available.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with Penciclovir products.
Penciclovir is a deoxynucleoside analog DNA polymerase inhibitor with activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). In cells infected with HSV-1 or HSV-2, viral thymidine kinase phosphorylates penciclovir to a monophosphate form. The monophosphate form of the drug is then converted to penciclovir triphosphate by cellular kinases. The intracellular triphosphate of penciclovir is retained in vitro inside HSV-infected cells for 10 to 20 hours, compared with 0.7 to 1 hour for acyclovir. In vitro studies show that penciclovir triphosphate selectively inhibits viral DNA polymerase by competing with deoxyguanosine triphosphate. Inhibition of DNA synthesis of virus-infected cells inhibits viral replication.
In cell culture studies, reduced susceptibility to penciclovir has been observed in HSV-1 and HSV-2 isolates with mutations in the viral thymidine kinase (TK) and DNA polymerase (POL) genes. These mutations lead to a decreased amount of viral thymidine kinase, and consequently a reduction in the initial phosphorylation of penciclovir. HSV resistance should be considered in patients who fail to respond or experience recurrent viral shedding during penciclovir therapy. Similar TK and POL mutations have been identified in HSV isolates from patients who have failed acyclovir therapy. Cross-resistance to penciclovir has been observed in acyclovir-resistant HSV-1 and HSV-2 isolates with TK and POL mutations and in foscarnet-resistant HSV-1 isolates with POL mutations.
Penciclovir cream is applied topically to lesions on the lips or face.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Topical Route
Penciclovir is not absorbed systemically following topical administration. In a study involving healthy male volunteers (n = 12), measurable penciclovir concentrations were not detected in the plasma or urine following single or repeat topical applications of the 1% cream at a dose of 180 mg daily (approximately 67-times the estimated usual clinical dose).
-Special Populations
Pediatrics
Systemic absorption of penciclovir following topical administration has not been evaluated in patients younger than 18 years of age.