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  • CLASSES

    Topical Antivirals

    DEA CLASS

    Rx

    DESCRIPTION

    Topical antiviral medication; active metabolite of famciclovir
    For treatment of herpes labialis in patients 12 years and older
    More favorable results than with topical acyclovir

    COMMON BRAND NAMES

    Denavir

    HOW SUPPLIED

    Denavir/Penciclovir Sodium Topical Cream: 1%

    DOSAGE & INDICATIONS

    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).[46977]

    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

    Adults

    No maximum dosage information is available.

    Elderly

    No maximum dosage information is available.

    Adolescents

    No maximum dosage information is available.

    Children

     >= 12 years: No maximum dosage information is available.
     < 12 years: Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment is recommended for topical therapy. The pharmacokinetics of penciclovir have not been evaluated in patients with severe uncompensated hepatic impairment.

    Renal Impairment

    No dosage adjustment needed for topical therapy.

    ADMINISTRATION

    Topical Administration

    Penciclovir is administered topically to lesions on the lips and face. Application to mucous membranes is not recommended.
    Avoid application on or near the eyes.

    STORAGE

    Denavir:
    - Store at controlled room temperature (between 68 and 77 degrees F)

    CONTRAINDICATIONS / PRECAUTIONS

    Acyclovir hypersensitivity, famciclovir hypersensitivity, ganciclovir hypersensitivity, penciclovir hypersensitivity, valacyclovir hypersensitivity, valganciclovir hypersensitivity

    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, penciclovir should be used 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.

    Ophthalmic administration

    Penciclovir should only be used on the lips and face. Because no data are available, application to human mucous membranes is not recommended. Penciclovir cream is not for ophthalmic administration; care should be taken to avoid application in or near the eyes since the drug may cause irritation.

    Immunosuppression

    The efficacy of penciclovir has not been established in patients with immunosuppression.

    Pregnancy

    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.[46977]

    Breast-feeding

    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.

    Children, infants, neonates

    Penciclovir is safe and effective in adolescents and children 12 years and older; safety and efficacy in neonates, infants and children less than 12 years of age have not been established.

    ADVERSE REACTIONS

    Moderate

    erythema / Early / 50.0-50.0
    edema / Delayed / 0-1.0

    Mild

    headache / Early / 5.3-5.3
    skin irritation / Early / 1.3-1.3
    parosmia / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    skin discoloration / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    hypoesthesia / Delayed / 0.9-0.9
    dysgeusia / Early / 0.2-0.2

    DRUG INTERACTIONS

    There are no drug interactions associated with Penciclovir products.

    PREGNANCY AND LACTATION

    Pregnancy

    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.[46977]

    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.

    MECHANISM OF ACTION

    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.[46977]

    PHARMACOKINETICS

    Penciclovir cream is applied topically to the lips or face. Application to mucous membranes is not recommended.

    Topical Route

    In a study of healthy male volunteers, measurable penciclovir concentrations were not detected in plasma or urine following single or repeat application of the 1% cream at a dose of 180 mg penciclovir daily (about 67 times the estimated usual clinical dose).