Herpesviruses 2000: Penciclovir

Penciclovir is an antiviral drug that can be used either as topical cream or intravenously to treat herpes simplex virus (HSV-1, HSV-2) infections. It is currently licensed as Denavir© to treat herpes labialis, otherwise known as cold sores. In experimental stages currently, intravenous penciclovir could be used to treat HSV-1 and HSV-2 in immunocompromised hosts. A drug called famciclovir is the oral prodrug of penciclovir and is used to treat HSV-1, HSV-2, and VZV.

Penciclovir is a nucleoside deoxyguanosine analog that inhibits the DNA synthesis of herpesviruses. Because it is very poorly absorbed orally, famiclovir was developed to orally treat herpesvirus infections. Penciclovir enter all the cells of the body, both virus-infected and uninfected cells. In the virus-infected cells only, penciclovir is phosphorylated to its active form first by the viral thymidine kinase which adds the first phosphate and then by a cellular enzyme which completes the activation. In this way, penciclovir in its active triphosphate state is confined to the virus-infected cells. Once formed, penciclovir triphosphate has a very long intracellular half-life when compared with acyclovir triphosphate. Penciclovir triphosphate is now free to insert in the viral DNA as it is being formed in place of the nucleotide guanine and terminate the sequence, thus inhibiting replication of the virus.

Denavir© is a 1% topical cream used for the recurrent infection of HSV-1, herpes labilias, otherwise known as cold sores. Penciclovir has also been studied in its ability for acute intravenous therapy of herpes simplex virus disease in immunocompromised patients.

In randomized, double-blind, placebo-controlled, patient-initiated trials of Denavir©, the penciclovir-treated patients has shorter lesion-healing times, reduced symptoms, and shorter periods of viral shedding. Patients treated early and late in their episode had equivalent outcomes. Also from these studies came the hypothesis that penciclovir may keep lesions from becoming severe and therefore prevent severe attacks. Because of these positive effects, Denavir© became the first treatment for episodic use of herpes labialis in the United States.

For therapy of HSV-1 and HSV-2 in immunocompromised patients, penciclovir is equal in efficacy to acyclovir, but can be administered less frequently because of its extended half-life in the cell.

Denavir© is to be administered every two hours during the day for four days beginning in the prodrome or initial lesion period. It has been shown that HSV-1 can become resistant to penciclovir.

Intravenous penciclovir is not currently licensed as a treatment, but in clinical trials it was found that doses of 5mg per kg every twelve hours was as effective as acyclovir in treating HSV infections.

Denavir © is meant to topically treat cold sores on the lips and skin. It should not be applied to mucous membranes because it has not been studied for this use. Also, it should not be ingested or be applied near the eyes.

Denavir© is not recommended for children under 18 years of age, pregnant or nursing mothers, and its effects have not been studied in immunocompromised patients (although intravenous penciclovir produced no harmful effects).

Side effects of Denavir© in clinical trials were comparable to placebo side effects.

Side effects of intravenous penciclovir (seen in comparable rates in placebo) may be headache, abdominal pain, increased serum lipase, nausea, dyspepsia, dizziness, and hyperbilirubinemia.

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Lazarus, HM, et al. "Intravenous penciclovir for treatment of herpes simplex infections in immunocompromised patients: results of a multicenter, acyclovir-controlled trial. The Penciclovir Immunocompromised Study Group." Antimicrobial Agents Chemotherapy. 1999 May; 43(5):1192-7.

Sacks SL, Wilson B. "Famciclovir/penciclovir." Advances in Experimental Medical Biology. 1999; 458: 135-147.

Created: March 1st, 2000
Updated: March 5th, 2000