Penciclovir (Denavir)
Denavir®
Classification:
Antiinfective Agents
Dermatological Agents
Dermatological Agents
Description: Penciclovir, the active metabolite of the oral product famciclovir, is marketed as a topical agent for the treatment of herpes labialis. Penciclovir (Denavir®) is available in a non-greasy cream formulation for use on the lips and face. It is the first antiviral drug approved for the treatment of herpes labialis in the US. When penciclovir therapy is initiated within 1 hour of the signs or symptoms of herpes labialis, mean lesion duration is about 0.7-1 day shorter than without treatment. The more favorable results observed with topical penciclovir versus topical acyclovir for the treatment of herpes labialis may be due to the longer intracellular half-life of penciclovir in HSV-infected cells. Penciclovir was approved for the treatment of herpes labialis on September 24, 1996. It is currently a prescription-only product, but the manufacturer is expecting a transition to OTC status. In the UK, penciclovir cream is available as “Vectavir”.
Mechanism of Action: Penciclovir has in vitro 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 10-20 hours, compared with 0.7-1 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 cells not infected with HSV, DNA synthesis is unaltered. Resistant mutants of HSV can occur from qualitative changes in viral thymidine kinase or DNA polymerase. The most commonly encountered acyclovir-resistant mutants that are deficient in viral thymidine kinase are also resistant to penciclovir.
Pharmacokinetics: Penciclovir cream is applied topically to the lips or face. Application to mucous membranes is not recommended. 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). The systemic absorption of penciclovir following topical administration has not been evaluated in patients < 18 years of age.
References
1761. Spruance SL, Rea TL, Thoming C et al. Penciclovir cream for the treatment of herpes simplex labialis. JAMA 1997;277:1374-9.
[ Revised 10/29/2003 4:06:00 PM ]
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