Famciclovir and Penciclovir
Famciclovir (Famvir) is the diacetyl ester prodrug of
the acyclic guanosine analogue 6-deoxypenciclovir (Dena-vir). Penciclovir has activity against HSV-1, HSV-2, VZV, and HBV. After oral
administration, famciclovir is converted to penciclovir by first-pass
metabolism. Penciclovir has a mechanism of action similar to that of acyclovir.
It is first monophosphorylated by viral thymi-dine kinase; then it is converted
to a triphosphate by cellular kinases. Penciclovir triphosphate acts as a
com-petitive inhibitor of viral DNA polymerase, but unlike acyclovir, it does
not cause chain termination.
Mutations in DNA polymerase
or thymidine kinase may result in resistance. Acyclovir-resistant HSV strains that
exhibit thymidine kinase deficiency are also resistant to famciclovir and
Penciclovir is available as a
topical cream; its absorption through the skin is undetectable. Famciclovir is
well absorbed following oral administration and is rapidly converted to
penciclovir by hepatic first-pass metabo-lism. The bioavailability of
penciclovir following oral famciclovir administration is approximately 77%.
Penciclovir is less than 20% bound to plasma proteins.
The plasma elimination
half-life for penciclovir is 2 to 3 hours; however, the intracellular half-life
of penci-clovir triphosphate is 7 to 20 hours in infected cells. Most
penciclovir is eliminated unchanged by the kidney via glomerular filtration and
active tubular secretion. The plasma half-life is increased in individuals with
Penciclovir is approved as a
topical formulation for the treatment of herpes labialis. In immunocompetent
indi-viduals, penciclovir shortens the duration of lesion pres-ence and pain by
approximately half a day when it is ini-tiated within an hour of lesion
development and applied every 2 hours during waking hours for 4 days.
Famciclovir is indicated for
the treatment of acute herpes zoster (shingles); it is at least as effective in
re-ducing pain and healing time. Famciclovir is generally as effective as
acyclovir in the treatment of HSV. In im-munocompetent patients, famciclovir is
approved for the treatment and prophylaxis of recurrent genital her-pes. For
HIV-infected individuals, famciclovir is ap-proved for the treatment of all
recurrent mucocuta-neous HSV infections.
No significant adverse
effects to topical penciclovir have been reported. Oral famciclovir is
generally well tolerated. Adverse effects include headache, nausea, and
diarrhea. Confusion may occur, particularly in the elderly. Hallucinations and
urticaria have been re-ported. Animal studies have indicated that chronic
fam-ciclovir administration may be tumorigenic and impair spermatogenesis.
Dosage adjustment is necessary in in-dividuals with renal impairment.
Famciclovir may interact with
probenecid or other drugs eliminated by renal tubular secretion. This
inter-action may result in increased blood levels of penci-clovir or other