Famciclovir: An overview
- Kimon C Zachary, MD
Kimon C Zachary, MD
- Assistant Professor of Medicine
- Harvard Medical School
Famciclovir is an oral prodrug which is converted by first-pass metabolism to the antiviral drug penciclovir [1,2].
MECHANISM OF ACTION
Penciclovir, upon intracellular uptake, is monophosphorylated by virally-encoded thymidine kinase and, subsequently, converted to a triphosphate by cellular enzymes. Penciclovir triphosphate preferentially inhibits the DNA polymerase of susceptible viruses; at clinically relevant levels, there is no substantial effect upon cellular DNA polymerase, thereby minimizing side effects to the host .
This mechanism is similar to that described for acyclovir; however, compared to acyclovir triphosphate, penciclovir triphosphate has a lower affinity for viral DNA polymerase but a longer intracellular half-life . (See "Acyclovir: An overview".)
Spectrum of activity — Penciclovir is active against herpes simplex virus (HSV) types 1 and 2, and varicella-zoster virus (VZV). Epstein-Barr virus is also susceptible in vitro .
Mechanism of resistance — The mechanisms of resistance to penciclovir are similar to those described for acyclovir . Three mechanisms have been shown to endow herpes simplex viruses with resistance to acyclovir, a phenomenon rare in the immunocompetent host :
- Famvir (famciclovir) prescribing information. SmithKline Beecham, 1997.
- Perry CM, Wagstaff AJ. Famciclovir. A review of its pharmacological properties and therapeutic efficacy in herpesvirus infections. Drugs 1995; 50:396.
- Drugs for non-HIV viral infections. Treat Guidel Med Lett 2007; 5:59.
- Chatis PA, Crumpacker CS. Resistance of herpesviruses to antiviral drugs. Antimicrob Agents Chemother 1992; 36:1589.
- Boyd MR, Safrin S, Kern ER. Penciclovir: A review of its spectrum of activity, selectivity, and cross-resistance pattern. Antiviral Chem Chemother 1993; 4(Suppl 1):3.
- Safrin S, Phan L. In vitro activity of penciclovir against clinical isolates of acyclovir-resistant and foscarnet-resistant herpes simplex virus. Antimicrob Agents Chemother 1993; 37:2241.
- Vere Hodge RA. Famciclovir and penciclovir: The mode of action of famciclovir including its conversion to penciclovir. Antiviral Chem Chemother 1993; 4:67.
- Saltzman R, Jurewicz R, Boon R. Safety of famciclovir in patients with herpes zoster and genital herpes. Antimicrob Agents Chemother 1994; 38:2454.
- Tyring S, Barbarash RA, Nahlik JE, et al. Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group. Ann Intern Med 1995; 123:89.
- Boon RJ, Griffin DR. Efficacy of famciclovir in the treatment of herpes zoster: reduction of pain associated with zoster. Neurology 1995; 45:S76.
- Loveless M, Sacks SL, Harris JRW. Famciclovir in the management of first-episode genital herpes. IDCP 1997; 6:S12.
- Sacks SL, Aoki FY, Diaz-Mitoma F, et al. Patient-initiated, twice-daily oral famciclovir for early recurrent genital herpes. A randomized, double-blind multicenter trial. Canadian Famciclovir Study Group. JAMA 1996; 276:44.
- Sacks SL. Management of recurrent genital herpes — episodic therapy with famciclovir. IDCP 1997; 6:S5.
- Frechette, G, Romanowski, B. Efficacy and safety of famciclovir for the treatment of HSV infection in HIV+ patients. Can J Infect Dis 1997; 8:44A.
- Schacker T, Hu HL, Koelle DM, et al. Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial. Ann Intern Med 1998; 128:21.