Herpes Simplex Medication
- Author: Michelle R Salvaggio, MD, FACP; Chief Editor: Burke A Cunha, MD more...
Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications.
Antivirals
Class Summary
Nucleoside analogs are phosphorylated initially by viral thymidine kinase to eventually form a nucleoside triphosphate. These molecules inhibit herpes simplex virus (HSV) polymerase with 30-50 times the potency of human alpha-DNA polymerase.
Penciclovir (Denavir)
Inhibitor of DNA polymerase in HSV-1 and HSV-2 strains, inhibiting viral replication.
Acyclovir (Zovirax)
Synthetic purine nucleoside analogue with activity against a number of herpesviruses, including herpes simplex and varicella-zoster. Highly selective for virus-infected cells because of its high affinity for viral thymidine kinase enzyme. This effect serves to concentrate acyclovir monophosphate into virus-infected cells. The monophosphate then is metabolized into the triphosphate active form by cellular kinases.
Double dose is suggested for herpes simplex proctitis or ocular infections. Ocular infections also can be treated with topical acyclovir. Oral suspension available (40 mg/mL).
Valacyclovir (Valtrex)
Prodrug rapidly converted to the active drug acyclovir. More expensive but has a more convenient dosing regimen than acyclovir.
Famciclovir (Famvir)
Prodrug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. Used against herpes simplex and varicella-zoster viruses.
Corey L. Herpes Simplex Virus. In: Mandell Gl, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. Vol 2. 6th ed. Pennsylvania: Elsevier; 2005:1762-80.
Kimberlin DW, Rouse DJ. Clinical practice. Genital herpes. N Engl J Med. May 6 2004;350(19):1970-7. [Medline].
Mark KE, Wald A, Magaret AS, Selke S, Olin L, Huang ML. Rapidly cleared episodes of herpes simplex virus reactivation in immunocompetent adults. J Infect Dis. Oct 15 2008;198(8):1141-9. [Medline].
Fleming DT, McQuillan GM, Johnson RE, et al. Herpes simplex virus type 2 in the United States, 1976 to 1994. N Engl J Med. Oct 16 1997;337(16):1105-11. [Medline].
Arduino PG, Porter SR. Oral and perioral herpes simplex virus type 1 (HSV-1) infection: review of its management. Oral Dis. May 2006;12(3):254-70. [Medline].
Spruance SL, Overall JC Jr, Kern ER, Krueger GG, Pliam V, Miller W. The natural history of recurrent herpes simplex labialis: implications for antiviral therapy. N Engl J Med. Jul 14 1977;297(2):69-75. [Medline].
Corey L, Adams HG, Brown ZA, Holmes KK. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Ann Intern Med. Jun 1983;98(6):958-72. [Medline].
Wald A, Zeh J, Selke S, Ashley RL, Corey L. Virologic characteristics of subclinical and symptomatic genital herpes infections. N Engl J Med. Sep 21 1995;333(12):770-5. [Medline].
Benedetti JK, Zeh J, Corey L. Clinical reactivation of genital herpes simplex virus infection decreases in frequency over time. Ann Intern Med. Jul 6 1999;131(1):14-20. [Medline].
Sköldenberg B, Jeansson S, Wolontis S. Herpes simplex virus type 2 and acute aseptic meningitis. Clinical features of cases with isolation of herpes simplex virus from cerebrospinal fluids. Scand J Infect Dis. 1975;7(4):227-32. [Medline].
Aurelius E, Johansson B, Skoldenberg B, Staland A, Forsgren M. Rapid diagnosis of herpes simplex encephalitis by nested polymerase chain reaction assay of cerebrospinal fluid. Lancet. Jan 26 1991;337(8735):189-92. [Medline].
Gnann JW, Salvaggio MR. Drugs for Herpesvirus Infections. In: Cohen J, Powderly W, eds. Infectious Diseases. Vol 2. 2nd ed. New York: Mosby; 2004:1895-909.
Green LK, Pavan-Langston D. Herpes simplex ocular inflammatory disease. Int Ophthalmol Clin. Spring 2006;46(2):27-37. [Medline].
Whitley RJ. Herpes simplex virus infections of the central nervous system. A review. Am J Med. Aug 29 1988;85(2A):61-7. [Medline].
Gardella C, Brown ZA, Wald A, Morrow RA, Selke S, Krantz E. Poor correlation between genital lesions and detection of herpes simplex virus in women in labor. Obstet Gynecol. Aug 2005;106(2):268-74. [Medline].
American College Obstetricians and Gynecologists. Management of herpes in pregnancy. ACOG Practice Bulletin. October 1999;Number 8:644-652.
[Best Evidence] Pasternak B, Hviid A. Use of acyclovir, valacyclovir, and famciclovir in the first trimester of pregnancy and the risk of birth defects. JAMA. Aug 25 2010;304(8):859-66. [Medline].
Brown ZA, Wald A, Morrow RA, Selke S, Zeh J, Corey L. Effect of serologic status and cesarean delivery on transmission rates of herpes simplex virus from mother to infant. JAMA. Jan 8 2003;289(2):203-9. [Medline].
Corey L, Wald A, Celum CL, Quinn TC. The effects of herpes simplex virus-2 on HIV-1 acquisition and transmission: a review of two overlapping epidemics. J Acquir Immune Defic Syndr. Apr 15 2004;35(5):435-45. [Medline].
Nagot N, Ouedraogo A, Foulongne V, Konate I, Weiss HA, Vergne L. Reduction of HIV-1 RNA levels with therapy to suppress herpes simplex virus. N Engl J Med. Feb 22 2007;356(8):790-9. [Medline].
[Best Evidence] Baeten JM, Strick LB, Lucchetti A, Whittington WL, Sanchez J, Coombs RW, et al. Herpes simplex virus (HSV)-suppressive therapy decreases plasma and genital HIV-1 levels in HSV-2/HIV-1 coinfected women: a randomized, placebo-controlled, cross-over trial. J Infect Dis. Dec 15 2008;198(12):1804-8. [Medline].
[Best Evidence] Andrews WW, Kimberlin DF, Whitley R, Cliver S, Ramsey PS, Deeter R. Valacyclovir therapy to reduce recurrent genital herpes in pregnant women. Am J Obstet Gynecol. Mar 2006;194(3):774-81. [Medline].
[Best Evidence] Sheffield JS, Hill JB, Hollier LM, Laibl VR, Roberts SW, Sanchez PJ. Valacyclovir prophylaxis to prevent recurrent herpes at delivery: a randomized clinical trial. Obstet Gynecol. Jul 2006;108(1):141-7. [Medline].
Hasegawa T, Kawana T, Okuda T, Horii M, Tsukada T, Shiraki K. Susceptibility to acyclovir of herpes simplex virus isolates obtained between 1977 and 1996 in Japan. J Med Virol. Jan 2001;63(1):57-63. [Medline].
Rabella N, Otegui M, Labeaga R, et al. Antiviral susceptibility of Herpes simplex viruses and its clinical correlates: a single center's experience. Clin Infect Dis. Apr 15 2002;34(8):1055-60. [Medline].
Cunha BA, Eisenstein LE, Dillard T, Krol V. Herpes simplex virus (HSV) pneumonia in a heart transplant: diagnosis and therapy. Heart Lung. Jan-Feb 2007;36(1):72-8. [Medline].
Cunha BA, Fatehpuria R, Eisenstein LE. Listeria monocytogenes encephalitis mimicking Herpes Simplex virus encephalitis: the differential diagnostic importance of cerebrospinal fluid lactic acid levels. Heart Lung. May-Jun 2007;36(3):226-31. [Medline].
Eisenstein LE, Calio AJ, Cunha BA. Herpes simplex (HSV-1) aseptic meningitis. Heart Lung. May-Jun 2004;33(3):196-7. [Medline].
Eisenstein LE, Cunha BA. Herpes simplex virus pneumonia presenting as failure to wean from a ventilator. Heart Lung. Jan-Feb 2003;32(1):65-6. [Medline].
Mohan S, Hamid NS, Cunha BA. A cluster of nosocomial herpes simplex virus type 1 pneumonia in a medical intensive care unit. Infect Control Hosp Epidemiol. Nov 2006;27(11):1255-7. [Medline].
Johnston C, et al. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomized, open-label, cross-over trials [published online ahead of print January 5, 2012]. Lancet. doi:10.1016/S0140-6736(11)61750-9.
Belshe RB, et al. Efficacy Results of a trial of a herpes simplex vaccine. N Engl J Med. 2012;366:34-43.

