eMedicine Specialties > Infectious Diseases > Viral Infections

Herpes Simplex: Treatment & Medication

Author: Michelle R Salvaggio, MD, Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, University of Oklahoma Health Sciences Center
Coauthor(s): Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus; Meena Seenivasan, MD, Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn; Swati Kumar, MD, Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children's Specialty Group, Children's Hospital of Wisconsin
Contributor Information and Disclosures

Updated: May 27, 2009

Treatment

Medical Care

  • Overall, medical treatment of herpes simplex virus (HSV) infection is centered around specific antiviral treatment. While the same medications are active against HSV-1 and HSV-2, the location of the lesions and the chronicity (primary or reactivation) of the infection dictate the dosage and frequency of medication. It is important to note that life-threatening HSV infections in immunocompromised patients and HSV encephalitis require high-dose intravenous acyclovir, often started empirically.12
  • When constitutional effects such as fever occur, symptomatic treatment can be used.
  • Appropriate wound care is needed, and treatment for secondary bacterial skin infections may be required.

Consultations

  • Consultation with a dermatologist may be beneficial in cases of atypical lesions.
  • In immunocompromised patients with invasive HSV infection, consultation of specialty associated with the organ system affected should be sought early (eg, pulmonologist for possible HSV pneumonitis) in order to aid in diagnosis.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antivirals

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.

Adult

Apply q2h while awake for 4 d at first sign of symptom; for oral-facial HSV only

Pediatric

Administer as in adults

Documented hypersensitivity; previous adverse reaction to famciclovir

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

May experience mild erythema


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).

Adult

First episode mucocutaneous herpes simplex: 200 mg PO 5 times daily or 400 mg tid for 7-10 d or until clinical resolution occurs
Recurrent genital herpes: 200 mg PO five times daily for 5 d
Chronic suppressive therapy: 400 mg bid or 200 mg 3-5 times daily; reevaluate after 1 y
Herpes simplex encephalitis: 10 mg/kg IV q8h for 10-14 d
Severe infection in immunocompromised host: 5-10 mg/kg IV q8h for 5-10 d

Pediatric

First episode mucocutaneous herpes simplex: 20-30 mg/kg/d in 5 divided doses for 7-10 d
Severe infections in immunocompromised children: 10 mg/kg/d IV q8h for 7 d
Herpes encephalitis: 20 mg/kg IV q8h for 10-14 d

Concomitant use of probenecid or zidovudine prolongs half-life and increases CNS toxicity

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Renal dysfunction (usually reversible) can occur during high-dose IV administration (primarily related to drug crystalluria); effect can be minimized by slow infusion and adequate hydration; neurological symptoms, including lethargy, agitation, myoclonus, or seizures is observed in <1% of patients; appears to be dose-related phenomenon with increased risk with azotemia


Valacyclovir (Valtrex)

Prodrug rapidly converted to the active drug acyclovir. More expensive but has a more convenient dosing regimen than acyclovir.

Adult

First episode herpes simplex: 1 g bid for 10 d, preferably beginning within 48 h of onset
Recurrent episode herpes simplex: 500 mg bid for 5 d beginning within 24 h of onset
Suppressive dosing for HSV: 500 mg to 1 g/d

Pediatric

Not established

Probenecid, zidovudine, or cimetidine coadministration prolongs half-life and increases CNS toxicity of valacyclovir

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure and coadministration of nephrotoxic drugs; associated with onset of hemolytic uremic syndrome


Famciclovir (Famvir)

Prodrug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. Used against herpes simplex and varicella-zoster viruses.

Adult

Recurrent genital HSV: 125 mg PO bid for 5 d
Recurrent genital HSV in HIV-infected patients: 500 mg PO bid for 7 d
Suppression of frequent recurrence of genital HSV: 250 mg PO bid up to 12 mo

Pediatric

Not established

Coadministration of probenecid or cimetidine may increase toxicity; coadministration increases bioavailability of digoxin

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in renal failure or coadministration of nephrotoxic drugs; dosage adjustment in renal impairment recommended (half-life prolonged by 5-6 times if CrCl <20 mL/min)

More on Herpes Simplex

Overview: Herpes Simplex
Differential Diagnoses & Workup: Herpes Simplex
Treatment & Medication: Herpes Simplex
Follow-up: Herpes Simplex
Multimedia: Herpes Simplex
References
Further Reading
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References

  1. 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.

  2. Kimberlin DW, Rouse DJ. Clinical practice. Genital herpes. N Engl J Med. May 6 2004;350(19):1970-7. [Medline].

  3. 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].

  4. 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].

  5. 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].

  6. 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].

  7. 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].

  8. 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].

  9. 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].

  10. 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].

  11. 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].

  12. 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.

  13. Green LK, Pavan-Langston D. Herpes simplex ocular inflammatory disease. Int Ophthalmol Clin. Spring 2006;46(2):27-37. [Medline].

  14. Whitley RJ. Herpes simplex virus infections of the central nervous system. A review. Am J Med. Aug 29 1988;85(2A):61-7. [Medline].

  15. 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].

  16. American College Obstetricians and Gynecologists. Management of herpes in pregnancy. ACOG Practice Bulletin. October 1999;Number 8:644-652.

  17. 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].

  18. 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].

  19. 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].

  20. [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].

  21. [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].

  22. [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].

  23. 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].

  24. 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].

  25. 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].

  26. 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].

  27. Eisenstein LE, Calio AJ, Cunha BA. Herpes simplex (HSV-1) aseptic meningitis. Heart Lung. May-Jun 2004;33(3):196-7. [Medline].

  28. 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].

  29. 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].

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Keywords

herpes simplex, HSV, herpes simplex type 1, HSV-1, herpes simplex type 2, HSV-2, oral herpes, genital herpes, HSV infection, Herpesviridae, Alphaherpesvirinae, encephalitis, primary herpes gingivostomatitis, acute herpetic gingivostomatitis, acute herpetic pharyngotonsillitis, herpes labialis, primary genital herpes, cervicitis, urethritis, herpetic proctitis, sacral neuralgia, neonatal herpes, primary mucocutaneous HSV infections, recurrent mucocutaneous HSV infection

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Contributor Information and Disclosures

Author

Michelle R Salvaggio, MD, Assistant Professor, Department of Internal Medicine, Section of Infectious Diseases, University of Oklahoma College of Medicine; Medical Director of Infectious Diseases Institute, University of Oklahoma Health Sciences Center
Michelle R Salvaggio, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Merck Honoraria Speaking and teaching

Coauthor(s)

Larry I Lutwick, MD, Professor of Medicine, State University of New York, Downstate Medical School; Director, Infectious Diseases, Veterans Affairs New York Harbor Health Care System, Brooklyn Campus
Larry I Lutwick, MD is a member of the following medical societies: American College of Physicians and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Meena Seenivasan, MD, Fellow, Department of Infectious Disease, State University of New York Health Science Center at Brooklyn
Disclosure: Nothing to disclose.

Swati Kumar, MD, Assistant Professor of Pediatrics, Division of Infectious Diseases, Medical College of Wisconsin, Consulting Staff, Children's Specialty Group, Children's Hospital of Wisconsin
Swati Kumar, MD is a member of the following medical societies: American Academy of Pediatrics, Infectious Diseases Society of America, and Pediatric Infectious Diseases Society
Disclosure: Nothing to disclose.

Medical Editor

Thomas J Marrie, MD, Chair, Professor, Department of Medicine, Division of Infectious Diseases, University of Alberta College of Medicine
Thomas J Marrie, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Society for Microbiology, Canadian Infectious Disease Society, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Charles V Sanders, MD, Edgar Hull Professor and Chairman, Department of Internal Medicine, Professor of Microbiology, Immunology and Parasitology, Louisiana State University School of Medicine at New Orleans; Medical Director, Medicine Hospital Center, Charity Hospital and Medical Center of Louisiana at New Orleans; Consulting Staff, Ochsner Medical Center
Charles V Sanders, MD is a member of the following medical societies: Alliance for the Prudent Use of Antibiotics, Alpha Omega Alpha, American Association for the Advancement of Science, American Association of University Professors, American Clinical and Climatological Association, American College of Physician Executives, American College of Physicians, American Federation for Medical Research, American Foundation for AIDS Research, American Geriatrics Society, American Lung Association, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Association for Professionals in Infection Control and Epidemiology, Association of American Medical Colleges, Association of American Physicians, Association of Professors of Medicine, Infectious Disease Society for Obstetrics and Gynecology, Infectious Diseases Society of America, Louisiana State Medical Society, Orleans Parish Medical Society, Royal Society of Medicine, Sigma Xi, Society of General Internal Medicine, Southeastern Clinical Club, Southern Medical Association, Southern Society for Clinical Investigation, and Southwestern Association of Clinical Microbiology
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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