Herpes Simplex Medication

Updated: May 24, 2021
  • Author: Folusakin O Ayoade, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Medication Summary

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



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. Only topical preparations available, and they are well suited for herpes labialis (cold sores).

Acyclovir (Zovirax)

Synthetic purine nucleoside analogue with activity against a number of herpes viruses, 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 by intestinal and hepatic metabolism. Better absorbed than acyclovir and more expensive but has a more convenient dosing regimen.

Famciclovir (Famvir)

Prodrug that when biotransformed into active metabolite, penciclovir, may inhibit viral DNA synthesis/replication. Similarly to valacyclovir but has better bioavailability than acyclovir. Used against herpes simplex and varicella-zoster viruses.


Viral helicase-primase inhibitor

Pritelivir and Amenamivir

Pritelivir has potent anti-viral activity against HSV 1 &2. It does not require phosphorylation by thymidine kinase, and therefore active against viruses that are resistant to acyclovir and penciclovir because of thymidine kinase deficiencies.  Pritelivir is being developed for the treatment of acyclovir-resistant and dual-resistant (resistant to acyclovir and intolerant or resistant to foscarnet) mucocutaneous infections in immune-compromised patients. Use of pritelivir compared with valacyclovir resulted in a lower percentage of swabs with HSV detection over 28 days. (Wald A, Timmler B, Magaret A, et al. Effect of Pritelivir Compared With Valacyclovir on Genital HSV-2 Shedding in Patients With Frequent Recurrences: A Randomized Clinical Trial. JAMA. 2016;316(23):2495–2503. doi:10.1001/jama.2016.18189). 

To date, therapy has been limited to the short-term treatment of genital herpetic infections as opposed to long-term suppressive therapy. Further long-term toxicity studies are in progress to determine acceptability of long-term suppressive administration. (PMID: 30443341)