Anti-Herpes Simplex Virus and Varicella-Zoster Virus Agents

Agents: acyclovir, valacyclovir, famciclovir

These agents are primarily used in the treatment of infections caused by herpes simplex virus (HSV) and varicella-zoster virus (VZV), though they are active against some other viruses as well. All of these agents are nucleoside analogs that prevent viral DNA replication. Acyclovir is poorly absorbed and must be given up to 5 times daily when administered orally; valacyclovir and famciclovir are pro-drugs that are absorbed better and can be administered less frequently. Only acyclovir can be administered intravenously, and it is the agent of choice for serious HSV infections such as encephalitis.

Spectrum

Good: HSV-1 and HSV-2

Moderate: VZV

Poor: Epstein-Barr virus (EBV), cytomegalovirus  (CMV), HIV

Adverse Effects

These drugs are generally well tolerated with few ad-verse effects. The most concerning adverse effect is nephrotoxicity through either crystallization or AIN,  most commonly associated with IV acyclovir in higher doses. Crystallization is preventable through hydra-tion and correct dosing in renally impaired patients.  Seizures, tremors, or other CNS effects can also occur. Nausea, diarrhea, and rash are more common.  Thrombotic thrombocytopenic purpura has been re-ported with valacyclovir in HIV patients.

Important Facts

• Valacyclovir is a pro-drug of acyclovir with substantially improved bioavailability and less-frequent dosing. Its disadvantage is higher cost. Famciclovir is a pro-drug of penciclovir, an agent that is available only as a topical preparation.

• Acyclovir dosing varies widely by indication and host status. Be sure to double-check that it is appropriate for your patients.

• Acyclovir is most nephrotoxic in combination with diuretics or other nephrotoxins. Keep your patients hydrated during acyclovir therapy,  particularly if it is given in higher IV doses.

What They’re Good For

Acyclovir is the drug of choice for severe or difficult-to-treat HSV infections, such as encephalitis or severe HSV outbreaks among HIV patients. Any of these agents can be used to treat HSV-2 infections  (genital herpes) to prevent outbreaks or decrease symptom duration. They are all also effective in treating VZV infection.

Don’t Forget!

Make sure your patient can afford valacyclovir or famciclovir before prescribing either one. Oral acyclovir is less convenient, but much less expensive.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.