The major drugs developed to work against herpes simplex virus (HSV) are antiviral agents called nucleosides and nucleotide analogues, which block viral reproduction. They include acyclovir (Zovirax), valacyclovir (Valtrex), famciclovir (Famvir).

The antiviral medications available in pill form have been specifically developed for the treatment of genital herpes. Antiviral medications may significantly lessen the severity of a primary outbreak and reduce the time it takes genital herpes outbreaks to heal. The medication also decreases the number of days of painful symptoms and for some people, the number of days you can spread the virus. Antiviral medication is most effective if it is taken when you first notice the prodromal symptoms (tingling and pain) of a recurrent genital herpes outbreak and if they are taken for the next 5 to 7 days or until symptoms go away. Some people with frequent recurrent outbreaks (more than 6 recurrences a year) take antiviral medication every day (suppressive therapy) to help reduce the frequency and duration of recurrent outbreaks.

Brief History

Acyclovir (brand name Zovirax) is the oldest of the antiviral medications. It has been available since 1982 in a topical form (as an ointment) and sold since 1985 in pill form. Now acyclovir is available in a generic form.

Valtrex (valacyclovir) was the second antiviral medication to come to market in the United States, and it was approved by the FDA in December 15, 1995. Valtrex is manufactured by GlaxoSmithKline. Valtrex is a prodrug of acyclovir, meaning that the body converts it to acyclovir after it has been absorbed. This medication delivers acyclovir more efficiently so that the body absorbs much of the drug, which has the advantage of taking the medication fewer times during the day.

Famvir (famciclovir) is a prodrug manufactured by Novartis. When taken, the body converts it to the long-acting antiviral drug penciclovir. Like valacyclovir, it is well absorbed, persists for a longer time in the body, and can be taken less frequently than acyclovir.

Mechanism of action

Antiviral agents reduce viral replication by inhibiting viral DNA synthesis, needed to reproduce itself. This helps to keep the virus inactive.

Approved indications and uses

Acyclovir is indicated for:

• treatment of initial episodes and the management of recurrent episodes of genital herpes

• treatment of acute herpes zoster (shingles)

• treatment of chickenpox (varicella)

Valacyclovir is indicated for:

• treatment or suppression of genital herpes and for the suppression of recurrent genital herpes

• reduction of transmission of genital herpes

• treatment of herpes zoster

• treatment of cold sores (herpes labialis)

Famciclovir is indicated for:

• treatment or suppression of recurrent genital herpes

• treatment of acute herpes zoster

Efficacy

Clinical studies have not found any significant differences in effectiveness among the three medications. All are quite safe, very rarely producing any side effects at all. For the treatment of first genital herpes infections, oral acyclovir or valacyclovir is preferable to famciclovir. The efficacy of famciclovir for initial episode genital herpes infection has not been established.

Intravenous acyclovir is used to treat serious flare-ups or outbreaks that effect internal organs.

Adverse reactions and side effects

All these agents are well tolerated and have excellent safety records. Possible side effects from oral agents include nausea, vomiting, headache, fatigue, tremor, and very rarely, seizures. They can effect the kidney, however, and people with kidney problems should use them with caution and at lower doses. Intravenous administration increases the risk for kidney problems and can cause blood clots at the injection site. In rare cases, it can cause central nervous system complications.

Pharmacokinetics

Acyclovir has poor bioavailability of about 20% and a short half-life, which necessitates frequent dosing. Acyclovir speeds healing of lesions and suppress viral shedding if taken within 24 hours of the first indication of a recurrent episode. Early treatment may even prevent the development of lesions in some patients.

Valacyclovir provides a unique mechanism of enhancing the oral bioavailability of the parent compound, acyclovir. Valacyclovir is a prodrug converted to acyclovir in the intestine and liver. It has better bioavailability (about 55%) and has a longer duration of action than acyclovir. Thus, valacyclovir requires less frequent dosing than acyclovir. Valacyclovir is most effective if taken within 24 hours of the first signs of an outbreak.

Famciclovir is a prodrug for the active metabolite penciclovir. Famciclovir is converted into its active compound within the infected cell by contact with an enzyme from the virus. It has high bioavailability of 77%. It remains active in the body longer than acyclovir (half the dose is still active after 10 to 20 hours) and, like valacyclovir, requires less frequent dosing (usually two or three times a day). It is most effective if taken within six hours of onset of symptoms.

Both Famciclovir and valacyclovir have greater oral bioavailability that acyclovir. Famciclovir and valacyclovir, which are better absorbed by the body, can be taken less often than acyclovir. The simpler dosing schedule of famciclovir and valacyclovir, allows patients more convenient dosing regimens with less interruption of their activities of daily living.