Herpes is treated with three FDA-approved antiviral medications: acyclovir, valacyclovir, and famciclovir. All three are prescription pills that work by blocking the virus’s ability to copy itself inside your cells. They don’t cure herpes, but they shorten outbreaks, reduce symptoms, and can be taken daily to suppress future flare-ups. For oral herpes (cold sores), there’s also an over-the-counter cream called docosanol.
The Three Prescription Antivirals
Acyclovir is the oldest of the three and has been used since the 1980s. It works well but needs to be taken more frequently throughout the day. Valacyclovir is essentially an upgraded version of acyclovir. Your body converts it into acyclovir after you swallow it, but it’s absorbed more efficiently, so you can take it fewer times per day. Famciclovir is a separate drug with similarly strong absorption.
All three medications target the same weak point in the virus. When herpes reactivates and starts replicating, it relies on a specific enzyme to build new copies of its DNA. These antivirals slip into that process and act as decoys, jamming the enzyme so it can’t finish assembling new virus particles. Because they only activate inside infected cells, they leave healthy cells largely alone, which is why side effects tend to be mild.
Topical antiviral creams for genital herpes offer minimal benefit and are generally discouraged. The oral pills are far more effective.
Treatment for a First Outbreak
A first herpes outbreak is usually the most severe, and treatment lasts 7 to 10 days. The standard options are:
- Acyclovir: 400 mg three times a day
- Valacyclovir: 1,000 mg twice a day
- Famciclovir: 250 mg three times a day
Starting medication as early as possible matters. The sooner you begin treatment after symptoms appear, the more effectively the drug limits viral replication and shortens the outbreak. If you notice prodromal signs like tingling, burning, or itching in the area before sores develop, that’s the ideal time to start.
Episodic Therapy for Recurring Outbreaks
If you get occasional outbreaks but not frequently enough to justify daily medication, episodic therapy lets you keep pills on hand and take them only when a flare-up begins. Treatment courses are shorter than for a first episode, typically 1 to 5 days depending on the drug and dose.
Valacyclovir can be taken as 500 mg twice a day for 3 days, or 1,000 mg once daily for 5 days. Famciclovir offers one of the shortest regimens: 1,000 mg twice in a single day. Acyclovir requires 800 mg doses, taken either twice daily for 5 days or three times daily for 2 days. Your prescriber will help you choose based on what fits your routine and how often outbreaks occur.
The key to episodic therapy is speed. You need a prescription filled in advance so you can start at the first sign of tingling or discomfort, not after sores have already formed.
Daily Suppressive Therapy
For people who experience frequent outbreaks (generally six or more per year) or who want to reduce the risk of transmitting herpes to a partner, daily suppressive therapy is an option. You take a lower dose every day, whether or not you have symptoms. This keeps the virus quieter and reduces the frequency of outbreaks significantly. It also lowers viral shedding, which is the main way herpes spreads even when no visible sores are present.
The daily regimens are:
- Valacyclovir: 500 mg or 1,000 mg once a day
- Acyclovir: 400 mg twice a day
- Famciclovir: 250 mg twice a day
Valacyclovir’s once-daily dosing makes it the most popular choice for suppressive therapy. Many people stay on it for years. There’s no set time limit, though your prescriber may periodically reassess whether you still need it, since outbreak frequency often decreases naturally over time.
Over-the-Counter Options for Cold Sores
If you’re dealing with oral herpes (cold sores on or around the lips), docosanol is the main FDA-approved over-the-counter treatment. It’s sold as a cream under the brand name Abreva and works differently from prescription antivirals. Rather than targeting the virus’s replication machinery, it helps block the virus from entering healthy skin cells.
You apply docosanol to the affected area five times a day until the sore heals. It won’t cure the infection, but it can reduce pain and help sores heal somewhat faster. It’s most effective when applied at the very first tingle, before a blister forms. For more severe or frequent cold sore outbreaks, the same prescription antivirals used for genital herpes (valacyclovir, acyclovir, famciclovir) can also be prescribed for oral herpes.
Side Effects and Long-Term Safety
All three prescription antivirals are generally well tolerated. The most common side effects are mild: headache, nausea, and stomach discomfort. These usually improve after the first few days of treatment.
The most important safety consideration involves kidney function. Acyclovir (and by extension valacyclovir, which converts to acyclovir in your body) is cleared through the kidneys. In people with impaired kidney function, the drug can accumulate to higher-than-intended levels. When that happens, it can cross into the brain and cause neurological symptoms like confusion, lethargy, agitation, hallucinations, or in rare cases, seizures. These effects are generally reversible once the medication is stopped or the dose is adjusted.
For this reason, kidney function is typically checked before starting treatment, and doses are adjusted downward for anyone with reduced kidney function. Staying well hydrated while taking these medications helps your kidneys process the drug efficiently. For people with normal kidney function taking standard doses, long-term use has a strong safety record spanning decades.
How to Choose Between Them
All three antivirals are similarly effective. The differences come down to convenience, cost, and how many pills you’re willing to take each day. Valacyclovir requires the fewest doses, sometimes just once a day, which makes it the most commonly prescribed. Acyclovir is often the cheapest option since it’s been generic the longest, but it requires more frequent dosing. Famciclovir sits in the middle and offers some of the shortest episodic treatment courses.
Your prescriber will factor in your outbreak frequency, whether you want suppressive or episodic therapy, your kidney health, and insurance coverage. All three get the job done. The best one is the one you’ll actually take consistently.