Three oral antiviral medications are used to treat herpes: acyclovir, valacyclovir, and famciclovir. All three work against both HSV-1 (which typically causes cold sores) and HSV-2 (which typically causes genital herpes). None of these drugs cure herpes, but they shorten outbreaks, reduce their severity, and can be taken daily to prevent recurrences.
The Three Core Antiviral Medications
Acyclovir is the oldest of the three and has been in use since the 1980s. It works by mimicking a building block of DNA. When the herpes virus tries to copy itself, it incorporates the drug instead of the real building block, which stops viral replication in its tracks. Valacyclovir and famciclovir are newer medications that work through the same basic mechanism but are absorbed more efficiently by your body, meaning you can take fewer pills per day.
In practice, valacyclovir is the most commonly prescribed of the three because of its convenient dosing. For a first genital herpes outbreak, the CDC recommends taking it twice a day for 7 to 10 days. Acyclovir requires three doses a day for the same duration, and famciclovir also requires three daily doses. All three are equally effective at treating outbreaks, so the choice often comes down to cost, insurance coverage, and how many pills you’re comfortable taking.
Treatment for a First Outbreak
A first herpes outbreak is usually the most painful and longest lasting, so treatment is recommended for everyone regardless of symptom severity. The standard course lasts 7 to 10 days, and it can be extended if sores haven’t fully healed by day 10. Starting medication as early as possible after symptoms appear makes the biggest difference. If you notice tingling, burning, or the first signs of blisters, that’s the ideal time to begin treatment.
Two Strategies for Recurring Outbreaks
After the first episode, herpes management splits into two approaches: episodic therapy and suppressive therapy. Which one makes sense depends on how often you get outbreaks and how much they affect your daily life.
Episodic Therapy
Episodic therapy means keeping medication on hand and taking it only when you feel an outbreak coming on. The courses are shorter than first-outbreak treatment. Valacyclovir can be taken twice daily for just 3 days, or once daily for 5 days. Famciclovir offers the shortest option: a single day of treatment at higher doses. Acyclovir courses run 2 to 5 days depending on the dose. The key is starting as soon as you notice prodromal symptoms like tingling, itching, or localized pain, ideally within the first 24 hours.
Suppressive Therapy
Suppressive therapy means taking a lower dose of antiviral medication every single day, whether or not you’re having an outbreak. This approach is typically recommended for people who experience six or more outbreaks per year, though anyone who wants fewer outbreaks or less anxiety about transmission can consider it. Valacyclovir can be taken as little as once a day for suppression. Acyclovir requires twice-daily dosing, and famciclovir also requires twice-daily dosing.
Daily suppressive therapy does more than just prevent visible outbreaks. A study in Open Forum Infectious Diseases found that daily valacyclovir reduced genital viral shedding by 94%, dropping shedding from about 9.7% of days to just 0.05% of days. Since viral shedding is what allows herpes to spread to a partner (even when no sores are visible), this reduction meaningfully lowers transmission risk. Suppressive therapy can be taken indefinitely, and many people stay on it for years without issues.
Topical Treatments
For oral herpes (cold sores), topical creams are available both over the counter and by prescription. Docosanol (sold as Abreva) is the main over-the-counter option. Prescription topical options include penciclovir cream and acyclovir cream. In comparative studies, penciclovir cream has shown the best performance among the three topicals at reducing lesion size and viral levels.
Topical treatments are generally less effective than oral antivirals. They can shorten a cold sore by roughly a day, while oral medications tend to have a larger impact on healing time and symptom severity. For genital herpes, topical treatments are not recommended as a primary approach. If you’re dealing with frequent or severe cold sores, oral antivirals are the more effective choice even for HSV-1.
Side Effects and Tolerability
All three oral antivirals are well tolerated by most people. The most common side effects are mild: nausea, diarrhea, headache, and general fatigue. These tend to be temporary and often resolve within the first few days of treatment.
Serious side effects are rare but worth knowing about. In uncommon cases, acyclovir can affect kidney function, particularly in people who are already dehydrated or have pre-existing kidney problems. Staying well hydrated while taking any of these medications helps protect your kidneys. Signs of a more serious reaction include decreased urination, unusual bruising or bleeding, confusion, or swelling in the legs and feet. Allergic reactions (hives, difficulty breathing, facial swelling) are possible but very uncommon.
People with kidney disease may need adjusted doses, since all three drugs are cleared through the kidneys. Otherwise, there are no major drug interactions that affect most people, though it’s worth mentioning all your current medications when getting a prescription.
Herpes Treatment During Pregnancy
Pregnant women with a history of genital herpes are typically started on suppressive antiviral therapy at 36 weeks of gestation. The goal is to prevent an active outbreak at the time of delivery, since herpes can be transmitted to the baby during vaginal birth. Acyclovir and valacyclovir are both used during pregnancy and have extensive safety data in this population. Famciclovir is generally avoided during pregnancy due to less available safety information.
When Standard Medications Don’t Work
Antiviral resistance is uncommon in people with healthy immune systems, but it can occur in immunocompromised individuals, such as those with HIV or organ transplant recipients on immunosuppressive drugs. When herpes doesn’t respond to standard antivirals, foscarnet is the primary alternative. It works through a different mechanism, targeting the viral copying machinery at a different point, and is given intravenously in a hospital setting.
A newer drug called pritelivir is also in development specifically for immunocompromised patients with treatment-resistant herpes. It works by a completely different mechanism than current antivirals, blocking the virus’s ability to unwind its DNA before copying. It is currently available only through expanded access programs for patients who have no other treatment options.