Acyclovir and valacyclovir are prescription antivirals that treat cold sores, genital herpes and shingles. Valacyclovir (brand name Valtrex) is a prodrug: your body converts it into acyclovir. Because valacyclovir is absorbed about 3 to 5 times better (roughly 55% vs 10–20%), it is taken once or twice a day instead of 2 to 5 times. Both work equally well when taken as prescribed; valacyclovir is more convenient, acyclovir is usually cheaper.
| Acyclovir | Valacyclovir | |
|---|---|---|
| Brand names | Zovirax, Sitavig | Valtrex |
| How it works | Active antiviral | Converted to acyclovir in the body |
| Oral absorption | About 10–20% | About 55% |
| Typical doses per day | 2–5 | 1–3 |
| Forms | Tablet, capsule, liquid, cream, ointment, buccal tablet, IV | Tablet only |
If you have been prescribed one and wondered whether the other would suit you better, the honest answer is that it depends less on which drug is “better” and more on your condition, your budget and how many doses a day you will realistically take. This guide compares the two side by side, condition by condition, so you can have a clearer conversation with your doctor or pharmacist.
What are acyclovir and valacyclovir?
Acyclovir and valacyclovir are nucleoside antivirals used against two members of the herpes virus family: herpes simplex virus (HSV-1 and HSV-2) and varicella-zoster virus, which causes chickenpox and shingles. They block the enzyme the virus uses to copy its DNA, so new virus particles stop forming.
Neither drug cures herpes. The virus stays dormant in nerve cells between outbreaks. What these medicines do is shorten an outbreak, ease pain, speed healing and, when taken daily, reduce how often outbreaks come back.
What is acyclovir?
Acyclovir was the first drug in this class, approved in the US in 1982, and it remains a widely used, low-cost generic. Its main limitation is absorption: only about 10–20% of an oral dose reaches the bloodstream, which is why it is taken several times a day.
Acyclovir comes in more forms than any other herpes antiviral:
- 400 mg and 800 mg tablets, and 200 mg capsules
- Oral suspension (liquid), useful for children and anyone who cannot swallow tablets
- 5% cream and ointment for skin and lip lesions
- A buccal tablet (Sitavig) that dissolves against the gum for cold sores
- Intravenous infusion for severe infections treated in hospital
What is valacyclovir?
Valacyclovir is a prodrug of acyclovir. Chemically it is acyclovir with an amino acid (L-valine) attached, which lets it ride a transporter in the gut. Once absorbed, enzymes in the gut wall and liver strip off the valine and release acyclovir.
The result is that about 55% of a valacyclovir dose reaches the blood as acyclovir, three to five times more than with oral acyclovir. Valacyclovir is available only as 500 mg and 1 g tablets.
Valtrex vs acyclovir: brand vs generic
Valtrex is the brand name for valacyclovir, and Zovirax is the original brand name for acyclovir. When people search “Valtrex vs acyclovir”, they are really comparing valacyclovir with acyclovir.
Generic versions of both contain the same active ingredient as the brands and must meet the same standards for strength, purity and absorption. Most people take the generic of either drug.
Key differences between acyclovir and valacyclovir
The active antiviral is the same; what differs is how well each is absorbed, how often you take it, the forms it comes in and what it costs. Whether you search “acyclovir vs valacyclovir” or “valacyclovir vs acyclovir”, the table below is the short version.
| Feature | Acyclovir | Valacyclovir |
|---|---|---|
| Drug type | Active antiviral | Prodrug, converted to acyclovir |
| Oral bioavailability | About 10–20% | About 55% |
| Doses per day (typical) | 2–5 | 1–3 |
| Forms | Tablet, capsule, liquid, cream, ointment, buccal tablet, IV | Tablet only (500 mg, 1 g) |
| Half-life of active drug | About 2.5–3.3 hours | About 2.5–3.3 hours (as acyclovir) |
| Use in children | Tablets and liquid from age 2 for chickenpox | Cold sores from age 12; chickenpox ages 2–17 |
| FDA-approved to reduce partner transmission | No | Yes (genital herpes) |
| Cost | Usually lower | Usually higher |
| Prescription needed | Yes (oral) | Yes |
What “bioavailability” means for you: it is the share of each dose that actually reaches your blood. Because more of each valacyclovir tablet gets through, you need fewer tablets to reach the same antiviral level, which is why a valacyclovir course often means two doses a day where acyclovir needs three to five.
Is valacyclovir better than acyclovir?
Valacyclovir is not more effective than acyclovir at healing an outbreak, but it is easier to take. In head-to-head trials, the two drugs produce similar healing times and symptom relief when each is taken at its recommended dose. The practical advantage of valacyclovir is fewer doses, which makes it easier to finish a course and to stay on daily suppression.
Which is stronger, acyclovir or valacyclovir?
Neither is “stronger” in the sense of being a more powerful antiviral, because both work as acyclovir inside the body. Valacyclovir simply delivers more acyclovir to the bloodstream per tablet.
That is also why you cannot compare milligram numbers directly. A 1 g valacyclovir tablet is not “stronger” than an 800 mg acyclovir tablet in any simple way; each dose is set so that the blood levels it produces are effective for the condition being treated.
What the trials show
- Genital herpes (first episode): a large international double-blind trial (Fife et al., 1997) compared valacyclovir 1 g twice daily with acyclovir 200 mg five times daily for 10 days. Healing time, pain and viral shedding were similar in both groups.
- Shingles: in a trial of adults aged 50 and over (Beutner et al., 1995), valacyclovir 1 g three times daily for 7 days healed the rash as well as acyclovir 800 mg five times daily, and shortened the duration of shingles-related nerve pain.
- Recurrent genital herpes and cold sores: short valacyclovir courses (one to three days) work as well as longer acyclovir courses, which is a convenience gain rather than a strength gain.
When acyclovir is the better choice
Acyclovir still makes more sense in several situations:
- Cost: generic acyclovir is usually the cheaper option, especially for long-term suppression.
- Children or swallowing problems: acyclovir is available as a liquid; valacyclovir is not commercially available as one.
- Topical treatment: acyclovir cream or ointment can be applied directly to a cold sore.
- Hospital care: severe infections, such as herpes encephalitis, are treated with intravenous acyclovir.
- Long track record: acyclovir has been used for more than 40 years, including widely in pregnancy.
Acyclovir vs valacyclovir by condition
Both drugs treat the same conditions, but the dose and length of treatment differ for each one. The tables below show standard adult doses for people with normal kidney function. They are for reference only: your prescriber sets your dose, and it may differ if you have kidney disease, a weakened immune system or are pregnant.
Valacyclovir vs acyclovir for cold sores
For cold sores (herpes labialis), valacyclovir’s one-day course is its biggest advantage. Treatment works best when started at the very first tingle, before a blister appears.
| Acyclovir | Valacyclovir | |
|---|---|---|
| Oral dose | 400 mg five times a day for 5 days (off-label use) | 2 g twice a day, 12 hours apart, for 1 day |
| Other options | 5% cream five times a day for 4 days; 50 mg buccal tablet once | None (tablet only) |
| Approved ages | Cream from age 12 | From age 12 |
Source: FDA prescribing information for valacyclovir and acyclovir topical products.
Acyclovir vs valacyclovir for genital herpes
For genital herpes, both drugs are first-line options in the CDC’s treatment guidelines, and they work equally well. Valacyclovir needs fewer doses per day and shorter courses for repeat outbreaks.
| Episode | Acyclovir | Valacyclovir |
|---|---|---|
| First outbreak | 400 mg three times a day for 7–10 days | 1 g twice a day for 7–10 days |
| Recurrent outbreak | 800 mg twice a day for 5 days, or 800 mg three times a day for 2 days | 500 mg twice a day for 3 days, or 1 g once a day for 5 days |
Source: CDC Sexually Transmitted Infections Treatment Guidelines, 2021.
Treatment of a recurrence works best if started within a day of symptoms appearing. Neither drug, taken only during outbreaks, stops you passing the virus to a partner; condoms and daily suppressive therapy reduce that risk.
Valacyclovir vs acyclovir for shingles
For shingles (herpes zoster), valacyclovir is often preferred because it means three doses a day instead of five and, in trials, shortened the duration of nerve pain. Start treatment within 72 hours of the rash appearing.
| Acyclovir | Valacyclovir | |
|---|---|---|
| Dose | 800 mg five times a day | 1 g three times a day |
| Duration | 7–10 days | 7 days |
Source: FDA prescribing information for acyclovir and valacyclovir.
Antivirals treat an active shingles episode; they do not prevent future ones. For prevention, adults aged 50 and over (and some younger adults with weakened immunity) can ask about the shingles vaccine.
Acyclovir or valacyclovir for daily suppressive therapy
For people with frequent genital herpes outbreaks, taking an antiviral every day can cut recurrences by around 70–80%. Both drugs work for suppression; valacyclovir is the only one approved to also reduce the risk of passing genital herpes to a partner.
| Acyclovir | Valacyclovir | |
|---|---|---|
| Daily dose | 400 mg twice a day | 500 mg or 1 g once a day |
| Notes | Cheaper for long-term use | 500 mg may be less effective with 10 or more outbreaks a year; 1 g is then preferred |
| Partner transmission | Not specifically approved | Approved; 500 mg daily cut transmission by about half in a key trial (Corey et al., 2004) |
Source: CDC 2021 STI Treatment Guidelines; valacyclovir FDA label.
Outbreaks often become less frequent over time, so doctors usually review suppressive therapy about once a year to decide whether it is still needed.
Chickenpox
Both drugs are approved for chickenpox in children aged 2 and over, dosed by body weight. Treatment should start within 24 hours of the rash appearing. Acyclovir’s liquid form makes it the more practical choice for young children.
Side effects and safety compared
The side effects of acyclovir and valacyclovir are nearly identical, because both end up as acyclovir in your body. Most people take either drug without problems.
Common side effects
- Headache (the most frequently reported)
- Nausea and stomach pain
- Diarrhoea or vomiting, more often with oral acyclovir
- Dizziness or tiredness
Cream and ointment forms of acyclovir can cause mild burning, stinging or dryness where applied.
Serious side effects
These are rare. Contact a doctor promptly if you notice:
- Signs of kidney problems: passing much less urine, swelling in the legs, unusual tiredness
- Confusion, agitation, hallucinations, tremor or trouble speaking (more likely in older adults and people with kidney disease)
- Signs of an allergic reaction: rash, swelling of the face or throat, difficulty breathing
- Unusual bruising or bleeding, fever and pale skin: high doses of valacyclovir (8 g a day) have been linked to a rare blood-clotting disorder (TTP/HUS) in people with advanced HIV or transplants
Kidney function and hydration
Both drugs are cleared by the kidneys, so people with reduced kidney function need a lower dose or longer gap between doses. Drinking plenty of fluids while on treatment helps protect the kidneys. Tell your prescriber about any kidney condition before starting either drug.
Pregnancy and breastfeeding
Acyclovir and valacyclovir have both been used extensively in pregnancy without a clear increase in birth defects. For people with a history of genital herpes, guidelines commonly recommend starting suppressive therapy at 36 weeks of pregnancy to lower the chance of an outbreak at delivery. Both pass into breast milk in small amounts. Decisions in pregnancy or while breastfeeding should always be made with your doctor.
Can you take acyclovir and valacyclovir together?
No. Valacyclovir turns into acyclovir, so taking both at once doubles your acyclovir exposure and raises the risk of kidney and nervous-system side effects without adding any benefit. Take only the one you have been prescribed.
Both drugs can interact with other medicines that affect the kidneys, such as some anti-inflammatory painkillers and certain transplant drugs. Give your pharmacist a full list of what you take.
Cost, availability and switching
Which is cheaper?
Generic acyclovir is usually the cheaper of the two per course of treatment, and the gap matters most for daily suppressive therapy taken over months or years. Generic valacyclovir has become much more affordable since it lost patent protection, but it generally still costs more per day. Prices vary by pharmacy, country and insurance cover, so compare the cost of a full course rather than the price per tablet.
Switching from acyclovir to valacyclovir (or back)
Switching changes your dosing schedule, not the medicine working in your body. People often move to valacyclovir to take fewer tablets, or back to acyclovir to save money. Only switch on your prescriber’s advice, because the doses are not interchangeable milligram for milligram. Do not overlap the two drugs during a switch.
If you have a prescription for acyclovir, you can order genuine generic acyclovir 400 mg from acyclovir400mg.com. A valid prescription is required.
Acyclovir or valacyclovir: which should you ask your doctor about?
Both drugs work. The right one for you is usually the one that fits your situation and that you will take on schedule.
| Your situation | Often the better fit | Why |
|---|---|---|
| Cost is the main concern | Acyclovir | Generic is usually cheaper, especially long term |
| You want the fewest doses a day | Valacyclovir | Once or twice daily vs up to five times |
| Cold sore at the first tingle | Valacyclovir | One-day course |
| Daily suppression to protect a partner | Valacyclovir | Only one approved to reduce transmission |
| Child or trouble swallowing tablets | Acyclovir | Available as a liquid |
| Want to treat a lip sore directly | Acyclovir | Cream, ointment or buccal tablet |
| Shingles in an older adult | Valacyclovir | Three doses a day; may shorten nerve pain |
| Kidney disease | Either, adjusted | Both need a lower dose; doctor decides |
Whichever you are prescribed, start it as early as possible in an outbreak and finish the full course.
Frequently asked questions
The main difference is absorption. Valacyclovir is converted into acyclovir in the body, but about 55% of each dose is absorbed compared with 10–20% for acyclovir. That lets valacyclovir be taken once or twice a day, while acyclovir usually needs two to five doses a day.
Valacyclovir is not more effective, but it is more convenient. Clinical trials show similar healing times for both drugs at their recommended doses. Valacyclovir needs fewer doses a day, which helps people finish treatment, while acyclovir is usually cheaper and comes in more forms, including liquid and cream.
Neither is stronger as an antiviral, because both work as acyclovir inside the body. Valacyclovir delivers more acyclovir into the blood per tablet, so fewer doses are needed. Milligram amounts are not directly comparable: each drug’s dose is set to reach effective levels for the condition treated.
No, but they are closely related. Valtrex is the brand name of valacyclovir, a prodrug that your body converts into acyclovir. The antiviral effect is the same, but Valtrex is absorbed better, so it is dosed less often. Zovirax is the brand name for acyclovir itself.
Both are effective for cold sores, but valacyclovir is more convenient: a single day of treatment (2 g twice, 12 hours apart) started at the first tingle. Acyclovir is taken for several days by mouth or applied as a cream five times a day for four days.
They work at about the same speed. In trials of first-episode genital herpes, valacyclovir twice daily and acyclovir five times daily healed sores in similar times. For repeat outbreaks, valacyclovir allows a shorter course of three days. Starting either drug within a day of symptoms gives the best results.
Valacyclovir is often preferred for shingles. It is taken three times a day for 7 days instead of five times a day for 7–10 days, and in one major trial it shortened shingles-related nerve pain compared with acyclovir. Either drug should be started within 72 hours of the rash.
Both work for daily suppression: acyclovir 400 mg twice a day, or valacyclovir 500 mg to 1 g once a day. Valacyclovir is easier to remember and is the only one approved to reduce genital herpes transmission to a partner. Acyclovir is usually cheaper over the long term.
Yes, with your prescriber’s approval. Switching changes your dosing schedule, not the active medicine, because valacyclovir becomes acyclovir in the body. The doses are not interchangeable milligram for milligram, so your doctor will set the new dose. Do not take both drugs during the changeover.
No. Valacyclovir is converted into acyclovir, so taking both doubles your acyclovir exposure. This adds no benefit and raises the risk of side effects such as kidney problems, confusion and dizziness. Take only the antiviral you have been prescribed, at the prescribed dose.
Acyclovir is poorly absorbed from the gut, so only 10–20% of each dose reaches the blood, and it leaves the body within a few hours. Frequent doses keep levels high enough to stop the virus. Valacyclovir is absorbed far better, so fewer doses achieve the same effect.
Usually, yes. Generic acyclovir typically costs less per course than generic valacyclovir, and the saving adds up with long-term daily suppression. Actual prices depend on your pharmacy, country and insurance, so compare the cost of a full course rather than per tablet.
Do not rely on expired acyclovir to treat an outbreak, because it may have lost potency. Take it to a pharmacy or drug take-back program. If none is available, mix the tablets with used coffee grounds or cat litter, seal them in a bag and put them in household trash. Then ask for a fresh prescription.
Medical disclaimer
This article is for general information and does not replace advice from a doctor or pharmacist. Doses shown are standard adult doses for people with normal kidney function; your prescriber may recommend a different dose. Do not start, stop or change an antiviral without medical advice.
References
- Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021: Genital herpes.
- Valacyclovir hydrochloride tablets: FDA prescribing information.
- American Society of Health-System Pharmacists. Valacyclovir monograph.
- Fife KH, et al. Valaciclovir versus acyclovir in the treatment of first-episode genital herpes infection. Sexually Transmitted Diseases, 1997.
- Beutner KR, et al. Valaciclovir compared with acyclovir for improved therapy for herpes zoster in immunocompetent adults. Antimicrobial Agents and Chemotherapy, 1995.
- Corey L, et al. Once-daily valacyclovir to reduce the risk of transmission of genital herpes. New England Journal of Medicine, 2004.
