The Key Differences Between Acyclovir and Valacyclovir

Published: 2025-08-19

Updated: 2025-08-19

3 mins

Antiviral medications play an important role in managing infections caused by herpes viruses. These drugs don’t cure the viruses, but they help shorten outbreaks, ease symptoms, reduce transmission risk, and in some cases, prevent recurrences altogether.

Two of the most commonly prescribed options are acyclovir and valacyclovir. Both target the same viruses – including herpes simplex (HSV-1 and HSV-2) and varicella-zoster virus (which causes chickenpox and shingles) – but they differ in how they’re absorbed, how often they’re taken, and sometimes in cost.

In this article, we’ll compare acyclovir and valacyclovir side by side, covering their approved uses, dosing schedules, benefits, side effects, costs, and the key similarities and differences that may influence which medication is right for you.

What are Acyclovir and Valacyclovir?

Acyclovir was the first widely used antiviral medication for herpes virus infections, earning FDA approval in the 1980s. It’s been trusted for decades to help manage outbreaks and provide relief from symptoms. 

Valacyclovir came later and is what’s known as a prodrug of acyclovir. That means once it’s taken, the body converts it into acyclovir. This design allows the medication to be absorbed more efficiently, so patients can take it less often while still getting the same benefits.

Both drugs work in the same way: they block the virus’s ability to replicate its DNA. By interfering with this process, they can reduce the severity and duration of outbreaks and, in some cases, help prevent them from happening as often.

The viruses they’re most commonly prescribed for include:

• HSV-1 (oral herpes, often called cold sores)

• HSV-2 (genital herpes)

• Varicella-zoster virus (the cause of chickenpox and shingles)

Approved Uses and Off-Label Uses

Both acyclovir and valacyclovir are FDA-approved for treating infections caused by herpes viruses, though their specific approvals differ slightly.

FDA-approved uses

Genital herpes: Both medications are used to treat active outbreaks and can also be prescribed for long-term suppression to reduce the frequency of recurrences.

Cold sores (orolabial herpes): Valacyclovir is specifically approved for treating cold sores, while acyclovir is commonly used off-label for the same purpose.

Shingles (herpes zoster): Both drugs can shorten the duration and intensity of shingles outbreaks.

Chickenpox (varicella): Acyclovir is approved for treating chickenpox in children and adults. Valacyclovir isn’t formally approved for chickenpox but may be prescribed in certain cases.

Common off-label uses

Prevention in immunocompromised patients: Both drugs may be prescribed to prevent herpes infections in people with weakened immune systems, such as those undergoing chemotherapy or organ transplantation.

Ocular herpes (herpes simplex keratitis): Acyclovir is often used to manage herpes-related eye infections, helping prevent vision-threatening complications.

Other herpes virus infections: Doctors may also use these antivirals in specialized cases, such as Epstein-Barr virus (EBV)-related conditions, though this is less common.

Dosage and Administration

One of the biggest differences between acyclovir and valacyclovir is how often they need to be taken.

Acyclovir has a shorter half-life in the body, which means it doesn’t stay active for very long. Because of this, it typically requires multiple doses throughout the day – sometimes up to five times daily during an outbreak. This frequent dosing can be effective but may be harder for some patients to stick to consistently.

Valacyclovir has much better absorption (higher bioavailability). Once converted into acyclovir in the body, it remains effective longer, so it’s usually taken only once or twice daily, depending on whether it’s being used for treatment or suppression. This less demanding schedule often makes it easier for patients to follow.

In terms of forms, both are available as oral tablets, while acyclovir also comes in a liquid suspension (often prescribed for children) and an IV formulation used in hospitals for severe or complicated infections.

From a convenience standpoint, valacyclovir often has the advantage, but acyclovir’s different formulations can be important for patients who need alternatives beyond oral tablets.

Effectiveness and Benefits

When it comes to controlling herpes virus infections, acyclovir and valacyclovir are equally effective if taken as prescribed. Both reduce the severity and length of outbreaks, help lesions heal more quickly, and can be used for long-term suppression to lower the risk of recurrences.

The main distinction lies in how the body processes them. For many patients, this simpler schedule, that valacyclovir allows for, makes treatment easier to follow. This can improve consistency and overall results.

Acyclovir, while less convenient in terms of dosing, has the advantage of a long track record – it’s been trusted for decades. It’s also available as an IV form for severe infections and a liquid suspension for children or anyone who has trouble swallowing pills.

In practice, both drugs are highly reliable, and the “better” choice often comes down to convenience, cost, and individual patient needs.

Side Effects and Safety

Acyclovir and valacyclovir share very similar safety profiles, since valacyclovir is converted into acyclovir once inside the body.

Common side effects include mild issues like nausea, headache, or abdominal discomfort. These are usually temporary and manageable for most patients.

Rare but more serious side effects can occur, especially with higher doses or in people with underlying health conditions. These may include kidney problems or central nervous system effects such as confusion, agitation, or dizziness.

Both medications are generally safe, but special care is needed for older adults and people with kidney impairment, since the drugs are cleared through the kidneys. In these cases, doctors may adjust the dose to reduce the risk of complications.

Overall, both antivirals are well-tolerated, and most patients use them without significant problems when taken as directed.

Cost Comparison

Acyclovir is typically the more affordable option. It’s been available as a generic for decades, which makes it widely accessible at a lower price point.

Valacyclovir is also available in generic form, but it often costs more than acyclovir. The difference isn’t always significant, but for patients who need long-term suppression therapy, even small price differences can add up over time.

Insurance coverage can help offset costs for both medications, but the out-of-pocket price will vary depending on the pharmacy, insurance plan, and whether the prescription is filled with a brand-name or generic version. Some patients may find that their plan favors one drug over the other.

How Rex MD Can Help

Whether it’s cold sores around your mouth or itchiness down there, Rex MD can help relieve your symptoms and suppress outbreaks. If clinically appropriate, a licensed physician can prescribe valacyclovir for your infection.

Get started today to consult with a healthcare provider about your condition from the comfort of home.