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Acyclovir vs Valacyclovir: Which Is Better?

Katelyn Hagerty

Reviewed by Katelyn Hagerty, FNP

Written by Geoffrey C. Whittaker

Published 12/18/2018

Updated 10/19/2023

Cold sores and their even-less-pleasant cousins are a pain — even the relatively small portion of the population without them knows this.

If you’ve got a viral herpes outbreak, you’re typically going to want to talk to a healthcare provider about medications ASAP. But before you seek medical advice, we understand the desire to read up. 

Below we’ve covered the differences and similarities between two of the most commonly prescribed medications for herpes viral outbreaks: acyclovir and valacyclovir.

Before going for that prescription medication, read on to learn about the common side effects, drug interactions, the difference between acyclovir and valacyclovir and other things to know.

Prescription drugs for the treatment of herpes like valacyclovir and acyclovir are antiviral drugs, which inhibit the virus from multiplying (or reproducing).

Drugs for herpes simplex virus 1 or herpes simplex virus 2 (HSV-1 or HSV-2) infections don’t cure herpes, but they can get outbreaks under control and treat their symptoms. These antiviral herpes drugs can also be used as part of a suppressive therapy plan to reduce outbreak severity and frequency.

Now let’s look at each one in more detail.

What Is Valacyclovir?

Valacyclovir is one of the most (if not the most) widely used drugs worldwide for treating herpes, and has been since 1995, when it gained approval by the Food and Drug Administration (FDA). Most people know this drug as the brand name medication Valtrex, though generics are easier to come by these days.

Valacyclovir is what’s referred to as a prodrug of acyclovir, meaning it converts to acyclovir inside of your body. So, after you take a valacyclovir tablet, your body turns it into acyclovir, which then blocks the herpes virus from reproducing.

What Is Acyclovir?

Acyclovir, or ACV, is an older antiviral medication commonly used to treat herpes. It’s effective against HSV-1, HSV-2 and shingles.

Acyclovir — which was initially sold under the name Zovirax — was discovered in the 1970s, and it was the most widely used option until alternative antiviral drugs like valacyclovir became the standard for modern herpes management.

The effects of acyclovir are basically the same as valacyclovir (remember that one converts to the other).

In the war between you and herpes, there’s no perfect weapon, so in the valacyclovir vs. acyclovir debate, there’s no clear winner. Both are safe and have been proven effective as treatments for: 

  • HSV-1

  • HSV-2

  • Herpes zoster shingles 

  • Other forms of the herpes virus

That said, there are some reasons you and your healthcare provider might choose one over the other — and that choice is often valacyclovir. 

Like other herpes medications, valacyclovir has shown great results — studies show it reduces the amount of time required for healing during an outbreak and that it reduces your risk of transmitting the herpes virus to other people.

Setting aside clinical trial results and double-blind data from these studies, however, there are some practical reasons that you might prefer one medication to another.

What sets valacyclovir apart is that it works almost immediately, and its effects may also last longer than the effects of other medications. 

In fact, one of top main reasons you may choose valacyclovir over acyclovir for herpes and cold sores is because of its improved bioavailability (another word for how much of the drug is absorbed), which allows a lower dose of the drug to be used in treatment.

For example, one study showed that a smaller 500mg dose of valacyclovir is as effective as a larger 800mg dose of acyclovir in preventing recurrence of herpes simplex virus-related eye disease.

Acyclovir will be almost completely broken down by the liver when taken as an oral tablet, leaving it a bioavailability of just about 12 percent. Meanwhile, a valacyclovir tablet can have an oral bioavailability of approximately 50 percent. We may not be great at math, but we know that’s several times better.

And what it means is that more of the oral valacyclovir makes it into your body in the first place, which means that you can potentially take it fewer times per day or week to get the same results.

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Side effects for both medications are generally mild and limited when the medication is used correctly.

The side effects of valacyclovir include:

  • Headache

  • Abdominal pain

  • Nausea

Side effects of acyclovir reported by users include:

  • Diarrhea 

  • Headache

  • Nausea 

That said, both medications should be used only as directed. You should also let a healthcare professional know if you have other viral infections, kidney disease or HIV, or are immunocompromised. 

People who are breastfeeding should not take either medication without talking to a healthcare professional first, so if you take these medications, keep your pills away from anyone pregnant or postpartum.

Whether you’re dealing with the lesions from a particularly aggressive strain of shingles or the unfortunate symptoms of a herpes simplex virus breakout, you’re going to want some medication to help you deal with those uncomfortable (and embarrassing) blisters, ASAP. Medications like acyclovir and valacyclovir are among your many options to deal with them.

If you think you might have herpes, the best approach is to speak to your healthcare provider about treatment options. Your doctor will be able to provide advice on the most effective drug for treating herpes based on your symptoms, immune system, lifestyle and overall health.

That said, here are some guidelines to keep in mind before you talk to them:

  • Both antivirals for herpes are effective, and they even share some DNA, as your body breaks valacyclovir down into acyclovir.

  • Oral valacyclovir will likely be the first medication prescribed to you for a herpes outbreak or the management of recurrent genital herpes. It’s cheap, effective and readily available, as well as newer and more bioavailable than acyclovir.

  • None of the antiviral drugs on the market today can cure herpes. However, consistent use of an antiviral drug can make living with herpes much easier by speeding up healing after an outbreak and reducing your risk of transmitting the virus to other people.

Our valacyclovir 101 guide includes more information on this drug, including common dosages, potential side effects, interactions and brand names.

We’ve also got valuable information for you on valacyclovir dosages, how long valacyclovir takes to work and sexual health questions like the safety concerns of having sex with herpes

Ready to get the help and education you need? We’re just a click away.

6 Sources

  1. Spruance, S. L., Jones, T. M., Blatter, M. M., Vargas-Cortes, M., Barber, J., Hill, J., Goldstein, D., & Schultz, M. (2003). High-dose, short-duration, early valacyclovir therapy for episodic treatment of cold sores: results of two randomized, placebo-controlled, multicenter studies. Antimicrobial agents and chemotherapy, 47(3), 1072–1080. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC149313/.
  2. Valtrex (valacyclovir hydrochloride) Caplets - Food and Drug Administration. (n.d.-b). https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/020487s014lbl.pdf.
  3. Prescribing information zovirax - food and drug administration. (n.d.-a). https://www.accessdata.fda.gov/drugsatfda_docs/label/2005/018828s030,020089s019,019909s020lbl.pdf.
  4. Miserocchi, E., Modorati, G., Galli, L., & Rama, P. (2007). Efficacy of valacyclovir vs acyclovir for the prevention of recurrent herpes simplex virus eye disease: a pilot study. American journal of ophthalmology, 144(4), 547–551. https://pubmed.ncbi.nlm.nih.gov/17692271/.
  5. Bonnar P. E. (2009). Suppressive valacyclovir therapy to reduce genital herpes transmission: good public health policy?. McGill journal of medicine : MJM : an international forum for the advancement of medical sciences by students, 12(1), 39–46. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2687913/.
  6. Nair PA, Patel BC. Herpes Zoster. [Updated 2023 Apr 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441824/.
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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.