Valtrex vs Acyclovir: Which Is Better for Cold Sores?

By Arielle Mitton
Medically reviewed checkmarkMedically reviewed
July 25, 2022

Cold sores, also called fever blisters, are small painful blisters that appear on the lips or around the mouth. They are caused by type one herpes simplex virus (HSV-1).

Herpes is highly contagious and spreads through close contact such as kissing or sexual contact.

It can also spread by sharing an infected person’s utensils, razors, or towels.  

Cold sores can’t be cured, but you can manage outbreaks with herpes medications like valacyclovir (Valtrex) and acyclovir (Zovirax).

In this article, I’ll discuss how antivirals help cold sores and how valacylovir compares with acyclovir.

I’ll explain the effectiveness of valacyclovir and acyclovir as well as the side effects and costs of both medications.

Finally, I’ll discuss which is better for cold sores. 

How Do Antivirals Treat Cold Sores?

Antiviral medications don’t kill viruses directly.

Instead, they stop them by inhibiting their ability to develop and multiply.

In essence, antivirals treat cold sores by limiting how much the herpes virus can grow and spread, which reduces the intensity of symptoms. 

Different antivirals have unique mechanisms of action.

Here’s how valacyclovir and acyclovir treat cold sores.

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Valacyclovir (brand name Valtrex) is a prodrug of acyclovir, meaning it turns into acyclovir in the body.

Valacyclovir treats cold sores by binding to the DNA of the herpes simplex virus and stopping it from replicating. 

You can only get oral tablets of Valtrex by prescription


Acyclovir (Zovirax) treats cold sores by attacking the virus’s DNA and stopping it from multiplying.

While it doesn’t remove the herpes virus from your body, it helps manage symptoms and improves healing time of a cold sore.

Acyclovir is a prescription-only medication available as injections, tablets, oral suspensions, or creams.

Valacyclovir vs. Acyclovir

Because valacyclovir is a prodrug of acyclovir, the two drugs work similarly.

They both bind to the DNA of viruses and stop viral replication. 

Valacyclovir and acyclovir are used to treat:

Acyclovir is also used to treat herpes simplex encephalitis (herpes of the brain) and herpes in newborn babies. 


Valacyclovir and acyclovir work similarly.

In one study, participants who took valacyclovir and acyclovir showed similar results after taking the medications for a year. 

The main difference between the drugs is that valacyclovir has more bioavailability and a longer duration of action than acyclovir.

This means valacyclovir can be taken fewer times in a day than acyclovir and still have the same effect.

For example, valacyclovir is taken two times daily, while acyclovir might be taken up to five times daily depending on what it is treating. 

One small study also showed that people who took valacyclovir were less likely to spread the herpes virus than those who took acyclovir. 

Side Effects 

Here are some side effects of these medications. 


Common side effects of Valtrex include:

Other less common side effects of this medicine include: 

Talk to your healthcare provider immediately if you notice any side effects. 


Common side effects of acyclovir include:

Acyclovir may also cause more serious side effects.

Speak to your healthcare provider if you notice any of these side effects: 

  • Itching
  • Hives
  • Rashes 
  • Swelling of the tongue, lips, face, throat, and limbs
  • Trouble breathing 
  • Rapid heartbeat
  • Weakness
  • Trouble sleeping
  • Fever
  • Blood in urine
  • Bloody diarrhea 
  • Confusion
  • Aggressive behavior
  • Seizures
  • Hallucinations
  • Loss of consciousness 

Interactions and Warnings

Drug interactions can affect how your medications work or increase your risk of side effects.

Here are some things to keep in mind when taking valacyclovir or acyclovir. 


Before taking Valtrex, tell your healthcare provider:

  • If you’re allergic to valacyclovir or acyclovir. 
  • What medications you’re taking, especially if you’re taking probenecid (Benemid), cimetidine (Tagamet), or vitamins.
  • If you have liver or kidney problems, HIV or AIDS, or any immune system problems. 


Before taking acyclovir, tell your healthcare provider:

  • If you’re allergic to valacyclovir, acyclovir, and any other medications. 
  • If you’re pregnant, breastfeeding, or plan to become pregnant.
  • Your current health state, especially if you have liver or kidney diseases, HIV or AIDS, or any immune system problems.
  • All medications you’re currently taking, including vitamins, nutritional supplements, and herbal products. 

The following medications may interact with acyclovir, so inform your healthcare provider if you’re taking them: 

  • Amphotericin B (Fungizone)
  • Probenecid (Benemid)
  • Sulphonamides (Bactrim)
  • Non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen 
  • HIV medications (Retrovir)


The cost of your medication depends on whether you’re buying a generic or branded drug, your insurance coverage, and your pharmacy. 


Without insurance, 30 tablets of 500-mg Valtrex 500 costs around $421. With or without insurance, generic valacyclovir costs less than branded Valtrex. 


Generic acyclovir costs around $19 without insurance.

However, it’s covered by most Medicare and insurance plans, so you may get it for cheaper. 

Which Is Better for Cold Sores?

Valacyclovir is the most effective treatment for cold sores.

It prevents the herpes simplex virus from spreading in the body and speeds the healing of cold sores.

Although acyclovir is also effective, valacyclovir has a longer duration of action and plasma availability, so it can be taken fewer times in a day.

However, acyclovir’s price makes it the preferred option for many people considering that the efficacy is equal when taken at proper dosing intervals.

Concerned about cold sores? Chat with a provider through K Health.

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When to See a Medical Professional 

Seek medical advice if you notice any serious adverse effects while taking valacyclovir or acyclovir.

Also see a medical professional if:

  • The cold sores don’t heal within 10 days of taking your medication
  • You have frequent outbreaks
  • You have swollen gums and sores in your mouth
  • Your immune system is weakened
  • You have new or worsening symptoms despite the treatment

How K Health Can Help

Did you know you can get affordable Primary Care with the K Health app?

Download K Health to check your symptoms, explore conditions and treatments, and if needed text with a healthcare provider in minutes. 

K Health’s AI-powered app is based on 20 years of clinical data.

Frequently Asked Questions

Are acyclovir and valacyclovir the same?
Acyclovir and valacyclovir are different antiviral drugs. However, valacyclovir is a prodrug of acyclovir, meaning it turns into acyclovir after it's taken into the body.
Can I take Valtrex and acyclovir together?
No, you cannot take Valtrex and acyclovir together. They are similar drugs and combining them means taking an unsafe dose.
Is acyclovir or Valtrex better for shingles?
Acyclovir and valacyclovir have similar actions, but valacyclovir works slightly faster than acyclovir does on shingles.
Is valacyclovir superior to acyclovir?
Valacyclovir's advantage over acyclovir is that it has a longer duration of action in the body and can be taken fewer times a day. However, acyclovir’s price point often makes it the treatment of choice.

K Health articles are all written and reviewed by MDs, PhDs, NPs, or PharmDs and are for informational purposes only. This information does not constitute and should not be relied on for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment.

Arielle Mitton

Dr. Mitton is a board certified internal medicine physician with over 6 years of experience in urgent care and additional training in geriatric medicine. She completed her trainings at Mount Sinai Hospital and UCLA. She is on the board of the Hyperemesis Research Foundation to help women suffering from hyperemesis gravidarum.