Acyclovir vs. Valacyclovir – Overview and Comparison

Cold sores are small blisters that appear around the mouth or on the lips and result from the herpes simplex virus type one (HSV-1). Herpes is a highly contagious virus that spreads through close contact, such as sexual contact or kissing, and cold sores can serve as a location that spreads the herpes virus. 

While antiviral medication cannot cure cold sores, it can help lessen their outbreaks and make them go away quicker. Two such antiviral medications are acyclovir and valacyclovir. 

Curious about the differences and similarities between acyclovir and valacyclovir? Continue reading to get a complete overview and comparison of these two medications.

Table of Contents

How Do Antivirals Treat Cold Sores?

Antiviral medications, such as Valtrex, limit the spread and growth of the HSV-1 virus, which makes cold sores less intense and also reduces other symptoms associated with HSV-1 infection. 

Antiviral drugs do not kill viruses, but they do keep viruses from growing and multiplying. This not only lessens the intensity of a viral outbreak, such as cold sores but also allows the immune system to fight the infection, which can help shorten the length of a cold sore. 

What Is Acyclovir?

Acyclovir belongs to the class of antiviral medications called synthetic nucleoside analogs and works to stop the spread of the herpes virus throughout the body. It can help treat the symptoms of herpes of the genitals, skin, mucous membranes (mouth and lips), and brain. Other viral infections that acyclovir can help manage include chickenpox and shingles. 

Acyclovir can come as a tablet, capsule, liquid suspension, cream, or injection. 

The brand name of acyclovir is Zovirax, and it attacks the virus’s DNA and prevents it from multiplying.

What Is Valacyclovir?

Valacyclovir is another antiviral drug that helps treat shingles, genital herpes, and cold sores. Like acyclovir, it does not cure herpes infections. Instead, it allows the sores to heal, decreases pain and itching, and prevents new sores from forming. 

The brand name of valacyclovir is Valtrex, and it is available as an oral tablet.

Valacyclovir is considered a prodrug of acyclovir, which means that it turns into acyclovir in the body. It then binds to the DNA of HSV1 and stops it from replicating. 

Acyclovir vs. Valacyclovir

Acyclovir and Valacyclovir are both antivirals treating similar infections, and they generally have many similarities. However, there are a few differences between these two drugs. Let’s break down each drug, part by part, to see how they compare.

UsesAcyclovir and Valacyclovir both treat chickenpox, shingles, and mouth, lip, and genital herpes.
Acyclovir also treats herpes of the brain and herpes in newborns.
DosageValacyclovir has a longer duration of action, so it is usually taken only twice a day for 5 days. As for Acyclovir, it is generally prescribed 3 times per day for 7 to 10 days.
EffectivenessAcyclovir and valacyclovir are equally effective and should be taken immediately after symptoms appear.
Side EffectsBoth acyclovir and valacyclovir have a list of possible common side effects. There are also severe side effects associated with each drug. 
WarningsBoth drugs can harm the kidneys and should not be taken alongside other medications that can affect the kidneys. 


Since valacyclovir is a prodrug of acyclovir, the drugs work similarly to bind to the virus’s DNA and stop it from replicating. They are also used to treat the same infections, such as chickenpox, shingles, and herpes that affect the genitals, mouth, or lips. However, acyclovir can also be used to treat herpes of the brain and herpes in newborns.

Dosage and Usage

It is recommended to take acyclovir and valacyclovir as soon as you first notice symptoms of a herpes outbreak, such as blisters, burning, or tingling. 

For those taking a buccal tablet, place the flat side of the tablet against your upper gum on the same side as your cold sore. Allow the tablet to dissolve throughout the day. Do not chew, crush, or suck on the tablet.

For those taking a liquid suspension, make sure to shake it before measuring out a dose. 

Dosing for acyclovir is based on weight, especially in children and teenagers. When prescribed for herpes, it is generally taken 3 times per day for 7-10 days.

Valacyclovir is prescribed as a tablet taken by mouth, usually every 8 hours for 7 days when treating shingles, and twice a day for 5 days to treat genital herpes. 

When taking acyclovir and valacyclovir, be sure to drink plenty of water to keep the kidneys working optimally.


To ensure the optimal effectiveness of both medications, continue taking them for the complete prescription, even if the symptoms quickly improve. When taking medicine, a herpes outbreak usually lasts 1-2 weeks. 

Both antiviral drugs target the same viruses, the primary difference between them is that valacyclovir has a longer duration of action, meaning it requires fewer doses each day to achieve the same effect as acyclovir. This longer duration of action can be considerable, with valacyclovir sometimes taken twice a day and acyclovir potentially taken up to five times a day. 

However, the effectiveness of the two drugs has been shown to be the same. One trial comparing the two drugs found that participants taking acyclovir and valacyclovir displayed similar results after taking them for a year. 

Side Effects

The common side effects of acyclovir can include:

  • rash
  • itching
  • mild skin pain
  • headache
  • nausea
  • vomiting
  • diarrhea
  • mouth pain (if taking a buccal tablet)

Valacyclovir has similar common side effects, such as:

  • upset stomach
  • headache
  • vomiting
  • constipation
  • diarrhea

Some people who take acyclovir or valacyclovir may experience an allergic reaction with symptoms such as difficulty breathing, hives, or swelling of the lips, tongue, face, or throat. Seek emergency medical attention if you experience any of these symptoms. 

Additional severe side effects of acyclovir and valacyclovir include:

  • changes in behavior
  • easy bleeding or bruising; red or purple pinpoint spots under the skin
  • hallucinations
  • confusion
  • seizures
  • signs of kidney problem (e.g., little or no urinating, swelling in the feet or ankles, difficult or painful urination, feeling short of breath or tired)

Acyclovir can also have the following side effects:

  • rapid heartbeat
  • weakness
  • difficulty sleeping
  • aggressive behavior
  • loss of consciousness

As for valacyclovir, anyone who experiences the following severe side effects should contact their doctor immediately:

  • itching
  • rash
  • yellowness of the eyes or skin
  • confusion
  • blood in the urine
  • fever

Drug Interactions

Taking acyclovir or valacyclovir with certain medications for infections, osteoporosis, cancer, bowel disorders, organ transplant rejection, pain, arthritis, or high blood pressure can harm the kidneys. 

There are also other drugs that may affect acyclovir, including Benadryl, probenecid (Benemid),  Lexapro, amphotericin B (Fungizone), Nexium, HIV medications, sulphonamides, NSAIDs, etc. For the complete list, check with your doctor. 

Valacyclovir also has a list of drugs it can interact with, including medications for thyroid disorders, Cymbalta, Benadryl, and various vitamins (e.g., B12, C, D3). If you take any medications or supplements, inform your doctor before starting valacyclovir. 


For either medication, inform your doctor if you’re allergic to acyclovir or valacyclovir.

Those who take valacyclovir should first let their doctor know if they have HIV/AIDS, kidney disease (or are on dialysis), a weak immune system, or if they have had a bone marrow or kidney transplant. Those taking acyclovir should also let their doctor know of any kidney problems—acyclovir and valacyclovir can harm the kidneys, and this damage can increase if taken alongside other medications that can harm the kidneys. 

Furthermore, neither acyclovir or valacyclovir can stop the spread of herpes. These infections are contagious, and you can still spread the infection even if you are taking one of these medicines. One small study did find that those who took valacyclovir were less likely to spread the herpes virus, but these findings require additional and larger-scale studies to fully confirm. As such, be sure to avoid sexual intercourse or use a condom to prevent the spread of this virus to others. 


The cost of acyclovir oral capsules is around $11 for a supply of five 200 mg capsules. These prices are for those without insurance. However, this medication is covered by most insurance and Medicare plans, so you may get it for a cheaper price. 

As for valacyclovir, the price without insurance is around $19 for ten 500 mg tablets.


Is valacyclovir the same as acyclovir?

Valacyclovir is considered a prodrug of acyclovir, which means that it turns into acyclovir in the body. So, it is not the same as acyclovir, but it is very similar, treating the same infections and working in a similar manner. 

Is valacyclovir more potent than acyclovir?

Valacyclovir has been shown to have a greater bioavailability than acyclovir and a longer duration of action, which means it can be more potent than acyclovir and may clear up an infection faster. However, both drugs display similar effectiveness. 

Which is more effective, acyclovir or valacyclovir?

Acyclovir and valacyclovir work similarly and have displayed the same level of effectiveness in research studies. The most significant difference between the two drugs is that valacyclovir has a longer duration of action, so it requires fewer doses during the day. However, in regard to limiting the spread of herpes, valacyclovir, in a small study, did show greater promise, although these results need further studies to confirm them. 

Is acyclovir or valacyclovir better for shingles?

While both acyclovir and valacyclovir work similarly, valacyclovir has been shown to work a little bit faster in clearing up shingles infections. 

What is the difference between aciclovir and acyclovir?

These are two names for the same drug. Aciclovir is the international nonproprietary name (INN) and British Approved Name (BAN), whereas acyclovir is the name used in the United States. Acyclovir used to be the BAN. 

How Can DrHouse Help You?

If you notice the symptoms of an oncoming herpes outbreak, such as tingling, burning, or cold sores, reach out to your doctor about starting an antiviral drug such as acyclovir or valacyclovir. These drugs work best when started as soon as you notice symptoms, and DrHouse can help you get medication fast. 

With DrHouse, you can meet with an online doctor in just 15 minutes, helping you get your antiviral prescription quickly and conveniently. 

Key Takeaways

Acyclovir and valacyclovir are two antiviral drugs used to treat chickenpox, shingles, and herpes. Specifically, they can help a herpes outbreak, such as cold sores, go away quicker than without treatment. These drugs do not kill the virus but keep it from replicating, which helps lessen the severity of a herpes outbreak.

Valacyclovir is a prodrug of acyclovir, which means it becomes acyclovir in the body. As such, these two drugs are similar and exhibit the same levels of effectiveness. The greatest difference between them is that valacyclovir has a longer duration of action, so it does not need to be taken as frequently or for as long.

If you notice the symptoms of a herpes outbreak starting, reach out to your doctor and enquire about starting an antiviral medication to help tone down the severity of your outbreak. 


Content on the DrHouse website is written by our medical content team and reviewed by qualified MDs, PhDs, NPs, and PharmDs. We follow strict content creation guidelines to ensure accurate medical information. However, this content is for informational purposes only and not a substitute for professional medical advice, diagnosis, or treatment. For more information read our medical disclaimer.

Always consult with your physician or other qualified health providers about medical concerns. Never disregard professional medical advice or delay seeking it based on what you read on this website.

If you are experiencing high fever (>103F/39.4C), shortness of breath, difficulty breathing, chest pain, heart palpitations, abnormal bruising, abnormal bleeding, extreme fatigue, dizziness, new weakness or paralysis, difficulty with speech, confusion, extreme pain in any body part, or inability to remain hydrated or keep down fluids or feel you may have any other life-threatening condition, please go to the emergency department or call 911 immediately.



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