Acyclovir vs. valacyclovir: Differences and similarities explained

In this article:

• Main differences
• Conditions treated
• Is acyclovir or valacyclovir better?
• Insurance coverage and cost of acyclovir vs. valacyclovir
• Common side effects of acyclovir vs. valacyclovir
• Drug interactions of acyclovir vs. valacyclovir
• Acyclovir and valacyclovir warnings
• FAQs

In this article

• Main differences
• Conditions treated
• Is acyclovir or valacyclovir better?
• Insurance coverage and cost of acyclovir vs. valacyclovir
• Common side effects of acyclovir vs. valacyclovir
• Drug interactions of acyclovir vs. valacyclovir
• Acyclovir and valacyclovir warnings
• FAQs

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) are viral infections that can last a lifetime. HSV-1 most often shows up as cold sores or eye infections, while HSV-2 is typically associated with genital lesions. VZV is the virus behind chickenpox and, later in life, shingles when it reactivates. Acyclovir and valacyclovir are two commonly prescribed antiviral drugs for these infections. They work by stopping the virus from multiplying, which helps shorten outbreaks and prevent flare-ups. Although they work in similar ways, they’re not identical. 

What are the main differences between acyclovir and valacyclovir?

Acyclovir and valacyclovir are both generic antiviral drugs that work by blocking viral replication. However, their main differences lie in how they’re absorbed and how often they must be taken. 

Acyclovir, known by the brand names Zovirax and Sitavig, has generally poor oral bioavailability or absorption into the body. That means it often needs to be taken several times per day. However, it’s available in more dosage forms than valacyclovir, such as an oral tablet, cream, ointment, and oral suspension. 

Valacyclovir, known by the brand name Valtrex, is a prodrug of acyclovir. In other words, it’s converted into acyclovir as its active form in the body. Valacyclovir comes as an oral tablet that is absorbed better than acyclovir and may have more convenient dosing schedules, with tablets that can be taken once or twice daily. For many people, valacyclovir works better and faster to manage HSV and VZV infections. 

Conditions treated by acyclovir and valacyclovir

Acyclovir and valacyclovir are both approved to treat infections caused by the herpes simplex virus and varicella-zoster virus. They can manage common conditions like cold sores (oral herpes), genital herpes, chickenpox, and shingles. Both medications can also be used long-term to help prevent recurrent outbreaks.

Acyclovir and valacyclovir may also be used for off-label purposes, or uses beyond what they’re approved for, based on clinical studies. For example, acyclovir is sometimes used for complications of shingles, like nerve inflammation (myelopathy) or more serious infections that spread inside the body. Valacyclovir may be used off-label to treat acute retinal necrosis, a serious eye infection that can affect vision.

Is acyclovir or valacyclovir more effective?

Both acyclovir and valacyclovir are effective antiviral treatments. According to one large randomized trial of first-episode genital herpes, valacyclovir (1,000 mg twice daily) and acyclovir (200 mg five times daily) showed no significant difference in time to healing, pain duration, or viral shedding. However, valacyclovir was noted to have a more convenient dosing schedule.

A larger network meta-analysis that reviewed 17 trials on shingles-related pain found that antiviral medications vary in how well they help with pain over time. While famciclovir ranked highest for preventing long-term nerve pain, valacyclovir ranked first in reducing pain 28 to 30 days after the shingles rash began. While all oral antivirals were well-tolerated, valacyclovir was found to be one of the more effective short-term options.

Valacyclovir may have an advantage over acyclovir in terms of convenience and potential effectiveness for shingles-related pain, but the best medication isn’t always black and white. A healthcare provider can help determine the best option based on a person’s overall condition. 

Insurance coverage and cost of acyclovir vs. valacyclovir

Acyclovir is a prescription medication covered by most commercial and Medicare insurance plans. The out-of-pocket price for acyclovir costs an average of $102 without insurance, but with an acyclovir coupon from SingleCare, you could pay less than $10 at participating pharmacies.

Valacyclovir is also covered by most commercial and Medicare plans. However, it costs more than acyclovir, at an average retail price of $211 without insurance. However, a coupon from SingleCare could lower the price of valacyclovir to about $11.

Prescription drug prices often change. These are the most accurate medication prices at the time of publishing in ZIP code 23666 as of Dec. 18, 2025. Click the link under “Get coupon” to see the latest drug prices.

Common side effects of acyclovir vs. valacyclovir

Acyclovir and valacyclovir have similar side effects since valacyclovir is converted into acyclovir in the body. Most side effects are mild and temporary. They usually go away as the body gets used to the medication.

Common side effects of acyclovir and valacyclovir include:

• Nausea
• Vomiting
• Stomach pain
• Diarrhea
• Headache
• Dizziness

Serious side effects are rare but possible, including severe kidney problems, severe skin rash, and psychiatric reactions like confusion, agitation, and hallucinations. Allergic reactions may also occur. It’s important to seek immediate medical attention if any serious adverse effects arise. 

Drug interactions of acyclovir vs. valacyclovir

Both antivirals can affect the kidneys and may interact with other medications that also have potential negative effects on the kidneys. Some drug interactions with acyclovir and valacyclovir may cause kidney damage.

Certain medications, such as cidofovir, foscarnet, and some injectable antibiotics, should generally not be used together with acyclovir or valacyclovir due to an increased risk of kidney toxicity. Nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen and naproxen can also worsen the stress on the kidneys when taken with these antivirals, especially in dehydrated or older adults.

In addition, both drugs may reduce the effectiveness of live varicella (chickenpox) and zoster (shingles) vaccines. Healthcare providers may recommend temporarily stopping acyclovir or valacyclovir before getting vaccinated.

Warnings of acyclovir and valacyclovir

Acyclovir and valacyclovir should not be used in anyone who has had an allergic reaction to either medication. Because these drugs are closely related, people with allergies to similar antivirals, such as famciclovir, penciclovir, or valganciclovir, may also be at higher risk of an allergic reaction.

Both medications are processed through the kidneys, and people with kidney problems may need dosage changes to avoid potential side effects. Taking too much or taking them too often while having reduced kidney function may increase the risk of neurotoxic side effects such as confusion, agitation, or hallucinations. These symptoms are more common in older adults or those who are dehydrated.

In rare cases, high doses of valacyclovir and acyclovir have been linked to a serious condition called thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). However, it has mainly been reported in people with advanced HIV or those who have had certain types of transplants. Treatment should be stopped immediately in people who experience unexplained bruising, severe fatigue, or decreased urination.

Consult a healthcare provider for other potential warnings and precautions.

Expert takeaway 

“In practice, convenience is one of the biggest factors when it comes to patients sticking to treatment,” says Gerardo Sison, Pharm.D., member of the SingleCare Medical Board. “Valacyclovir’s simpler dosing can be more convenient for patients, but both medications are effective options, and choosing the right one usually comes down to what works for the patient.”

Frequently asked questions about acyclovir vs. valacyclovir

Are acyclovir and valacyclovir the same?

Acyclovir and valacyclovir are closely related antiviral drugs, but valacyclovir is a prodrug of acyclovir. The body converts valacyclovir into acyclovir, which helps more of the medication get absorbed and allows for fewer daily doses.

Is acyclovir or valacyclovir better?

Both medications work well for treating infections from the herpes simplex and varicella-zoster viruses. They’re similarly effective, but valacyclovir may have the advantage of a more convenient dosing regimen and may work better for shingles-related pain. A healthcare provider can provide medical advice on the most effective drug for your condition. 

Can I use acyclovir or valacyclovir while pregnant?

Acyclovir and valacyclovir are considered safe to use during pregnancy and haven’t been found to have an increased risk of major birth defects. However, it’s important to consult a healthcare provider while pregnant or breastfeeding.

Can I use acyclovir or valacyclovir with alcohol?

There’s no direct interaction between acyclovir or valacyclovir and alcohol, but it’s still a good idea to use caution. Alcohol may cause dehydration, which can increase stress on the kidneys and increase the risk of kidney-related side effects from these antivirals. 

Which is better for shingles: Acyclovir or valacyclovir?

Both can treat shingles. However, a randomized, double-blind clinical trial found that valacyclovir resolves pain symptoms faster than acyclovir. Treatment with valacyclovir was also linked to fewer eye complications from shingles, which can be damaging and difficult to treat.

What happens if you take acyclovir and valacyclovir together?

Taking acyclovir and valacyclovir together can lead to higher concentrations of acyclovir in the body, which increases the risk of kidney problems and other side effects. Only take one antiviral at a time unless your healthcare provider specifically tells you otherwise.