Valacyclovir vs Acyclovir: Differences, Dosage and Side Effects

Pharmacist or doctor taking medicines
Medically reviewed by Dr. Ola Tarabzuni

Key Takeaways

  • valacyclovir and acyclovir are effective antiviral medications for treating herpes infections.
  • valacyclovir is a prodrug of acyclovir with higher bioavailability, leading to less frequent dosing.
  • Both medications treat genital herpes, oral herpes, and shingles.
  • valacyclovir and acyclovir do not cure herpes but can help manage outbreaks and reduce their frequency.
  • Neither medication is effective against other types of herpes infections caused by different viruses.


Herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections can be treated with the antiviral drugs valacyclovir and acyclovir, respectively. The prodrug valacyclovir increases the bioavailability of the antiviral drug acyclovir, allowing for less frequent dosing. It is effective against genital herpes, oral herpes, and shingles and comes in tablet form for easy administration.

On the other hand, acyclovir is available in various formulations but requires more frequent dosing due to lower bioavailability. Herpes outbreaks can be controlled with either medication, so the decision may come down to personal preference or other factors after discussion with a doctor.

What is Valacyclovir?

Antiviral valacyclovir is prescribed for patients with herpes simplex virus (HSV) or varicella-zoster virus (VZV) infections. As a prodrug, it undergoes internal biotransformation into the active form of acyclovir. When treating viral infections, valacyclovir is a safe and reliable option.

valacyclovir is most commonly used to treat:

  • Genital herpes, both during the acute phase of the disease and later on to prevent recurrences. 
  • In patients who have a healthy immune system, it can be used to treat herpes labialis (cold sores) and herpes zoster (shingles).
  • Valacyclovir is also given to certain organ transplant recipients to avert a cytomegalovirus (CMV) infection.

The drug works by inhibiting the viral DNA polymerase enzyme, which is essential for the replication of the herpes virus. Inhibiting viral replication and spread, valacyclovir eases symptoms, shortens the duration of outbreaks, and speeds up recovery from herpes infections.

In addition, suppressive therapy with valacyclovir can lessen the frequency of recurrent outbreaks and reduce the risk of transmission to sexual partners. Although valacyclovir is safe and effective in treating herpes infections, it may not be able to eradicate the virus if it has already lain dormant in the body. 

Which one is better acyclovir or valacyclovir? Ask an Online Doctor

What is acyclovir?

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections are commonly treated with acyclovir, an antiviral medication. Due to its efficacy and relative safety, it has become a staple in treating viral infections despite being one of the earliest and most commonly prescribed antiviral drugs.

acyclovir is most commonly used to treat: 

  • Genital herpes, both during the acute phase of the disease and later on to prevent recurrence. 
  • Shingles (herpes zoster)
  • Cold sores (herpes labialis)
  • Chickenpox (varicella) 

Like Valacyclovir, acyclovir blocks Herpes virus replication by interfering with a viral enzyme called DNA polymerase. acyclovir helps alleviate symptoms and shorten the duration of herpes outbreaks by inhibiting the virus’s ability to reproduce and spread. However, it does not completely eliminate the virus, as herpes viruses can lie dormant and reactivate at a later time.

The medication can be taken orally in the form of tablets, topically in the form of creams, or intravenously in the case of severe cases.

Valacyclovir vs. Acyclovir?

valacyclovir and acyclovir are both antiviral medications used to treat infections caused by the herpes simplex virus (HSV) and the varicella-zoster virus (VZV). There are some differences between the two drugs, despite their shared mechanism of action and clinical applications.

The table below summarizes some differences and similarities:

Drug TypePrescription MedicationPrescription Medication
Mechanism of ActionInhibits Viral DNA replicationInhibits Viral DNA replication
Available FormsOral tabletOral tablet, injection, and cream
Strengths500mg and 1,000mgVarious strengths depending on form
Generic AvailabilityAvailable as generic and brand productAvailable as generic and brand product
Popular Use CasesShingles, genital herpes, cold sores (adults)Shingles, genital herpes, cold sores (adults) and chickenpox (children)
Approval for Pediatric UseApproved chickenpox and cold sores in Children.Approved to treat chickenpox
BioavailabilityHigher bioavailabilityLower bioavailability
Half-LifeLonger half-lifeShorter half-life
Dosage FrequencyUsually taken twice dailyUp to five doses per day (condition dependent)
Comparative Efficacy¹Small studies show no significant differenceSmall studies show no significant difference
Preferred in PracticePreferred due to less frequent dosingUsed intravenously in severe infections
Renal ClearanceLess dependent on renal clearanceMore dependent on renal clearance in older adults with CKD

To elaborate on some of the major differences please see the detail below:


Since valacyclovir is a prodrug of acyclovir, it must be metabolized in the body to produce the active form (acyclovir). With valacyclovir, you can get more acyclovir into your system than with regular acyclovir tablets because of this conversion. Due to valacyclovir’s enhanced bioavailability, it is possible to treat viral infections with lower doses than would be required with acyclovir.

Dosage Frequency

Due to its enhanced bioavailability, valacyclovir is typically dosed less frequently than acyclovir. For example, in treating genital herpes outbreaks, acyclovir is often taken five times a day, while valacyclovir is taken only twice daily. This reduced dosing frequency can improve patient compliance and convenience.


When it comes to treating Herpes virus infections, both valacyclovir and acyclovir work well. Some research, however, suggests that valacyclovir, as opposed to acyclovir, may result in more rapid symptom resolution and a shorter recovery time. This possible benefit is likely attributable to the higher acyclovir levels achieved when taking valacyclovir.

Dosage strength of Valacyclovir

Herpes Simplex Virus (HSV) Outbreaks

For the treatment of initial genital herpes, the usual recommended dose of valacyclovir (Valtrex) is 1,000 mg (one 1,000 mg tablet) taken twice daily for 7-10 days. For recurrent genital herpes, the recommended dose is 500 mg (one 500 mg tablet) taken twice daily for 3-5 days.

Herpes Zoster (Shingles)

The typical dosage of valacyclovir (Valtrex) is 1,000 mg (one 1,000 mg tablet) taken three times daily for seven days.

Suppression of Recurrent Genital Herpes

For chronic suppression of recurrent genital herpes, the usual dose of valacyclovir is 500 mg (one 500 mg tablet) taken once daily.

Acyclovir Dosage Strength

Herpes Simplex Virus (HSV) Outbreaks and acyclovir

For the treatment of initial genital herpes, the typical dose of acyclovir (Zovirax) is 200 mg (one 200 mg tablet) taken five times daily for 7-10 days. For recurrent genital herpes, the usual dose is 400 mg (two 200 mg tablets) taken three times daily for five days.

Herpes Zoster (Shingles)

The recommended dose of acyclovir (Zovirax) is 800 mg (one 800 mg tablet) taken five times daily for 7-10 days.

Suppression of Recurrent Genital Herpes

For chronic suppression, the usual dose of acyclovir (Zovirax) is 400 mg (two 200 mg tablets) taken twice daily.

Which drugs or food should I avoid while taking valacyclovir or acyclovir? 

Drugs that are nephrotoxic or hepatotoxic can be hazardous if taken in combination with acyclovir and valacyclovir. These drugs that may interact with acyclovir and valacyclovir include the following:

  1. Theophylline
  2. Tenofovir
  3. Foscarnet
  4. Mycophenolate
  5. Any dose of valacyclovir and acyclovir must be avoided if you had a shot of live attenuated vaccines recently.
  6. Other drugs that are contraindicated with these anti-virals include:
  • Mannitol
  • Foscarnet
  • Capreomycin
Is valacyclovir equivalent to acyclovir? See an Online Doctor

Foods to Avoid

When taking acyclovir or Valacyclovir, there are no dietary restrictions. However, both drugs are known to be hepatotoxic and nephrotoxic therefore it’s essential to maintain a healthy and balanced diet to support your overall well-being and immune system during treatment. 

Here are some general dietary recommendations:

Stay Hydrated

It is especially important for those with impaired kidney function to drink plenty of water while taking these drugs. Keep your kidneys and body healthy by drinking water frequently throughout the day.

Avoid Alcohol

While on acyclovir or valacyclovir, you should cut back or abstain completely from alcohol. Drugs like these antivirals are metabolized by the liver, which can be further taxed by alcohol consumption. There may be an increase in liver-related side effects if alcohol is consumed while taking these medications.

Eat a Nutrient-Rich Diet

Diets that lack variety are less likely to be healthy, so make sure you’re getting plenty of fruits, veggies, whole grains, lean proteins, and healthy fats. A healthy, nutrient-rich diet can help speed up the healing process by bolstering your immune system and general health.

Manage Trigger Foods

Herpes labialis (cold sores) can be prevented by avoiding certain nuts, chocolate, citrus fruits, and foods high in arginine (an amino acid that may trigger cold sore outbreaks in some people). Some people have found that avoiding these foods helps prevent herpes outbreaks, though there is not much evidence to support this.

Practice Good Food Safety

Follow safe food handling procedures to avoid getting sick from tainted food and further burdening your weakened immune system.

Remember that everyone has slightly different dietary requirements and preferences, so it’s best to find and stick to a diet that works for you while still paying attention to general healthy eating guidelines. Make sure your diet is working in harmony with your medical treatment by discussing any dietary concerns or restrictions with your doctor or a registered dietitian.

Valacyclovir vs. acyclovir side effects

Both valacyclovir and acyclovir are generally well-tolerated medications, but like any drug, they can cause side effects. Side effects can vary in frequency and intensity and may not occur at all or only in a minority of people taking the drug.

The table below summarizes the common and uncommon side effects for both acyclovir and valacyclovir:

Side Effectsvalacyclovir (Valtrex)acyclovir
Common Side EffectsRashRash
Abdominal painAbdominal pain
Serious Side EffectsAllergic reactionsAllergic reactions
– Rash– Rash
– Itching– Itching
– Swelling of face, lips, or tongue– Swelling of face, lips, or tongue
– Severe dizziness– Severe dizziness
– Difficulty breathing– Difficulty breathing
Unusual changes in urine outputUnusual changes in urine output
– Sign of kidney problems– Sign of kidney problems
Mental/mood changes– N/A (Rarely associated with)
– Agitation
– Hallucinations
– Confusion
Signs of low platelet countSigns of low platelet count
– Easy bruising– Easy bruising
– Bleeding– Bleeding

If you take either of these drugs and experience serious or ongoing negative effects, you should see a doctor right away.

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FAQs About Azithromyin for Chlamydia

Can valacyclovir and acyclovir treat all forms of herpes?

Yes, valacyclovir and acyclovir can effectively treat symptoms of Herpes Simplex virus (HSV) infections (genital and oral herpes) and Varicella-zoster virus (VZV) infections (chickenpox and shingles).

Are acyclovir and valacyclovir the same drug?

Acyclovir and valacyclovir are not the same but they are very similar because valacyclovir is a prodrug of acyclovir. Herpes virus infections can be treated with either one.

Does valacyclovir clear up herpes?

No, valacyclovir is effective in reducing the frequency and severity of herpes outbreaks, it does not eradicate the virus entirely because it can lie dormant in the body.

How long after taking valacyclovir or acyclovir does herpes go away?

valacyclovir is known to provide relief within 2-3 days after taking it while acyclovir takes about 5-10 days to treat the viral infection after administration of the first dose.

Can I take acyclovir or valacyclovir if I am pregnant or breastfeeding?

Yes, whether pregnant or breastfeeding, acyclovir and valacyclovir are considered safe to use.

Can you drink alcohol while taking acyclovir?

It is usually best to avoid alcohol while taking any medication as these medications cause liver damage and constant or overuse of alcohol also leads to the same.

What happens if you take acyclovir and valacyclovir together?

It can accelerate side effects and can cause kidney damage if taken together.

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