acyclovir vs valacyclovir

PlainMeds reviewed this comparison against our methodology in August 2026. It places FDA and CMS record fields side by side, without recommending either medication.

Side-by-side comparison of acyclovir and valacyclovir. Data from FDA drug databases (Orange Book, NDC Directory, recalls, shortages) covering 20,000+ approved drugs, plus CMS pricing; see our methodology.

Drug Class
acyclovir Antiviral (Nucleoside Analog)
valacyclovir Antiviral
Type
acyclovir Prescription
valacyclovir Prescription
Summary
acyclovir

Acyclovir is an antiviral medicine. It is used to treat infections caused by certain viruses.

valacyclovir

Valacyclovir is an antiviral medicine. It is used to treat infections caused by certain viruses.

What It Treats
acyclovir

Acyclovir is used to treat shingles, which is caused by herpes zoster. It also treats genital herpes, both the first time you have it and when it comes back. Acyclovir can also treat chickenpox.

valacyclovir

Valacyclovir treats cold sores, genital herpes, and shingles. For genital herpes, it can treat initial outbreaks, repeat outbreaks, and also prevent outbreaks. It can also lower the chance of spreading genital herpes to others.

How It Works
acyclovir

Acyclovir stops the virus from growing and spreading. It does this by interfering with the virus's ability to make copies of itself. This helps your body fight off the infection.

valacyclovir

Valacyclovir stops the virus from growing and spreading. It does this by blocking a key enzyme the virus needs to reproduce. This helps your body fight off the infection.

Common Side Effects
acyclovir
  • Malaise (feeling unwell)
  • Nausea
  • Diarrhea
valacyclovir
  • Headache
  • Nausea
  • Abdominal pain
FAERS Reports
acyclovir
  • Fatigue 7,612
  • Diarrhoea 7,064
  • Pneumonia 5,471
  • Nausea 5,328
  • Pyrexia 4,719
valacyclovir
  • Fatigue 2,294
  • Diarrhoea 2,120
  • Nausea 1,838
  • Febrile Neutropenia 1,545
  • Pyrexia 1,490
Serious Warnings
acyclovir

Acyclovir can cause nervous system problems, especially in older adults or people with kidney problems. Tell your doctor if you have kidney problems before taking this medicine.

valacyclovir

Valacyclovir can cause serious problems like TTP/HUS, which is a blood disorder. This is more likely in people with advanced HIV or who have had bone marrow or kidney transplants, especially if they take high doses (8 grams per day). It can also cause kidney failure, especially in older adults or people with kidney problems. Rarely, it can cause confusion, hallucinations, or agitation. Stop taking this medicine and contact your doctor immediately if you experience any of these side effects.

Pregnancy
acyclovir

Tell your doctor if you are pregnant or plan to become pregnant. It is not known if acyclovir will harm an unborn baby. Talk to your doctor about the risks and benefits of taking acyclovir while breastfeeding.

valacyclovir

Tell your doctor if you are pregnant or plan to become pregnant. Studies haven't shown a risk of major birth defects, but there isn't enough data to be sure about miscarriage or other problems. Talk to your doctor about the risks and benefits.

Also Compare, Nearby Drugs

How to Read This acyclovir vs valacyclovir Comparison

acyclovir is classified in the Antiviral (Nucleoside Analog) drug class, while valacyclovir sits within the Antiviral class. Drugs from different classes work through distinct mechanisms, so a head-to-head comparison illustrates trade-offs rather than equivalence. Both drugs are prescription-only, so a licensed provider must authorize use.

Adverse event totals above are pulled from the FDA's Adverse Event Reporting System (FAERS). For these top-ranked reactions alone, acyclovir has 30,194 submissions while valacyclovir has 9,287. Those figures reflect cumulative reporting volume, not per-patient risk, so older, widely dispensed drugs typically look worse on count alone. No direct interaction between these two drugs is listed in our FDA-derived dataset, though co-prescription still warrants pharmacist review. Serious warnings, pregnancy guidance, and contraindications can differ even when indications overlap.

A table cannot represent individual circumstances. Data here is sourced from FDA Structured Product Labels (SPL) and FAERS, both of which update as manufacturers and clinicians submit new information. This registry does not provide medical, treatment, substitution, or medication-change directions for acyclovir or valacyclovir.

Registry boundary: This comparison displays source-record fields and does not provide individualized medical direction.