Acyclovir and valacyclovir are two of the most commonly prescribed antiviral medications used to treat herpes viral infections. But what’s the difference between these two drugs, and is one better than the other? Here’s an in-depth look at how acyclovir and valacyclovir compare in terms of uses, effectiveness, side effects, cost, and other key factors.
Uses of Acyclovir and Valacyclovir
Acyclovir and valacyclovir are primarily used to treat infections caused by the herpes simplex virus (HSV). This includes genital herpes and oral herpes (cold sores). Both medications can shorten the duration of outbreaks, prevent recurrent outbreaks, and reduce transmission risk.
The main uses of acyclovir and valacyclovir include:
- Treatment of initial genital herpes outbreaks
- Suppression of recurrent genital herpes episodes
- Reduction of transmission risk in discordant couples where one partner has genital herpes [1]
- Treatment of herpes infections of the skin, lips, mouth, and other areas
- Management of initial oral herpes outbreaks and recurrences
- Decreasing frequency of oral herpes episodes
- Treatment of varicella zoster virus (herpes zoster or shingles)
- Treatment of chickenpox
- Management of uncomplicated herpes infections in immunocompromised patients
Acyclovir and valacyclovir are also sometimes prescribed “off-label” for conditions like herpes simplex encephalitis, Bell’s palsy, and herpes gladiatorum. For FDA-approved indications, acyclovir and valacyclovir are equally recommended as first-line oral antiviral therapy.
[1] https://www.ncbi.nlm.nih.gov/books/NBK544269/
Mechanisms of Action
Acyclovir and valacyclovir work in the same way. They are both prodrugs that get converted by the body into active forms that work to halt replication of the herpes virus.
Specifically, acyclovir is metabolized into its active form called acyclovir triphosphate. Valacyclovir gets converted into acyclovir as its active metabolite.
These active metabolites act as nucleoside analog DNA polymerase inhibitors. They selectively block viral DNA synthesis by viral thymidine kinase, which inhibits replication of viral DNA and stops the virus from proliferating further [2].
So while taken as different prodrugs, acyclovir and valacyclovir share the same mechanism of action as they both ultimately work by enhancing the cellular production of acyclovir triphosphate. This active metabolite has direct antiviral properties against the herpes virus.
[2] https://www.ncbi.nlm.nih.gov/books/NBK544269/
Effectiveness for Herpes Outbreaks
Numerous clinical studies have proven both oral acyclovir and valacyclovir to be highly effective for managing outbreaks and recurrences of genital herpes and oral herpes. Some key findings on their efficacy:
- A meta-analysis in the Journal of the American Medical Association found that acyclovir significantly accelerated lesion healing time and decreased recurrence for genital herpes outbreaks [3].
- Research published in Cutis showed that both acyclovir and valacyclovir reduced the duration of viral shedding by 1-2 days during initial genital herpes episodes [4].
- A study in the Journal of Infectious Diseases determined that valacyclovir was at least as effective as acyclovir for reducing the severity and duration of oral herpes outbreaks [5].
- Clinical trials demonstrate that both drugs decrease pain, itching, lesions, and time to complete healing for oral and genital herpes recurrences [6].
- When started early, acyclovir and valacyclovir can shorten first outbreaks by 2-4 days typically. Both drugs reduce recurrence rates by 50% or more in many patients [7].
Based on multiple head-to-head trials, acyclovir and valacyclovir are considered equally effective for managing active herpes outbreaks and providing long-term suppressive therapy.
[3] https://jamanetwork.com/journals/jama/fullarticle/372258
[4] https://pubmed.ncbi.nlm.nih.gov/2972747/
[5] https://academic.oup.com/jid/article/169/1/92/839134
[6] https://www.aafp.org/afp/2011/1115/p1003.html
[7] https://www.cdc.gov/std/herpes/stdfact-herpes-detailed.htm
Suppressive Therapy
Both valacyclovir and acyclovir can be used as daily suppressive therapy to prevent recurrent outbreaks in patients with frequent recurrences of oral or genital herpes.
Typical dosing for suppressive therapy:
- Valacyclovir – 500 mg once daily
- Acyclovir – 400 mg twice daily
Results from clinical trials on their suppressive effects:
- A study in Sexually Transmitted Diseases found acyclovir and valacyclovir equally reduced recurrence rates and extended the time to first recurrence [8].
- Research in the Journal of Medical Virology showed long-term valacyclovir and acyclovir therapy for 1 year significantly decreased genital lesion rates and viral shedding [9].
- A trial in Oral Surgery, Oral Medicine, Oral Pathology determined valacyclovir taken for 6 months almost completely eliminated recurrences of oral herpes [10].
- Multiple studies report at least 75% of patients on daily valacyclovir or acyclovir experience a marked reduction in outbreaks and many patients remain recurrence-free [11].
For long-term suppression of herpes simplex outbreaks, acyclovir and valacyclovir seem essentially equivalent in efficacy and patient satisfaction based on the data.
[8] https://pubmed.ncbi.nlm.nih.gov/10796570/
[9] https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.10548
[11] https://www.aafp.org/afp/2002/1201/p2117.html
Side Effects and Safety
Both valacyclovir and acyclovir are generally very safe and well-tolerated antiviral medications when used as prescribed. Most side effects are mild. Common adverse effects may include:
- Headache
- Nausea
- Stomach pain
- Diarrhea
- Dizziness
- Rash
Acyclovir is associated with a slightly higher risk of gastrointestinal side effects like nausea and vomiting. Valacyclovir also has a lower potential for central nervous system side effects such as headache, hallucinations, and confusion according to an analysis of adverse events data [12].
Rare but serious side effects can occur. Seek prompt medical care if you experience:
- Signs of kidney dysfunction like lower back pain, changes in urination, swelling
- Unusual bruising or bleeding
- Problems with speech or vision
- Difficulty breathing
- Fever or chills
Talk to your doctor about any side effects. Dosage reductions or alternative medications may be warranted in some cases if adverse effects become bothersome. Don’t double your dosage if you miss a dose.
[12] https://www.ncbi.nlm.nih.gov/books/NBK459259/
Interactions With Other Drugs
Acyclovir and valacyclovir have relatively few medication interactions. But important potential interactions to discuss with your doctor include:
- Nephrotoxic drugs like cyclosporine that can further damage kidneys
- Mycophenolate mofetil which may need dose reduction
- Probenecid that may impact excretion leading to higher antiviral levels
- Antacids and multivitamins that can decrease absorption if taken at the same time
No major metabolism issues occur as acyclovir and valacyclovir are excreted unchanged in urine. But the dose may need lowering if there is kidney impairment. Avoid use if there is significant kidney dysfunction.
Dosage Forms Available
Acyclovir is available in:
- Capsule form (200 mg, 400 mg, 800 mg)
- Tablet form (400 mg, 800 mg)
- Suspension form (200 mg/5 mL)
- Intravenous injection formula for severe cases
Valacyclovir is available in:
- 500 mg and 1,000 mg tablets typically
Valacyclovir has an advantage of only being taken 1-2 times a day typically, compared to acyclovir’s often 5 times daily dosing. But acyclovir does come in an intravenous version for hospitalized patients. Both drugs are available as generic products to help reduce cost.
Cost Comparison
Generic valacyclovir typically costs significantly more than generic acyclovir. According to data from the Health Care Cost Institute, generic valacyclovir costs over 3 times more per unit than generic acyclovir [13].
Some example costs for a 30 day supply:
- Generic valacyclovir 500 mg tablets: $15-$45
- Generic acyclovir 400 mg tablets: $10-$15
Valacyclovir tends to be prescribed more often despite the higher cost because its prodrug formulation leads to higher levels of acyclovir in the body. The less frequent dosing schedule also promotes better adherence. However, acyclovir costs less for economically concerned patients.
Some insurance plans also still favor valacyclovir over acyclovir due to fewer daily doses. But others are starting to switch preferences to acyclovir to reduce expenses. Check your specific medication coverage and out-of-pocket costs.
[13] https://healthcostinstitute.org/images/pdfs/HCCI_Acyclovir_Valacyclovir_IB.pdf
Patient Satisfaction and Adherence
In patient surveys, both antivirals receive high marks. However, valacyclovir performs a bit better in terms of convenience and adherence.
In one questionnaire study published in Clinical Drug Investigation, patients rated valacyclovir 9.5 out of 10 for ease of use compared to only 8.2 for acyclovir [14]. The less frequent daily dosing schedule of valacyclovir increases satisfaction.
Research in PharmacoEconomics found compliance rates with long-term suppressive acyclovir therapy averaged only about 65%. For valacyclovir, adherence for chronic use exceeded 80% [15]. The simpler regimen again explains the difference.
While both provide effective relief, patients seem to prefer valacyclovir’s easier dosing. However, acyclovir remains a good option for cost-conscious individuals willing to take multiple daily doses.
[14] https://link.springer.com/article/10.2165/00044011-200632050-00003
[15] https://link.springer.com/article/10.2165/00019053-200622050-00004
Conclusion: Which Is Better – Acyclovir or Valacyclovir?
In summary, acyclovir and valacyclovir have the same mechanism of action and are equally effective for treating and preventing herpes simplex viral infections. The main differences come down to dosing frequency, cost, and adherence.
Valacyclovir advantages:
- Taken only 1-2 times a day typically – Better adherence
- Higher levels of active drug with smaller doses
- Well absorbed even without food
- Considered more convenient overall
Acyclovir advantages:
- Taken 2-5 times daily – Inconvenient for some
- Generic available – Much cheaper cost
- Intravenous formulations available
- Similar efficacy to valacyclovir for many patients
For cost-sensitive patients who don’t mind multiple daily doses, traditional acyclovir remains a viable lower-cost option. However most doctors and patients today prefer valacyclovir for its simpler dosing, better adherence, and enhanced absorption profile despite the higher price.
Talk to your doctor about whether generic acyclovir or brand-name valacyclovir is the right choice for treating or suppressing your herpes simplex viral infections.
