Alternatives To Valtrex For The Treatment Of Herpes

In our latest question and answer, the pharmacist discusses alternatives to Valtrex for treating herpes.


Hi there. I am taking valtrex for a herpes infection, but after missing about a week of doses, the medication is not working as well. Is there any alternative to valtrex for treating herpes?

Asked by Jen On Sep 13, 2022

Answered by
Medical Content Reviewed By HelloPharmacist Staff

Published Sep 14, 2022
Last updated Sep 14, 2022

Key points

  • Oral antiviral options for treating herpes include Zovirax (acyclovir), Valtrex (valacyclovir), and Famvir (famciclovir).
  • All three oral antivirals are similarly effective but are dosed differently.
  • There are topical options for treating herpes, and they include Zovirax (acyclovir) ointment/cream and Denavir (penciclovir). Topical therapies are generally not as effective as oral therapies and need to be dosed often.
  • Drug resistance to oral antiviral options for herpes is uncommon unless you have a condition that affects your immune system (e.g. HIV). Alternative options for those with true drug resistance and who have a compromised immune system include foscarnet and cidofovir (both intravenously administered).

Thanks for reaching out to us!

There are three oral therapies used to treat herpes infections:

  • Valtrex (valacyclovir)
  • Zovirax (acyclovir)
  • Famvir (famciclovir)

Studies show that all three of these drugs have similar effectiveness, but there are some subtle differences, including how they are dosed.

Oral Therapy Options For Acute And Chronic Treatment

Now, you don't mention in your question if you are currently taking Valtrex chronically (as a preventative) or for an acute attack. You also don't mention if you are treating herpes simplex virus 1 or 2.

Although an oversimplification, herpes simplex virus 1 (HSV-1) is commonly referred to as 'oral herpes' and causes cold sores. Herpes simplex virus 2 (HSV-2) is sexually transmitted and causes both oral and genital herpes sores.

Below, I list the CDC recommended dosing for each of the oral therapy options below for each situation.

Acute Treatment (HSV-2)

  • Acyclovir: 800 mg three times daily for two days; or 800 mg twice daily for five days
  • Famciclovir: 1000 mg twice daily for a single-day duration; or 125 mg twice daily for five days; or 500 mg once, followed by 250 mg twice daily for two days
  • Valacyclovir: 500 mg twice daily for three days or 1000 mg once daily for five days

Chronic Infection Treatments (HSV-2)

  • Acyclovir: 400 mg twice daily
  • Famciclovir: 250 mg twice daily
  • Valacyclovir: 500 mg once daily or 1000 mg once daily

Acute Treatment (HSV-1)

  • Acyclovir: 400 mg orally three times daily or 200 mg five times daily for 7 to 10 days
  • Famciclovir: 250 mg three times daily or 500 mg twice daily for 7 to 10 days
  • Valacyclovir: 1 g twice daily for 7 to 10 days

How Treatments Compare

As mentioned, in terms of effectiveness, studies show all three drugs are relatively similar.

Some studies suggest valacyclovir may be slightly better in terms of shortening the time to heal versus famciclovir, as one concluded the following:

Valacyclovir appear to be somewhat better than famciclovir for suppression of genital herpes and associated shedding. Further comparative trials of antiviral drugs for various indications should be performed as acyclovir and penciclovir appear to have different ability to abrogate HSV reactivation.

In clinical practice, valacyclovir is generally preferred over other treatments due to its ease of dosing and effectiveness.

Topical Therapy Options

Topical options (i.e. drugs that are applied to the skin) include Zovirax (acyclovir) cream/ointment and Denavir (penciclovir). Abreva is also available over the counter.

In general, topical options aren't recommended over oral options since studies show they are less effective than oral antiviral therapy and have to be applied multiple times daily to be effective.

Nevertheless, they are an option for those who prefer not to use oral therapies or if there is a specific medical reason why cannot be used. There is a small chance too that they can provide additional benefit after using oral therapies.

Failed Valtrex?

As written above, in terms of oral antiviral options, there are three.

If Valtrex (valacyclovir) has become ineffective, that leaves acyclovir and famciclovir. However, valacyclovir is converted in the body to acyclovir, and the assumption would be that if valacyclovir no longer works well, neither would acyclovir. That leaves you with famciclovir. Topical therapies, although likely less effective, are options too.

However, dosing is important for oral therapies.

If you failed valacyclovir at the 500mg dose, you may find more benefit with the 1,000mg daily dose. Some studies show that is more effective than the 500mg dose taken twice a day.

Lastly here, I do want to mention that unless you have a concurrent disease that compromises your immune system (e.g. HIV), drug resistance to acyclovir and related antivirals is quite uncommon. Studies investigating the matter put the rate of true drug resistance at less than 0.5% of individuals who are not immunocompromised.

There are some drugs used in those who are truly drug-resistant and have a concurrent disease that weakens the immune system (e.g. HIV). These drugs include foscarnet and cidofovir, but both are these are given intravenously are wouldn't generally be used unless the situation was severe.

Final Words

I hope this answer helped!

To wrap up, my suggestion would be to speak to your doctor about your options. First and foremost, consider the higher dose of Valtrex, and if that doesn't work, consider famciclovir. The topical options are always a possibility as well.

Reach out again anytime.


  • Resistance of herpes simplex to acyclovir, PubMed
  • Acyclovir-resistant genital herpes among persons attending sexually transmitted disease and human immunodeficiency virus clinics, PubMed
  • Comparative efficacy of famciclovir and valacyclovir for suppression of recurrent genital herpes and viral shedding, PubMed
  • Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection., PubMed
  • Drugs for non-HIV viral infections, PubMed

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Dr. Brian Staiger, PharmD

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