Side effects of acyclovir: a treatment for herpes

Getting diagnosed with herpes is no fun. You may be worried about how to deal with outbreaks if and when they happen, how to avoid transmitting it to other people, and the side effects of medications. In this article, we'll focus on the side effects of one of the most commonly prescribed herpes medications: acyclovir (you may know it by one of its brand names, Zovirax or Sitavig). 

There are over 80 strains of herpes viruses, but the most common types of these viral infections are oral herpes and genital herpes (caused by herpes simplex virus types 1 and 2—or HSV-1 and HSV-2), as well as shingles and chickenpox (both caused by the varicella-zoster virus). 

Acyclovir is used to treat all of these most common types of herpes viruses. Let's take a look at the side effects you might encounter on acyclovir. 

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The most common side effects of acyclovir are nausea and vomiting, but these only happen in about 2–3% of people (FDA, 2005). 

Sometimes, acyclovir is prescribed as a long-term treatment of six months or longer, specifically for people who have recurrent ocular herpes simplex (herpes of the eye) (Uchoa, 2003). With long-term use of acyclovir, nausea and vomiting are more prevalent, and headaches are a common side effect, too.

IV acyclovir side effects

Generally, acyclovir is an oral medication, but in rare and severe cases, it needs to be given intravenously. When given through an IV, some patients experience other side effects, including (FDA, 2003): 

• General discomfort or tiredness

• Pain at the injection site 

• Inflammation of the vein at the injection site (also called phlebitis)

• Elevated levels of serum creatinine and blood urea nitrogen (these are blood levels of chemicals used to estimate kidney function)

• Skin rash or itching

• Nausea and/or vomiting

Acyclovir is only given through an IV for patients who are immunocompromised, have a severe herpes outbreak, in neonatal herpes patients, or in patients with herpes simplex encephalitis (herpes in the brain). 

For nearly all other patients taking oral acyclovir, they likely won't experience any side effects more severe than nausea or vomiting. And most patients won't even have to deal with those side effects at all. 

Serious adverse effects

In extremely rare cases, acyclovir can cause more serious adverse effects. These include anemia, neutropenia (low levels of neutrophils, a type of white blood cell), thrombocytopenia (low platelet levels), thrombocytosis (excessive platelets in the blood), and Stevens-Johnson syndrome (a serious, and potentially deadly, skin disorder). These serious side effects can be quite dangerous, but they impact fewer than 1% of people. 

A very rare but deadly condition called thrombotic thrombocytopenic purpura can happen in immunocompromised patients on the IV form of acyclovir ("Acyclovir sodium," n.d.). This is a complex clotting disorder. 

So, what exactly is acyclovir? It's an antiviral medication commonly used to treat herpes virus infections, including cold sores and genital herpes. It works by preventing the herpesvirus DNA from replicating (Gnann, 1983). There are over 80 kinds of herpes viruses, but acyclovir is specifically approved to treat: 

• Oral and genital herpes, which are caused by herpes simplex virus (HSV-1 and HSV-2)

• Shingles (herpes zoster)

• Chickenpox (varicella)

It's also used to treat a rare neurological disorder called herpes simplex encephalitis. 

Other related herpes medications are valacyclovir (which converts into acyclovir in the body) and famciclovir (which is typically only used to treat shingles). See our full comparison of acyclovir, valacyclovir (brand name Valtrex), and famciclovir for more information. 

Acyclovir comes in three forms: oral, topical, and intravenous. Your healthcare provider will decide which form and dosage are appropriate for your specific condition. 

Oral acyclovir

This is the most common form of acyclovir, and it comes in a capsule or a buccal tablet (a tablet that dissolves in your cheek). Both forms should be stored at room temperature. The dosages depend on the specific condition being treated, but here are the most typical dosage situations (FDA, 2005): 

• Genital herpes—200 mg five times a day for ten days (for initial treatment), 400 mg twice a day for up to one year (for chronic suppression), and/or 200 mg five times a day for five days (started at the first sign of an outbreak). 

• Shingles (herpes zoster)—800 mg five times a day for 7–10 days. 

• Chickenpox (varicella)—800 mg four times a day for five days (for any patient that weighs over 40 kg), or in children weighing less than 40 kg, the dose is 80 mg per kilogram per day for five days. 

When used short-term to treat an acute infection or outbreak, nausea and vomiting are the most typical side effects of oral acyclovir. Still, those side effects are pretty rare. When used in long-term treatment (over six months), headache is common. 

Topical acyclovir

There are topical acyclovir treatments available for genital and oral herpes outbreaks. 

• For genital herpes, the topical treatment comes in an ointment with 5% acyclovir (NIH, 2019). It should be applied liberally to all blisters six times a day for one week. 

• A 5% acyclovir cream is used to treat oral herpes (cold sores), applied five times a day for four days (NIH, 2020). 

Both of these topical treatments can cause burning and stinging where applied, and the cream for oral herpes can also cause dry skin and lips. 

IV acyclovir

In rare cases, acyclovir needs to be administered through an IV (FDA, 2003). These are generally cases of severe infection or in patients who are immunocompromised. IV acyclovir is generally dosed based on body weight. Here are some common uses of IV acyclovir: 

• HSV-1 and HSV-2 in immunocompromised patients—In adults and adolescents, the dosage is 5 mg per kilogram every eight hours for one week. In children under 12, the dosage is 10 mg per kilogram every eight hours for one week. 

• Shingles (herpes zoster) in immunocompromised patients—Adults and adolescents get 10 mg per kilogram every eight hours for one week, while children under 12 get 20 mg per kilogram every eight hours for one week. 

• Severe initial outbreak of genital herpes—Dosed at 5 mg per kilogram every eight hours for five days. 

IV acyclovir is also used in patients with herpes simplex encephalitis and in neonatal patients with herpes simplex virus. 

In addition to nausea and vomiting that sometimes come with the standard oral treatment, IV acyclovir can also cause general discomfort, rash or itching, increased creatinine levels, and pain at the injection site. 

Acyclovir has a great safety profile, and the only people who definitely should not take it are patients who know they are hypersensitive to acyclovir or valacyclovir (a longer-acting version of acyclovir). Or, if you've had an allergic reaction to those medications, you shouldn't take acyclovir.

We don't have enough hard data to know for sure if acyclovir is safe during pregnancy, so it's generally recommended to only prescribe it in pregnant patients when the benefits far outweigh the risks. Similarly, acyclovir should only be prescribed to nursing mothers if absolutely necessary since it can pass through breast milk. Of course, as with any prescription drug, be careful to keep this medication out of reach of children. 

Patients with kidney disease or renal impairment may need to be on a lower dose of acyclovir since acyclovir gets filtered through the kidneys ("Acyclovir sodium," n.d.).

Acyclovir drug interactions

Because acyclovir gets filtered and excreted from the body through the kidneys, there are interactions with other medications that are either filtered through the kidneys or can cause other kidney problems. Examples include: 

• Certain HIV medications (including regimens containing tenofovir) 

• Some antifungal drugs and antibiotics (such as amphotericin B and gentamicin) 

• Non-steroidal anti-inflammatories (NSAIDs, such as ibuprofen and naproxen)

There are many other drugs that interact with acyclovir, some of which can increase the chance of renal failure, so be sure to discuss any medications you're currently taking with your healthcare provider ("Acyclovir sodium," n.d.).

You can take acyclovir with or without food, but be sure to drink plenty of water when taking this drug. Ask your healthcare provider if you need any clarification on side effects or other drug information for acyclovir.

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Current version

May 05, 2021

Written by

Rachel Honeyman

Fact checked by

Mike Bohl, MD, MPH, ALM

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About the medical reviewer

Mike Bohl, MD, MPH, ALM

Dr. Mike is a licensed physician and a former Director, Medical Content & Education at Ro.