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Acyclovir side effects and how to avoid them

Common acyclovir side effects include nausea, vomiting, diarrhea, and malaise. Here's how to avoid them.

Common acyclovir side effects | Nausea & vomiting | Diarrhea | Malaise | Injection site reactions | Serious side effects | Anaphylaxis | Stevens-Johnson syndrome | Kidney damage | How long do side effects last? | Warnings | Interactions | How to avoid side effects

Acyclovir, also known by GlaxoSmithKline’s brand name Zovirax, is a prescription antiviral medication approved by the U.S. Food and Drug Administration (FDA) to treat herpes zoster infections (shingles), recurrent cold sores, chickenpox, and genital herpes. Acyclovir is available as tablets, capsules, liquid suspension, intravenous (IV) injection, and as a cream for topical use. It also comes as a buccal tablet, under the brand name Sitavig, that dissolves in the mouth.

Acyclovir is a member of a class of drugs called synthetic nucleoside analogues. It works by interfering with the viral replication of the herpes viruses. Although it is not a cure for herpes infections, acyclovir decreases the severity and length of the herpes virus outbreaks.

As with any medication, it is important to be aware of adverse effects and drug-drug interactions before beginning therapy. The following drug information highlights potential acyclovir side effects and how to avoid them.

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Common side effects of acyclovir

The most common side effects of acyclovir include:

  • Nausea
  • Vomiting
  • Diarrhea
  • Headache
  • Malaise (general weakness or discomfort)
  • Feeling dizzy
  • Arthralgia (joint pain)
  • Rash
  • Lethargy
  • Confusion
  • Agitation
  • Photosensitivity (hypersensitive to exposure to sunlight)

Side effects may vary depending on the form of acyclovir you use.

Other common acyclovir side effects

Form of acyclovir Other side effects
IV infusion
  • Injection site reactions (inflammation, phlebitis)
  • Elevations in blood urea nitrogen (BUN) or serum creatinine 
Topical cream
  • Dry lips
  • Desquamation (shedding outer layer of skin)
  • Dryness of skin
  • Cracked lips
  • Burning skin
  • Pruritus (itching)
  • Flakiness of skin
  • Stinging on skin
Buccal tablets
  • Pain at the gum site
  • Aphthous stomatitis (canker sores)

These are not all the possible side effects of acyclovir. For more information regarding side effects talk to your healthcare professional.

Nausea and vomiting

In genital herpes clinical studies, 2.7% of patients reported nausea and/or vomiting during short-term treatment (10 days of therapy) and 4.8% of patients reported nausea in long-term treatment (12 months of therapy). In clinical trials involving IV infusion, nausea and/or vomiting were reported by 7% of patients.

Diarrhea 

Diarrhea was the most frequent adverse event seen in the chickenpox clinical studies with 3.2% of patients.

Malaise

The most frequent adverse event reported during the herpes zoster (shingles) clinical trials was malaise (11.5%), although 11.1% of the participants receiving placebo, or sugar pills, also reported malaise.

Injection site reactions

The most frequent adverse events seen in patients receiving the IV infusion of acyclovir during clinical trials was inflammation at the injection site or phlebitis (inflammation of the walls of the vein) at 7%.

Serious side effects of acyclovir

Acyclovir may cause the following rare, but serious side effects:

  • Anaphylaxis (severe allergic reaction)
  • Stevens-Johnson syndrome
  • Kidney failure
  • Hallucinations
  • Psychosis
  • Encephalopathy (damage or disease that affects the brain)
  • Seizures
  • Coma
  • Leukopenia (a reduction in the number of white cells in the blood)
  • Thrombocytopenia (deficiency of platelets in the blood)
  • Neutropenia (deficiency of neutrophils in the blood)
  • Angioedema (swelling of the tissue just under the skin) 
  • Erythema multiforme (red, raised skin areas that can appear all over the body)
  • Toxic epidermal necrolysis (a serious skin disorder characterized by a blistering and peeling of the skin)
  • Hepatitis

Anaphylaxis

Anaphylaxis, or anaphylactic shock, is a severe allergic reaction that may occur if you are hypersensitive to a drug and may require immediate medical care. Symptoms of an anaphylactic reaction may include:

  • Skin rash
  • Nausea
  • Vomiting
  • Difficulty breathing
  • Shock

Stevens-Johnson syndrome

Stevens-Johnson syndrome is a rare but severe form of allergic reaction that requires immediate medical care. Symptoms may include:

  • Flu-like symptoms
  • Painful red blisters around the mouth, throat, eyes, or genitals
  • Red or purple skin rash
  • Peeling skin
  • Fatigue
  • Diarrhea
  • Nausea and vomiting
  • Fever

Kidney damage

Antiviral drugs such as acyclovir have been known to cause acute kidney injury, particularly when administered by IV. Risk factors for developing acyclovir-induced kidney problems include hypovolemia (abnormal decrease in the volume of blood usually due to dehydration), rapid IV infusion, too high a dose of acyclovir in relation to kidney function, and simultaneous use of other drugs toxic to the kidney. Kidney toxicity has been found to occur in approximately 12% to 48% of the cases involving IV administration. The incidence of kidney damage from oral dosing of acyclovir is less clear.

Dosage adjustment is recommended when giving acyclovir to patients with kidney impairment or who are also on other medicines that may be toxic to the kidney since this may increase the risk of kidney dysfunction, particularly when using IV acyclovir. 

How long do acyclovir side effects last?

Most side effects of acyclovir that occur usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. However, if you have an allergic reaction you should notify your healthcare professional immediately. 

Acyclovir contraindications and warnings

  • Acyclovir should not be taken by anyone hypersensitive to any active or inactive ingredient or Valtrex (valacyclovir), which is a similar antiviral medication. 
  • Other medical conditions may affect how acyclovir affects you, specifically:
    • If you are dehydrated or have kidney disease it may increase blood levels of acyclovir, increasing the chance of side effects.
    • If you have nervous system problems, acyclovir may make these problems worse.
  • Acyclovir cream should only be applied on the external affected areas of the lips and face in patients with cold sores and not in the eye or inside the mouth or nose.
  • Acyclovir for injection is intended for IV use only and should not be used topically, orally, on the skin, or in the eye.

Abuse and dependence

Acyclovir is not habit-forming or addictive, and there are no withdrawal symptoms associated with discontinuing acyclovir. 

Missed dose

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of acyclovir at the same time.

Overdose

Oral overdoses involving ingestion of up to 100 capsules (equal to 20 grams) have been reported. Adverse events reported with overdose include agitation, coma, seizures, and lethargy. You should report any overdose situation to your healthcare professional.

Overdosage has been reported following inappropriately high doses given to patients by IV infusion whose fluid and electrolyte balance were not properly monitored. This has resulted in elevated blood urea nitrogen (BUN) and serum creatinine levels causing kidney failure. Lethargy, convulsions, and coma have been reported. Overdose patients may require hemodialysis until kidney function is restored.

Overdose events using acyclovir cream topically are unlikely because there is very little absorption into the bloodstream.

Pregnancy and breastfeeding

There are no adequate and well-controlled clinical studies in pregnant women. Use acyclovir during pregnancy only if the potential benefit outweighs the risk. This drug has been found in breast milk following oral administration. Nursing mothers should take it with caution and only when the potential benefit outweighs the risk. A woman’s healthcare provider is the best source of information when considering the use of acyclovir while pregnant or breastfeeding.

Acyclovir interactions

Taking acyclovir with any of the following medicines is not recommended:

  • Arava (leflunomide)
  • Aubagio (teriflunomide)
  • Foscavir (foscarnet)
  • Valtrex (valacyclovir)
  • Vistide (cidofovir)

Taking acyclovir with any of the following medicines may cause an increased risk of side effects:

  • Dilantin (phenytoin)
  • Depakene (valproic acid)
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen or naproxen

This is not a comprehensive list and other drugs may interact with acyclovir including prescription drugs as well as nonprescription products such as over-the-counter medicines, vitamins, and herbal products. Consult your healthcare professional for professional medical advice regarding medicines to avoid while taking acyclovir.

How to avoid acyclovir side effects

1. Carefully read the patient information you receive

Carefully read the patient information you receive about the treatment of herpes, chickenpox, or shingles before using acyclovir. Acyclovir is best used as soon as possible after the symptoms of chickenpox, herpes, or shingles appear (for example, pain, burning, or blisters).

2. Discuss kidney health with your provider

Tell your healthcare professional if you have or have had kidney problems, as acyclovir can cause kidney injury.

3. Follow all instructions for taking acyclovir

It is important to keep taking acyclovir for the full time of treatment as directed by your healthcare professional even if your symptoms begin to clear up after a few days. 

When taking oral acyclovir:

  • You may take oral acyclovir without regard to meals. 
  • When using acyclovir oral suspension use a measuring spoon to measure each dose accurately.

When using acyclovir buccal tablets:

  • Use within one hour after you have the first symptom of a cold sore, such as itching, redness, burning, or tingling, and before a cold sore appears.
  • Apply the tablet to your upper gum, just above your incisor tooth, on the same side of your mouth as the cold sore symptoms.
  • You may eat and drink while using the tablet.
  • Do not crush, chew, suck, or swallow the buccal tablet.
  • Leave the tablet in place as it slowly dissolves over time while in your mouth.
  • If the tablet does not stick to your upper gum or falls off of your upper gum within the first six hours after you apply it, the same tablet should be placed back onto your upper gum right away.
  • Gently rinse your mouth with water to clean your teeth while the tablet is in place.
  • Drink more liquids if your mouth becomes dry while using the tablet.
  • If you swallow the tablet within the first six hours of applying it, drink a glass of water and place a new tablet onto your upper gum.

When using acyclovir cream: 

  • Wash hands prior to application and ensure the face and/or lips are clean and dry. 
  • Apply enough acyclovir cream to cover the affected area including the outer margin.
  • Avoid unnecessary rubbing of the affected area to avoid aggravating the infection.
  • Wash hands with soap and water after using acyclovir cream.

4. Hydrate while taking acyclovir

It is important to take acyclovir with a full glass of water and to drink plenty of liquids during therapy to avoid becoming dehydrated.

5. Know when to contact a healthcare professional

If your symptoms do not improve within a few days of starting acyclovir treatment, or if they become worse, contact your healthcare professional.