What are the side effects of oral Valacyclovir (Valacyclovir hydrochloride)?

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Last updated: May 19, 2025View editorial policy

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From the Guidelines

Valacyclovir is generally well-tolerated, with common side effects including headache and nausea, as reported in a study published in the Journal of Clinical Virology in 2012 1. When considering the potential side effects of oral valacyclovir, it is essential to weigh the benefits of treatment against the risks of adverse events.

Common Side Effects

  • Headache
  • Nausea
  • Stomach pain
  • Vomiting
  • Dizziness Some patients may also experience diarrhea or constipation.

Less Common but Serious Side Effects

These may include:

  • Unusual bleeding or bruising
  • Signs of kidney problems, such as changes in urine output
  • Extreme fatigue
  • Yellowing of eyes or skin (jaundice)
  • Mental/mood changes, such as confusion or hallucinations
  • Signs of infection, including fever or persistent sore throat Rarely, valacyclovir can cause a severe nervous system reaction called TTP/HUS, particularly in patients with weakened immune systems, which presents with confusion, seizures, and blood clotting problems, as noted in a guidelines report from the CDC, NIH, and HIV Medicine Association of the Infectious Diseases Society of America in 2009 1. Allergic reactions are uncommon but may include rash, itching, swelling, severe dizziness, or trouble breathing. These side effects vary in frequency and severity depending on dosage, treatment duration, and individual factors like kidney function and immune status. Staying well-hydrated while taking valacyclovir can help reduce the risk of kidney-related side effects. If you experience concerning symptoms while taking valacyclovir, contact your healthcare provider promptly. It is crucial to prioritize the patient's morbidity, mortality, and quality of life when considering treatment with valacyclovir, and to carefully weigh the potential benefits against the risks of adverse events. In general, the benefits of valacyclovir treatment outweigh the risks, particularly when used to treat herpes infections, as supported by the study published in the Journal of Clinical Virology in 2012 1.

From the FDA Drug Label

The most common adverse reactions reported in at least 1 indication by greater than 10% of adult subjects treated with VALTREX and observed more frequently with VALTREX compared with placebo are headache, nausea, and abdominal pain. In clinical trials for the treatment of cold sores, the adverse reactions reported by subjects receiving VALTREX 2 grams twice daily (n = 609) or placebo (n = 609) for 1 day, respectively, included headache (14%, 10%) and dizziness (2%, 1%). For the treatment of initial episodes of genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving VALTREX 1 gram twice daily for 10 days (n = 318) or oral acyclovir 200 mg 5 times daily for 10 days (n = 318), respectively, included headache (13%, 10%) and nausea (6%, 6%). For the episodic treatment of recurrent genital herpes, the adverse reactions reported by greater than or equal to 5% of subjects receiving VALTREX 500 mg twice daily for 3 days (n = 402), VALTREX 500 mg twice daily for 5 days (n = 1,136), or placebo (n = 259), respectively, included headache (16%, 11%, 14%) and nausea (5%, 4%, 5%). For the suppression of recurrent genital herpes infections, the adverse reactions reported by subjects receiving VALTREX 1 gram once daily (n = 269), VALTREX 500 mg once daily (n = 266), or placebo (n = 134), respectively, included headache (35%, 38%, 34%), nausea (11%, 11%, 8%), abdominal pain (11%, 9%, 6%), dysmenorrhea (8%, 5%, 4%), depression (7%, 5%, 5%), arthralgia (6%, 5%, 4%), vomiting (3%, 3%, 2%), and dizziness (4%, 2%, 1%).

The common side effects of oral valacyclovir include:

  • Headache
  • Nausea
  • Abdominal pain
  • Dizziness
  • Depression
  • Arthralgia
  • Vomiting 2

From the Research

Oral Valacyclovir Side Effects

  • The most common side effect of oral valacyclovir is headache, as reported in studies 3, 4.
  • High-dose prophylactic valacyclovir therapy (8 g/day) for CMV disease for prolonged periods may cause a potentially fatal thrombotic microangiopathy (TMA)-like syndrome, particularly in immunocompromised patients with advanced HIV disease 3.
  • Gastrointestinal complaints were also reported in patients receiving high-dose valacyclovir 3.
  • Valacyclovir is generally well tolerated at dosages used to suppress recurrent episodes of genital herpes (500 to 1000 mg/day) in immunocompetent and HIV seropositive individuals 3, 4.
  • Close monitoring for symptoms of TMA is indicated in all immunocompromised patients receiving high-dose valacyclovir 3.

Comparison with Other Antiviral Agents

  • Valacyclovir has a more convenient oral dosage regimen compared to aciclovir 4, 5.
  • Valacyclovir is more effective than acyclovir in reducing the duration of zoster-associated pain 4.
  • Valacyclovir is equally effective as famciclovir in hastening the healing of zoster-associated pain and PHN 5.
  • Famciclovir may be a suitable alternative for patients with acyclovir-associated renal toxicity 6, 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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