Do valacyclovirs make you tired? A Comprehensive Guide to Antiviral-Induced Fatigue

October 10, 2025 •

4 min read

According to clinical trial data, fatigue was reported as an adverse reaction in 8% of HIV-1-infected subjects taking valacyclovir, compared to 5% in the placebo group. This indicates that, for some individuals, do valacyclovirs make you tired is a question answered affirmatively, though the frequency can vary.

Quick Summary

This article details the potential connection between valacyclovir and fatigue. It covers the prevalence of this side effect, explores possible causes, identifies risk factors, and offers guidance on management and when to seek medical advice.

Key Points

Fatigue is a Known Side Effect: Clinical data confirms fatigue as a possible adverse reaction, especially in immunocompromised individuals like those with HIV.
Risk Factors Increase Susceptibility: Individuals who are elderly, have renal impairment, or compromised immune systems are at a higher risk of experiencing fatigue from valacyclovir.
Hydration and Sleep are Key: Proper hydration helps prevent dehydration-related side effects, and maintaining a consistent sleep schedule can help manage tiredness.
Tiredness Can Indicate Serious Complications: While often mild, severe fatigue combined with other symptoms like decreased urination could be a sign of kidney problems, requiring immediate medical attention.
Consult a Doctor for Management: If fatigue is bothersome, a healthcare provider can help determine the cause, suggest lifestyle changes, or potentially adjust the dosage.
Similar to Acyclovir, but Dosing Differs: As a prodrug of acyclovir, valacyclovir has a similar side effect profile but requires less frequent dosing due to better absorption.

Valacyclovir and the Likelihood of Fatigue

Valacyclovir, the active ingredient in Valtrex, is an antiviral medication used to treat various herpes virus infections, including shingles, genital herpes, and cold sores. While often well-tolerated, fatigue is a potential side effect, though it is not one of the most common reported in the general immunocompetent population.

Clinical data, particularly concerning immunocompromised individuals, provides insight into the drug's link to tiredness. For example, in studies of HIV-1-infected subjects, 8% of participants on a valacyclovir regimen reported fatigue, compared to 5% on a placebo. While this may not be a high percentage, it confirms that the medication can induce fatigue. User-reported experiences also list fatigue as a side effect. It is important to remember that these are user-submitted accounts and are not clinically verified like the FDA drug label findings.

How Antivirals May Cause Tiredness

While the precise mechanism by which valacyclovir causes fatigue is not explicitly stated, some potential explanations exist. Valacyclovir is a prodrug of acyclovir, meaning it's converted into the active antiviral compound within the body. Its action involves inhibiting viral DNA synthesis. It is theorized that the body's response to the drug or its effects on cellular metabolism and immune function could contribute to a feeling of tiredness. Additionally, the underlying viral infection itself can cause fatigue, making it challenging to pinpoint the exact cause of the symptom.

Risk Factors for Valacyclovir-Related Fatigue

Several factors can increase a person's risk of experiencing fatigue or other side effects while taking valacyclovir:

Compromised Immune Systems: Individuals with a weakened immune system, such as those with HIV or who have had a bone marrow transplant, are at higher risk for side effects like fatigue.
Renal Impairment: Because the kidneys are responsible for clearing valacyclovir from the body, reduced kidney function can lead to an accumulation of the drug. This can increase the risk of both general fatigue and more serious complications, and may require a dose adjustment.
Advanced Age: Elderly patients are more susceptible to central nervous system side effects, including agitation and confusion, which can also manifest as or contribute to a feeling of extreme tiredness.
Dehydration: Inadequate hydration can exacerbate kidney issues and other side effects, making it crucial to drink plenty of fluids while on this medication.

Managing Fatigue While Taking Valacyclovir

If you experience fatigue while on valacyclovir, several strategies may help manage the symptom. However, it is essential to consult a healthcare provider, especially if the tiredness is severe or persistent.

Here are some tips for managing mild to moderate fatigue:

Stay Hydrated: Drinking plenty of fluids, particularly water, helps support kidney function and can prevent dehydration, which might worsen fatigue.
Maintain a Consistent Sleep Schedule: Poor sleep can trigger or worsen feelings of tiredness. Prioritizing consistent, good-quality sleep is crucial.
Take with Food: For some, taking the medication with food can help alleviate stomach discomfort, which can indirectly impact energy levels.
Monitor and Track: Keeping a log of when the fatigue occurs and its severity can help identify patterns or triggers. This information is valuable for a healthcare provider.

When to Contact a Healthcare Professional

While mild tiredness is a possible side effect, extreme fatigue or fatigue accompanied by other symptoms can signal a more serious problem, such as kidney failure. Seek immediate medical attention if you experience:

Decreased urination or unusual back/side pain
Mental or mood changes, such as confusion or agitation
Easy bruising or bleeding
Yellowing of the skin or eyes (jaundice)

Valacyclovir vs. Acyclovir: Fatigue and Dosing Comparison

Valacyclovir and acyclovir are both antiviral medications used for herpes infections. Valacyclovir is a prodrug of acyclovir, offering higher bioavailability, which allows for less frequent dosing. This table compares their side effect profiles with a focus on fatigue.


Feature	Valacyclovir (Valtrex)	Acyclovir (Zovirax)
Mechanism	Converted to acyclovir in the body; inhibits viral DNA synthesis.	Inhibits viral DNA synthesis directly.
Common Side Effects	Headache, nausea, stomach pain, dizziness. Fatigue reported, particularly in HIV patients.	Nausea, headache, general ill feeling (malaise), diarrhea. Fatigue also reported.
Dosing Frequency	Less frequent due to higher bioavailability (e.g., twice daily).	More frequent (e.g., up to five times daily).
Associated Fatigue	Fatigue is a known, though not universal, side effect. More frequently noted in immunocompromised groups.	Fatigue is also a known potential side effect.

Conclusion

Yes, valacyclovir can cause tiredness, although it is not a universally experienced side effect. For most people, it is generally mild and manageable. However, certain individuals, such as those with compromised immune systems, kidney issues, or of advanced age, face a higher risk of experiencing fatigue or other adverse neurological effects. Staying well-hydrated, ensuring adequate rest, and being aware of other more serious symptoms are key management strategies. Always consult your healthcare provider if fatigue is severe or if you experience concerning symptoms, as a dose adjustment or different medication may be necessary. For more information on valacyclovir and other antivirals for HIV, you can visit the HIV.gov database on patient information.

Potential Drug Interactions

Before starting valacyclovir, it is crucial to inform your doctor about all other medications you are taking. Some medications, especially those affecting the kidneys, can interact with valacyclovir and increase the risk of side effects. This includes nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen. Your healthcare provider can screen for potential harmful interactions to ensure safe and effective treatment.

Frequently Asked Questions

Yes, fatigue is a known side effect of valacyclovir, though it's not experienced by everyone. Clinical studies found it was reported more frequently in some patient populations, such as those with HIV, compared to placebo.

The likelihood varies among individuals. While not a top-tier common side effect in the general population, data from HIV-1-infected subjects showed 8% reported fatigue, compared to 5% on placebo. Higher doses or underlying conditions like kidney problems may increase the risk.

For mild fatigue, ensure you are well-hydrated and getting adequate rest. If tiredness persists or is severe, speak with your healthcare provider. They can assess if the dosage needs adjustment or if other factors are contributing.

In most cases, fatigue is a mild side effect. However, extreme tiredness combined with other symptoms like decreased urination or confusion could indicate a more serious problem, such as kidney failure. If this occurs, seek immediate medical care.

The side effect profiles of valacyclovir and acyclovir are similar, as valacyclovir converts to acyclovir in the body. Both medications list fatigue or tiredness as a possible side effect. The difference often lies in dosing frequency, as valacyclovir allows for fewer doses per day.

Yes, higher doses of valacyclovir can increase the risk of side effects. If you have underlying kidney issues, the drug can accumulate, potentially increasing the risk of both mild fatigue and more serious neurological side effects.

Yes, drinking plenty of fluids is recommended while taking valacyclovir. Staying hydrated supports kidney function, which is crucial for processing the medication and can help prevent dehydration-related fatigue.