What are the long-term side effects of valacyclovir?

October 7, 2025 •

4 min read

While generally well-tolerated for long-term suppressive therapy, valacyclovir can, in rare instances, lead to serious chronic complications, primarily involving the kidneys and central nervous system, particularly in vulnerable populations. It is crucial to understand what are the long-term side effects of valacyclovir.

Quick Summary

Serious long-term side effects of valacyclovir are rare, but can include acute kidney failure, central nervous system toxicity, and blood disorders like TTP/HUS, primarily affecting patients with pre-existing conditions or high-dose regimens.

Key Points

Rare but serious side effects: Though generally safe for long-term use in healthy people, valacyclovir can rarely cause serious side effects, primarily affecting the kidneys and central nervous system.
Renal toxicity risk: Patients with pre-existing kidney disease, elderly individuals, and those who are dehydrated face a higher risk of acute kidney injury from valacyclovir.
Neurotoxicity concerns: Rare neurotoxicity can lead to confusion, hallucinations, and seizures, especially in older adults or those with renal impairment.
Special precautions for immunocompromised: Severely immunocompromised individuals, like transplant or advanced HIV patients, are at a rare risk for blood disorders (TTP/HUS) with high-dose, long-term therapy.
Importance of monitoring: Regular monitoring of kidney function is recommended for patients on chronic suppressive therapy, especially for those in high-risk groups.
Symptoms of concern: Key signs that warrant immediate medical attention include unusual fatigue, decreased urination, confusion, or swelling.

Valacyclovir is an antiviral medication prescribed to treat infections caused by herpes simplex virus (HSV), such as cold sores and genital herpes, and varicella-zoster virus (VZV), which causes shingles. It works by converting into acyclovir in the body, which inhibits viral DNA synthesis. Due to its improved bioavailability over acyclovir, valacyclovir can be taken less frequently, making it a convenient option for suppressive therapy. For many people, long-term use is effective and well-tolerated, with studies documenting its safety for chronic suppression for several years. However, it is essential for patients and healthcare providers to be aware of the rare, but potentially serious, long-term side effects, particularly for those with pre-existing health conditions.

Long-Term Safety Profile of Valacyclovir

For most healthy individuals, long-term suppressive therapy with valacyclovir is considered safe when taken as directed by a healthcare provider. Clinical trials and post-marketing surveillance have monitored the safety and have found the overall profile to be favorable. The Centers for Disease Control and Prevention (CDC) guidelines note that long-term therapy with antivirals like valacyclovir is effective and safe for many patients with frequent recurrences. For example, in studies involving thousands of immunocompetent and immunocompromised individuals receiving long-term valacyclovir for HSV suppression, the safety profiles were comparable to placebo or acyclovir. Still, it is not without risks, especially in certain patient populations.

Rare but Potentially Serious Side Effects

Though rare, certain serious adverse events have been reported with long-term valacyclovir use. These side effects primarily affect the kidneys and central nervous system and are more likely to occur in high-risk individuals.

Renal Toxicity (Kidney Problems)

Valacyclovir is primarily excreted by the kidneys. In rare cases, high doses, dehydration, or pre-existing kidney dysfunction can lead to a potentially serious condition known as acute kidney injury (AKI).

Mechanism: AKI from valacyclovir can result from the deposition of acyclovir crystals in the renal tubules, leading to obstruction and inflammation.
Risk Factors: Elderly patients, individuals with kidney disease, and those on other nephrotoxic medications are at increased risk. In some reported cases, AKI occurred even with normal dosing in patients without known renal issues.
Symptoms: Signs of kidney problems include decreased urine output, fatigue, confusion, and swelling in the ankles or feet.

Central Nervous System (CNS) Effects

Neurotoxicity is a rare but serious side effect that can occur with valacyclovir, especially in older adults or those with impaired renal function. The accumulation of the active metabolite, acyclovir, is believed to cross the blood-brain barrier and cause these effects.

Symptoms: Manifestations of CNS toxicity can include:
- Confusion and agitation
- Hallucinations (auditory or visual)
- Seizures or tremors
- Aggressive behavior
- Encephalopathy
Resolution: Most neurotoxic effects are reversible upon discontinuation of the medication, though full recovery time can vary.

Hematologic (Blood) Disorders

Severely immunocompromised patients, such as those with advanced HIV disease or bone marrow/kidney transplants, face a rare but life-threatening risk of developing thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) when taking high doses of valacyclovir. These conditions involve blood clots forming in small blood vessels and can lead to organ damage.

Liver Inflammation

Post-marketing reports have noted cases of liver problems, including increased liver enzymes and hepatitis, though these are rare and a direct causal link is not always confirmed. Symptoms of liver issues include jaundice (yellowing skin/eyes), abdominal pain, and nausea.

Comparison of Long-Term Valacyclovir and Acyclovir

For long-term suppressive therapy, valacyclovir offers dosing advantages over acyclovir due to its higher bioavailability. Both medications are generally safe and effective, but their profiles differ slightly.


Feature	Valacyclovir (Prodrug of Acyclovir)	Acyclovir
Bioavailability	Higher oral bioavailability, converted to acyclovir in the liver.	Lower oral bioavailability.
Dosing Frequency	Less frequent dosing (e.g., once or twice daily) for long-term suppression.	More frequent dosing (e.g., several times a day) required to maintain therapeutic levels.
Risk Factors for Serious Side Effects	Higher risk in patients with renal impairment, advanced age, and immunosuppression.	Higher risk in patients with renal impairment and immunosuppression, similar to valacyclovir.
Toxicity Profile	Generally well-tolerated; rare risks include renal toxicity, CNS effects, TTP/HUS.	Similar overall safety profile; rare risks include renal toxicity, CNS effects, TTP/HUS.

Managing Risks During Chronic Valacyclovir Therapy

To minimize the risk of developing long-term side effects, several precautions should be taken under medical supervision:

Renal Function Monitoring: Individuals on long-term therapy, particularly the elderly or those with kidney issues, should have their renal function regularly monitored via blood tests (e.g., serum creatinine).
Stay Hydrated: Adequate fluid intake is crucial to prevent crystal precipitation in the kidneys.
Dose Adjustment: Dosage may need to be adjusted in patients with renal impairment to prevent drug accumulation and toxicity.
Know the Symptoms: Patients should be aware of the signs of potential side effects, such as unusual fatigue, confusion, or reduced urination, and contact their doctor immediately if they appear.

Conclusion

While valacyclovir is an effective and generally safe medication for long-term suppressive therapy, particularly in immunocompetent individuals, awareness of its rare but serious long-term side effects is vital. The most significant risks involve renal toxicity and CNS effects, which are more common in older adults and those with compromised kidney function or immune systems. By ensuring proper dosing, monitoring, and patient awareness, healthcare providers can mitigate these risks and ensure the safe use of this important antiviral medication. Patients should always consult their doctor to discuss their individual risk profile and any concerns regarding chronic use. For detailed treatment guidelines, consult resources such as those provided by the Centers for Disease Control and Prevention (CDC).

Frequently Asked Questions

No, the serious long-term side effects of valacyclovir, such as kidney damage or neurological issues, are considered rare. Studies have shown that the medication is generally well-tolerated during long-term suppressive therapy in healthy individuals.

In rare instances, valacyclovir can cause acute kidney injury (AKI), particularly in high-risk groups like the elderly or those with pre-existing renal problems. While typically reversible upon stopping the medication and with proper management, a risk of longer-term complications exists, especially if left untreated.

Yes, for many healthy individuals, taking valacyclovir for long-term suppressive therapy is safe and effective under a doctor's supervision. The safety and efficacy for chronic use have been documented for up to 10 years for some indications.

Symptoms of a kidney problem, such as acute kidney injury, can include decreased urine output, fatigue, confusion, nausea, and swelling in the feet, hands, or ankles.

In rare cases, valacyclovir can cause central nervous system (CNS) effects, including confusion, agitation, hallucinations, and depression, especially in high-risk groups or at high doses. These effects are usually reversible upon discontinuation of the medication.

The risk for serious side effects, such as renal or CNS toxicity, is higher in specific populations, including elderly individuals, people with pre-existing kidney disease, and those who are severely immunocompromised.

If you experience any symptoms that suggest a serious side effect, such as confusion, hallucinations, or signs of kidney injury, you should contact your healthcare provider immediately. They can evaluate your condition and determine the appropriate course of action.

Yes, dehydration is a known risk factor that can increase the chances of valacyclovir-induced acute kidney injury. It is important to drink plenty of fluids while taking the medication, especially during long-term use.