Valacyclovir Side Effects: What to Expect and When to Call Your Doctor

Valacyclovir (brand name Valtrex) is generally well-tolerated, especially at the doses used for most outpatient conditions. The most common side effects are mild and often resolve on their own. However, there are some important serious side effects — particularly related to kidney function and the central nervous system — that every patient should know about.

This guide covers everything you need to know about Valacyclovir side effects, from the very common to the rare-but-serious.

Common Side Effects of Valacyclovir

The most common side effects reported in clinical trials affect more than 10% of patients taking Valacyclovir. These are generally mild and often resolve on their own after a few days:

Headache: The most commonly reported side effect. Usually mild and manageable with hydration or OTC pain relievers (though discuss with your doctor first).

Nausea: Taking Valacyclovir with food can reduce nausea. The good news is that Valacyclovir can be taken with or without food.

Abdominal pain: Mild stomach discomfort that typically resolves as your body adjusts.

Fatigue: Mild fatigue or tiredness, reported in some patients especially at higher doses.

Rash: Mild skin rash is occasionally reported. Note: A severe rash with mucosal involvement is a serious symptom requiring immediate medical attention (see below).

Note: Valacyclovir does not cause drowsiness, so it will not impair your driving or ability to operate machinery.

Serious Side Effects: Call Your Doctor Right Away

While uncommon, the following side effects require prompt medical attention. Contact your healthcare provider immediately or go to an emergency room if you experience these:

Signs of kidney problems: Decreased or no urination, swelling in the legs or ankles, unusual weakness, difficulty breathing. Valacyclovir is cleared by the kidneys, and at high doses or in patients with pre-existing kidney disease, it can cause acute renal failure. Always stay well hydrated while taking Valacyclovir.

Central nervous system (CNS) effects: Agitation, confusion, hallucinations, unsteady movements, or difficulty speaking. These effects are more common in elderly patients or those with kidney impairment receiving higher-than-appropriate doses. Symptoms typically resolve when the medication is stopped.

Signs of a serious allergic reaction: Hives, difficulty breathing, swelling of face, lips, tongue, or throat. Seek emergency care immediately (call 911).

Severe skin reactions: Rare but serious skin reactions including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported. Stop Valacyclovir immediately if you develop a painful progressive rash with mucosal (mouth, eyes, genital) involvement, and seek emergency care.

TTP/HUS (blood disorder): Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported primarily in patients with advanced HIV disease or organ transplant recipients receiving very high doses (8g/day). At standard therapeutic doses in otherwise healthy patients, this risk is extremely rare. Signs include fever, easy bruising or bleeding, red spots on skin, pale or yellowed skin, weakness.

Who Is at Higher Risk for Side Effects?

Most patients tolerate Valacyclovir very well. However, certain groups face higher risk:

Elderly patients: Age-related decline in kidney function means elderly patients are at higher risk for both kidney damage and CNS side effects if doses are not appropriately adjusted.

Patients with kidney disease: Reduced renal clearance leads to higher drug levels. Dose adjustments are required for any patient with CrCl < 50 mL/min.

Dehydrated patients: Inadequate hydration reduces the kidney's ability to clear the drug. Drink plenty of fluids while taking Valacyclovir.

Immunocompromised patients: Patients with advanced HIV or those who have received bone marrow or organ transplants are at higher risk for rare serious adverse events.

Valacyclovir and Alcohol

There are no known clinically significant interactions between Valacyclovir and alcohol. However, alcohol can worsen some of Valacyclovir's side effects (nausea, dizziness, headache) and can dehydrate you, which is a concern since proper hydration is important while taking Valacyclovir. Moderate alcohol consumption is generally considered acceptable, but excessive drinking should be avoided.

Valacyclovir During Pregnancy and Breastfeeding

Decades of clinical data with Valacyclovir and acyclovir in pregnant women have not identified a drug-associated risk of major birth defects. The CDC and ACOG generally support the use of Valacyclovir suppressive therapy in pregnant patients with genital herpes during the third trimester to reduce the risk of neonatal transmission.

Valacyclovir can pass into breast milk. The decision to breastfeed while taking it should be made in consultation with your healthcare provider, weighing potential benefits and risks.

Simple Tips to Minimize Side Effects

Drink plenty of water throughout the day while taking Valacyclovir

Take it with food if you experience nausea

Tell your doctor about all other medications you take, especially any that can affect kidney function

Take the full prescribed course — don't stop early even if symptoms improve

The Bottom Line

Most patients taking Valacyclovir experience only mild, manageable side effects if any. Serious side effects are uncommon but important to recognize. Stay hydrated, take it as prescribed, and don't hesitate to call your doctor if you notice any concerning symptoms. For more information on what drugs to avoid while taking Valacyclovir, see our Valacyclovir Drug Interactions guide.