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

Valtrex (valacyclovir) is a well-tolerated antiviral medication with a strong safety record. For most patients, side effects are mild and temporary. But there are a few serious side effects that you need to know about — especially if you have kidney problems, are elderly, or are immunocompromised. Here's a complete breakdown.

Common Side Effects of Valtrex (Usually Mild)

The most frequently reported side effects of valacyclovir are generally mild and resolve on their own:

Headache — The most common side effect. Usually mild to moderate. Taking the medication with food and staying well hydrated can help.

Nausea — Relatively common, especially at higher doses. Taking valacyclovir with food can significantly reduce nausea.

Vomiting — Less common than nausea but possible, especially early in a course of treatment.

Diarrhea — May occur, typically mild. Stay hydrated.

Dizziness — Some patients report dizziness. Use caution when driving or operating machinery until you know how valacyclovir affects you.

Abdominal pain — Stomach discomfort is occasionally reported.

Fatigue — Feeling tired is possible, particularly during a course for shingles (though fatigue from shingles itself is also common).

These side effects are generally mild and manageable. Most resolve within a few days or after completing the course of treatment.

Serious Side Effects: When to Call Your Doctor Right Away

The following side effects are less common but potentially serious. Contact your healthcare provider or go to an emergency room immediately if you experience any of these:

Kidney problems. Valacyclovir is processed through the kidneys and can cause kidney damage in some patients. Warning signs: decreased urination, swelling in legs or feet, unusual tiredness, confusion. Risk is higher in patients who are dehydrated, elderly, or have pre-existing kidney disease.

Central nervous system (CNS) effects. Valacyclovir can rarely cause neuropsychiatric symptoms, particularly in elderly patients or those with kidney problems. Signs include: agitation, confusion, hallucinations, seizures, unsteady movements. If any of these occur, stop the medication and contact your doctor immediately.

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). This rare but life-threatening condition has been reported in immunocompromised patients (HIV, transplant recipients) at very high doses. Signs: fever, easy bruising or bleeding, red spots on skin (not herpes-related), bloody diarrhea, extreme weakness, yellowing of skin or eyes. This is a medical emergency — call 911.

Severe allergic reactions. Rare but possible. Signs: hives, difficulty breathing, swelling of the face, lips, tongue, or throat. Stop the medication and call 911 or go to the nearest emergency room immediately.

Who Is at Higher Risk for Side Effects?

Most people tolerate valacyclovir well. However, certain groups are at higher risk for serious side effects:

Patients with kidney disease or on dialysis: Dose adjustment is required. Your doctor must reduce the dose based on your kidney function (creatinine clearance).

Adults 65 and older: More likely to have age-related decline in kidney function, making them more susceptible to CNS and kidney side effects.

Immunocompromised patients: Higher doses may be used, and TTP/HUS risk is greater in this population.

Dehydrated patients: Adequate hydration is critical when taking valacyclovir. Drink at least 8 glasses of water daily while on treatment.

Tips to Minimize Side Effects

Take valacyclovir with food to reduce nausea and stomach upset

Drink plenty of water — at least 6–8 glasses per day while on treatment

Do not take NSAIDs (ibuprofen, naproxen) while on valacyclovir unless your doctor approves — both can strain the kidneys

Do not combine valacyclovir with acyclovir — they both act on the same pathway and combining doubles your exposure

Does Valtrex Have a Boxed Warning?

No. Valacyclovir does not carry an FDA black box warning. This is the highest level of drug safety warning that the FDA requires on certain medications. Valacyclovir's safety profile is generally considered favorable — serious adverse effects are rare and typically occur in patients with identifiable risk factors.

Bottom Line

Valtrex is safe for most patients. Headache and nausea are the most common side effects — take it with food and stay hydrated to reduce them. If you experience confusion, agitation, decreased urination, bruising, or difficulty breathing, contact your healthcare provider or emergency services immediately. Also see our guide on Valtrex drug interactions to make sure your other medications are safe to take at the same time.