Common Side Effects of Valtrex (Valacyclovir)
The most common side effects of Valtrex are headache, nausea, and abdominal pain, occurring in more than 10% of patients, with these reactions generally mild and well-tolerated. 1
Most Frequent Adverse Reactions
Based on FDA labeling data from clinical trials, the following side effects occur most commonly:
Primary Side Effects (>10% incidence):
- Headache - reported in 13-35% of patients depending on indication and dosing regimen 1
- Nausea - occurs in 5-15% of patients 1
- Abdominal pain - seen in 3-11% of patients 1
Secondary Side Effects (2-10% incidence):
- Dizziness - reported in 2-4% of patients 1
- Vomiting - occurs in 3-6% of patients 1
- Fatigue - particularly in HIV-infected patients (8%) 1
- Rash - especially in HIV-infected patients (8%) 1
- Dysmenorrhea - in 5-8% of women on suppressive therapy 1
Gastrointestinal and Neurological Tolerability
The CDC guidelines confirm that valacyclovir is occasionally associated with nausea or headache, with these symptoms being the primary tolerability concerns in routine clinical practice 2. These side effects are typically mild and do not require treatment discontinuation in the vast majority of patients.
Laboratory Abnormalities
While generally not clinically significant, the following laboratory changes may occur:
- Mild ALT elevations (>2x upper limit of normal) in approximately 1.8% of patients 1
- AST elevations in 1-4% depending on indication 1
- Hemoglobin decreases - primarily when combined with ribavirin (not standard Valtrex monotherapy) 2
No routine laboratory monitoring is needed for patients on episodic or suppressive therapy unless substantial renal impairment exists 2.
Special Population Considerations
Immunocompromised Patients:
At standard doses for genital herpes treatment, valacyclovir maintains its favorable safety profile 3. However, high-dose valacyclovir (8 grams/day) has been associated with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in HIV-infected patients, though this has not been reported at standard therapeutic doses 2, 1.
Renal Impairment:
Patients with kidney disease require dose adjustment to prevent accumulation and potential neurotoxicity 3. The CDC recommends monitoring renal function and adjusting doses accordingly in patients with substantial renal impairment 2.
Rare but Serious Adverse Effects
While uncommon, clinicians should be aware of:
- Neurotoxicity - confusion, hallucinations, agitation (primarily in elderly patients with renal dysfunction) 4
- Acute kidney injury - crystal-induced nephropathy in susceptible patients 5
- Photosensitivity and rash - more common with simeprevir but can occur with valacyclovir 1
Clinical Implications
Treatment discontinuation due to adverse events occurs in only 1-2% of patients, demonstrating excellent overall tolerability 1. The side effect profile is comparable to placebo for most symptoms, with headache being the primary differentiating factor 1.
For patients experiencing mild headache or nausea, symptomatic treatment is usually sufficient without requiring discontinuation of valacyclovir therapy 3.