Side Effects of Valacyclovir Suppressive Therapy for HSV-2
Valacyclovir suppressive therapy for genital HSV-2 is generally well-tolerated in immunocompetent adults, with the most common side effects being headache (35-38%), nausea (11%), and abdominal pain (9-11%), which occur at rates only slightly higher than placebo. 1
Common Side Effects (>5% incidence)
The FDA-approved labeling from clinical trials of suppressive therapy in immunocompetent adults identifies the following adverse reactions 1:
- Headache occurs in 35-38% of patients on suppressive therapy (compared to 34% on placebo) 1
- Nausea affects 11% of patients (versus 8% on placebo) 1
- Abdominal pain occurs in 9-11% of patients (versus 6% on placebo) 1
- Dysmenorrhea in 5-8% of female patients (versus 4% on placebo) 1
- Depression reported in 5-7% (versus 5% on placebo) 1
- Arthralgia in 5-6% (versus 4% on placebo) 1
- Dizziness in 2-4% (versus 1% on placebo) 1
- Vomiting in 3% (versus 2% on placebo) 1
Laboratory Abnormalities
No routine laboratory monitoring is required for patients on suppressive therapy unless they have substantial renal impairment. 2 However, the following laboratory changes have been documented 1:
- Elevated liver enzymes (AST) in approximately 3-4% of patients 1
- Decreased white blood cell counts (<0.75 x lower limit of normal) in 0.7-0.8% 1
- Decreased platelet counts (<100,000/mm³) in 0.4-1.1% 1
- Anemia (hemoglobin <0.8 x lower limit of normal) in <1% 1
Serious Adverse Reactions (Rare at Suppressive Doses)
Critical Safety Distinction by Dose
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) has been reported in immunocompromised patients receiving high-dose valacyclovir (8 grams/day) but has NOT been reported at the doses used for HSV suppression (500 mg to 1 gram daily). 2, 1
- This serious complication is not a concern at standard suppressive doses in immunocompetent patients 2
- The risk appears limited to severely immunocompromised patients (particularly advanced HIV disease) receiving doses 8-16 times higher than standard suppressive therapy 2, 3
Other Rare Serious Effects
- Acute renal failure can occur, particularly with inadequate hydration, but is uncommon at suppressive doses 1
- Central nervous system effects (confusion, hallucinations, agitation) are rare and typically occur in patients with renal impairment or elderly patients 1
Long-Term Safety Profile
Valacyclovir has documented safety for up to 1 year of continuous suppressive therapy in immunocompetent patients, with no clinically significant development of viral resistance. 4, 5
- Resistance rates remain below 0.5% in immunocompetent patients despite 20+ years of widespread clinical use 4
- Safety has been documented for up to 6 years with acyclovir (the active metabolite) 2, 5
Comparative Tolerability
The side effect profile of valacyclovir at suppressive doses is comparable to placebo for most adverse events, with only headache, nausea, and abdominal pain occurring at modestly higher rates. 1, 6, 7
- In clinical trials, adverse events were comparable between valacyclovir and placebo arms 6
- The medication is generally well-tolerated with low discontinuation rates due to adverse effects 3, 6, 7
Common Pitfalls to Avoid
- Do not confuse the safety profile of high-dose valacyclovir (8 g/day for CMV prophylaxis) with standard suppressive doses (500 mg to 1 g/day for HSV-2) - the risk of TTP/HUS does not apply to standard suppressive therapy 2, 1
- Do not routinely order laboratory monitoring unless the patient has pre-existing renal impairment 2
- Ensure adequate hydration to minimize any potential nephrotoxicity risk, though this is minimal at suppressive doses 4