What are the common and severe side effects of suppressive valacyclovir (valacyclovir) in an adult patient with a history of recurrent herpes simplex virus infections?

Side Effects of Suppressive Valacyclovir

Suppressive valacyclovir is generally well tolerated with minimal adverse events, with headache being the most common side effect occurring in approximately 35-38% of patients, followed by nausea (11%) and abdominal pain (11%). 1

Common Side Effects (>10% incidence)

The FDA-approved labeling identifies the following common adverse reactions in suppressive therapy trials:

• Headache occurs in 35-38% of patients on suppressive therapy, though this is similar to placebo rates (34%) 1
• Nausea affects approximately 11% of patients, compared to 8% on placebo 1
• Abdominal pain occurs in 11% of patients versus 6% on placebo 1

Less Common Side Effects (5-10% incidence)

• Dysmenorrhea (8% vs 4% placebo) 1
• Depression (7% vs 5% placebo) 1
• Arthralgia (6% vs 5% placebo) 1
• Dizziness (4% vs 1% placebo) 1
• Vomiting (3% vs 2% placebo) 1

In HIV-infected patients on suppressive therapy, additional commonly reported reactions include:

• Fatigue (8% vs 5% placebo) 1
• Rash (8% vs 1% placebo) 1

Serious but Rare Adverse Events

Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndrome (TTP/HUS)

• This potentially fatal complication has been reported in immunocompromised patients receiving high-dose valacyclovir (8g/day) for CMV prophylaxis, but has NOT been reported at standard doses used for HSV suppression (500mg-1g daily) 2, 3, 4
• The risk appears highest in patients with advanced HIV disease 4
• At standard suppressive doses for genital herpes, this complication is not a concern 2

Acute Renal Failure

• Adequate hydration should be maintained to minimize nephrotoxicity risk 2
• No routine laboratory monitoring is needed unless substantial renal impairment exists at baseline 2, 3
• Dose adjustment is not required for creatinine clearance ≥30 mL/min 2

Central Nervous System Effects

• Serious CNS effects are rare but can occur, particularly in patients with renal impairment 1

Laboratory Abnormalities

In suppressive therapy trials, the following laboratory changes were observed:

• Elevated ALT (3.8% vs 4.1% placebo) 1
• Decreased platelet counts (1.1% vs 1.5% placebo) 1
• Decreased white blood cells (0.8% vs 1.5% placebo) 1
• Decreased hemoglobin (0.8% vs 0.8% placebo) 1

These laboratory abnormalities occurred at similar or lower rates compared to placebo, indicating they are not clinically significant concerns 1

Long-Term Safety Data

• Safety and efficacy have been documented for up to 6 years with acyclovir and 1 year with valacyclovir 2
• Long-term studies show that serious complications such as hepatitis B infections, leukopenia, and severe headaches occur at very low rates (0.2%) 5
• Resistance development remains below 0.5% in immunocompetent patients despite 20+ years of widespread use 2

Clinical Context

The side effect profile of suppressive valacyclovir is remarkably benign, with most adverse events occurring at rates similar to placebo. The most common side effects (headache, nausea, abdominal pain) are generally mild and self-limited 6, 1. Studies specifically evaluating long-term suppressive therapy found that adverse events were comparable between valacyclovir and placebo groups, with no increase in serious adverse events 6, 5, 7, 8.

Important caveat: The serious adverse events (TTP/HUS, acute renal failure) that have been reported with valacyclovir occurred almost exclusively in immunocompromised patients receiving high doses (8g/day) for CMV prophylaxis, not at the standard suppressive doses (500mg-1g daily) used for genital herpes 2, 3, 4.