What are the potential side effects of Valtrex (valacyclovir) in adults with a history of herpes simplex virus (HSV) or varicella-zoster virus (VZV) infections, particularly those with impaired renal function?

Valtrex Side Effects

Valtrex (valacyclovir) is generally well-tolerated with headache and nausea being the most common side effects, but serious adverse events including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), acute renal failure, and central nervous system toxicity can occur, particularly in patients with renal impairment or those receiving high doses. 1

Common Side Effects (Generally Well-Tolerated)

Most Frequent Adverse Events:

• Headache is the most commonly reported side effect across all indications 2, 3, 4
• Nausea occurs frequently, particularly at higher doses 1, 3, 4
• Gastrointestinal disturbances including abdominal pain, vomiting, and diarrhea are reported, especially with high-dose therapy (8g/day) 2

These common side effects typically do not require discontinuation of therapy and occur at similar rates to acyclovir or placebo 3, 4

Serious Adverse Events Requiring Immediate Attention

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

Critical Warning: TTP/HUS, sometimes resulting in death, has been reported in specific high-risk populations 1:

• Patients with advanced HIV-1 disease receiving high-dose valacyclovir (8g/day) 1, 2
• Allogeneic bone marrow transplant recipients on 8g/day dosing 1
• Renal transplant recipients participating in clinical trials at 8g/day 1

Management: Treatment with valacyclovir must be stopped immediately if clinical signs, symptoms, and laboratory abnormalities consistent with TTP/HUS occur 1

Important Caveat: This serious complication is primarily associated with very high doses (8g/day) used for CMV prophylaxis, not standard doses used for HSV or VZV treatment 2

Acute Renal Failure

High-Risk Populations for Renal Toxicity: 1

• Elderly patients with or without pre-existing reduced renal function 1
• Patients with underlying renal disease who received higher-than-recommended doses for their level of renal function 1
• Patients receiving other nephrotoxic drugs concurrently 1
• Patients without adequate hydration - precipitation of acyclovir in renal tubules may occur when solubility (2.5 mg/mL) is exceeded 1

Prevention Strategy:

• Dose adjustment is mandatory for patients with renal impairment (CrCl <50 mL/min) 1
• Maintain adequate hydration for all patients 1
• Exercise caution when co-administering with nephrotoxic drugs 1
• In acute renal failure with anuria, hemodialysis may be beneficial until renal function is restored 1

Central Nervous System (CNS) Adverse Reactions

Neuropsychiatric Side Effects Include: 1, 5

• Agitation, hallucinations, confusion, and delirium 1
• Seizures and encephalopathy 1
• Psychosis (rare but documented even in patients with normal renal function) 5

Populations at Highest Risk:

• Elderly patients are more likely to experience CNS adverse reactions 1
• Patients with renal impairment - valacyclovir's pharmacokinetics are significantly altered with reduced clearance and prolonged half-life, increasing risk of drug accumulation and neurological complications 5
• Patients receiving higher-than-recommended doses for their level of renal function 1

Management: Valacyclovir should be discontinued immediately if CNS adverse reactions occur 1

Special Considerations for Renal Impairment

Dose Adjustments Required: 1

For patients with CrCl 30-49 mL/min:

• Herpes zoster: 1 gram every 12 hours (vs. every 8 hours in normal function) 1
• Genital herpes treatment: No reduction needed 1
• Suppressive therapy: No reduction needed 1

For patients with CrCl 10-29 mL/min:

• Herpes zoster: 1 gram every 24 hours 1
• Genital herpes: 500 mg every 24 hours 1

For patients with CrCl <10 mL/min:

• Herpes zoster: 500 mg every 24 hours 1
• Genital herpes: 500 mg every 24 hours 1

Hemodialysis patients should receive the recommended dose after hemodialysis, as approximately one-third of acyclovir is removed during a 4-hour session 1

Critical Pitfalls to Avoid

Do not use 8g daily doses in patients with advanced HIV disease or severe immunocompromise due to TTP/HUS risk 1, 2

Always verify renal function before prescribing any valacyclovir dose, as renal impairment significantly increases risk of all adverse effects 1, 5

Ensure adequate hydration to minimize crystalluria and nephrotoxicity risk 1

Monitor elderly patients closely as they are at higher risk for both renal and CNS adverse effects 1

Discontinue immediately if signs of TTP/HUS (thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction) or CNS toxicity develop 1