From the Guidelines
High doses of valtrex (valacyclovir) in patients with end-stage renal disease (ESRD) can cause neurotoxicity, including encephalopathy, due to reduced kidney function leading to drug accumulation and high blood levels crossing the blood-brain barrier. The most recent and highest quality study, 1, provides guidelines for managing chronic kidney disease in patients infected with HIV, including dosage adjustments for various medications, but does not directly address valtrex dosage in ESRD. However, an earlier study, 1, provides specific dosage adjustments for valtrex in patients with renal insufficiency, recommending a dose of 500 mg every 24-48 hours for patients with creatinine clearance less than 30 mL/min. Key points to consider in managing valtrex in ESRD patients include:
- Proper dose adjustment based on creatinine clearance to prevent drug accumulation and neurotoxicity
- Administration of valtrex after dialysis sessions for patients on dialysis
- Immediate discontinuation of valtrex and provision of supportive care if encephalopathy symptoms develop
- Consideration of alternative antiviral medications with different clearance mechanisms if antiviral therapy is still necessary. It is essential to prioritize the patient's morbidity, mortality, and quality of life when managing valtrex in ESRD, and to carefully monitor for signs of neurotoxicity, such as confusion, hallucinations, agitation, tremors, and altered consciousness.
From the FDA Drug Label
Central nervous system adverse reactions, including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy, have been reported in both adult and pediatric patients with or without reduced renal function and in patients with underlying renal disease who received higher-than-recommended doses of VALTREX for their level of renal function
- Encephalopathy is a reported central nervous system adverse reaction associated with high doses of valtrex in patients with underlying renal disease, including those with end-stage renal disease (ESRD) 2.
- High doses of valtrex can cause central nervous system effects, including encephalopathy, in patients with ESRD, and the drug should be discontinued if these reactions occur.
- Dosage reduction is recommended when administering valtrex to patients with renal impairment to minimize the risk of adverse reactions.
From the Research
High Doses of Valtrex in ESRD and Encephalopathy
- High doses of valtrex (valacyclovir) in patients with end-stage renal disease (ESRD) can lead to neurotoxicity, including encephalopathy, as reported in several case studies 3, 4, 5, 6, 7.
- Valacyclovir is renally cleared and can accumulate in patients with renal dysfunction, leading to severe side effects due to the prolonged half-life 3.
- The administered dose of valacyclovir was higher than the recommended dose based on renal function in many cases, resulting in severe neurological and physical manifestations 3, 4, 5, 6.
- Symptoms of valacyclovir-associated neurotoxicity include confusion, altered level of consciousness, hallucinations, agitation, and dysarthria 5.
- Discontinuation of the antiviral and additional clearance by dialysis are the basis of treatment for valacyclovir-associated neurotoxicity 4, 5, 6, 7.
- Regular monitoring of renal function and consciousness is necessary during valacyclovir treatment, especially in the elderly, even if renal function is normal 7.
Risk Factors for Encephalopathy
- Advanced age and impaired renal function are risk factors for valacyclovir-associated neurotoxicity, including encephalopathy 5.
- High doses of valacyclovir, especially in patients with ESRD, can increase the risk of encephalopathy 3, 4, 6.
- Acute kidney injury can also occur after administration of valacyclovir, even in patients with normal renal function, and can contribute to the development of encephalopathy 7.
Treatment and Management
- Discontinuation of valacyclovir and initiation of hemodialysis can lead to rapid improvement of symptoms and recovery from valacyclovir-associated neurotoxicity, including encephalopathy 3, 4, 6, 7.
- Intensification of peritoneal dialysis can also be effective in treating valacyclovir-associated neurotoxicity 4.