Valacyclovir Use in Chronic Kidney Disease
Valacyclovir is not contraindicated in CKD but requires significant dose adjustment based on creatinine clearance to prevent neurotoxicity. 1
Dosing Recommendations Based on Renal Function
Valacyclovir is primarily eliminated by the kidneys, and its accumulation in patients with renal impairment can lead to serious neurological complications. The FDA-approved dosing recommendations for adults with reduced renal function are as follows:
For creatinine clearance 30-49 mL/min:
- For herpes zoster: 1 gram every 12 hours
- For genital herpes (recurrent): No reduction from standard dose
- For genital herpes (suppressive therapy): No reduction from standard dose
For creatinine clearance 10-29 mL/min:
- For herpes zoster: 1 gram every 24 hours
- For genital herpes (recurrent): 500 mg every 24 hours
- For genital herpes (suppressive therapy): 500 mg every 24 hours
For creatinine clearance <10 mL/min:
- For herpes zoster: 500 mg every 24 hours
- For genital herpes (recurrent): 500 mg every 24 hours
- For genital herpes (suppressive therapy): 500 mg every 24 hours 1
Special Considerations for Dialysis Patients
Hemodialysis
- Patients should receive the recommended dose after hemodialysis
- During hemodialysis, the half-life of acyclovir is approximately 4 hours
- About one-third of acyclovir is removed during a 4-hour hemodialysis session 1
Peritoneal Dialysis
- Supplemental doses are not required following CAPD or CAVHD
- The removal of acyclovir after CAPD and CAVHD is less pronounced than with hemodialysis
- Pharmacokinetic parameters closely resemble those observed in patients with ESRD not receiving hemodialysis 1
Risks of Improper Dosing in CKD
Failure to adjust valacyclovir dosing in patients with renal impairment can lead to valacyclovir-associated neurotoxicity (VAN), which manifests as:
- Confusion
- Altered level of consciousness
- Hallucinations
- Agitation
- Dysarthria 2
In patients with ESRD, the half-life of valacyclovir can be up to 14 hours, significantly increasing the risk of toxicity with standard dosing 3. Recent case reports document severe neurotoxicity requiring hospitalization and emergent hemodialysis in patients who received inappropriate doses 3, 2.
Mechanism of Neurotoxicity
The neurotoxicity is related to higher concentrations of acyclovir and its metabolites (particularly CMMG) in both the systemic circulation and cerebrospinal fluid. While renal impairment does not alter the propensity for acyclovir or its metabolites to distribute to the CSF, the higher concentrations in the systemic circulation due to reduced elimination lead to proportionally higher concentrations in CSF 4.
Management of Valacyclovir Toxicity
If neurotoxicity develops:
- Immediately discontinue valacyclovir
- Consider hemodialysis in severe cases to enhance drug clearance
- Monitor for clinical improvement, which typically occurs within 1-7 days after drug discontinuation in most patients 2
Conclusion
Valacyclovir can be used in patients with CKD, including those on dialysis, but appropriate dose adjustment is essential to prevent serious neurological complications. The risk of neurotoxicity is particularly high in elderly patients and those with advanced renal dysfunction. Healthcare providers should be vigilant about dosing adjustments and monitoring for early signs of neurotoxicity in this population.
In rare cases, valacyclovir has been associated with nephrotoxicity even in patients with previously normal renal function, highlighting the importance of monitoring renal function during treatment 5, 6.
Always consult the most current prescribing information and consider individual patient factors when determining appropriate dosing in CKD patients.