Nephrol Dial Transplant (2003) 18: 2680
© 2003 European Renal Association-European Dialysis and Transplant Association
Letter and Reply
Aciclovir and valaciclovir neurotoxicity in patients with renal failure
Renal Unit Southend Hospital Westcliff-on-Sea, UK Email: dralmond{at}cannonbury.demon.co.uk
Sir,
Helldén et al. [1] describe serious neurological adverse side effects during aciclovir (ACV) or valaciclovir (VACV) therapy in patients with renal failure and concluded that the determination of 9-carboxymethoxymethylguanine (CMMG) levels in serum may be a useful tool in supporting the diagnosis of ACV-associated neuropsychiatric symptoms. They went on to suggest pharmacokinetic studies were required to provide recommendations for dosing with ACV and VACV in renal failure.
Pharmacokinetic studies have been performed with ACV in oliguric patients on haemodialysis [2] and continuous ambulatory peritoneal dialysis (CAPD) [3], and have been performed with VACV on patients on CAPD [4]. Recommendations in dose adjustment taking into account the degree of renal failure and the mode of dialysis have been made. The common conclusion from these studies is that the recommended dose reduction provided by the manufacturers is inadequate for patients in end-stage renal failure requiring dialysis and does not take into account drug removal on haemodialysis.
The dose reduction required may be more significant in oliguric patients than in those with non-oliguric renal failure given that the normal route of excretion (91%) is via urine. Helldén et al. do not include an estimation of urine volumes in their patients which may have confounded some of their data as simple extrapolation of ACV clearance according to creatinine clearance may not be valid.
Prevention of neurotoxicity by dose reduction and the ability of haemodialysis, by rapid drug removal, to help differentiate between symptoms of encephalitis and ACV toxicity [5], whilst simultaneously proving therapeutic is possibly a better strategy to adopt than measurement of CMMG, which may subsequently serve to act as a confirmatory test.
Conflict of interest statement. None declared.
References
- Helldén A, Odar-Cederlöf I, Diener P et al. High serum concentrations of the acyclovir main metabolite 9-carboxymethoxymethylguanine in renal failure patients with acyclovir-related neuropsychiatric side effects: an observational study. Nephrol Dial Transplant 2003; 18: 1135–1141
[Abstract/Free Full Text] - Almond MK, Fan S, Dhillon S, Pollock AM, Raftery MJ. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron 1995; 69: 428–432[Medline]
- Stathoulopoulou F, Almond MK, Dhillon S, Raftery MJ. Clinical pharmacokinetics of oral acyclovir in patients on continuous ambulatory peritoneal dialysis. Nephron 1996; 74: 337–341[Medline]
- Stathoulopoulou F, Dhillon S, Thodis H, Stathakis C, Vargemezis V. Evaluation of valaciclovir dosage reduction in continuous ambulatory peritoneal dialysis patients. Nephron 2002; 91: 164–166[Medline]
- Beales P, Almond MK, Kwan JT. Acyclovir neurotoxicity following oral therapy: prevention and treatment in patients on haemodialysis. Nephron 1994; 66: 362–363[Medline]
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