[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?].
BACKGROUND
We report three cases of neurotoxicity in patients with renal failure, treated with Zelitrex (valacyclovir).


METHODS
The patients are two women and a man, aged 76 +/- 4.6 years, who presented acute mental confusion during a treatment with valacyclovir. In two cases, the patients previously had altered renal function and were under peritoneal dialysis. In the last case, the patient had simultaneous neurotoxicity and acute renal failure. After the discontinuation of the drug, the outcome was favourable in all cases.


CONCLUSIONS
Our cases focus attention on the possible neurotoxicity of valacyclovir, which is an amino acid ester prodrug of acyclovir, rapidly and almost completely hydrolysed to acyclovir prior to systemic exposure. The bioavailability of valacyclovir is 54% compared to approximately 20% for oral acyclovir and may account for unexpected overdoses, which may lead to serious neurological toxicity.
Centre régional de pharmacovigilance, hôpital Saint-Charles, CHU, 300, rue Auguste-Broussonnet, 34295 Montpellier, France. je;eme[euroere@voila.fr
H
H
Peyrière
B
B
Branger
C
C
Bengler
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F
Vécina
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V
Pinzani
D
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Hillaire-Buys
J P
JP
Blayac
D000212:Acyclovir / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000368:Aged; D000369:Aged, 80 and over; D001682:Biological Availability; D062787:Drug Overdose; D005260:Female; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced*; D011355:Prodrugs / Q000009:adverse effects* / Q000493:pharmacokinetics; D051437:Renal Insufficiency / Q000188:drug therapy; D000077483:Valacyclovir; D014633:Valine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
D011355:Prodrugs; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir