Valacyclovir neurotoxicity in a patient with end-stage renal disease treated with continuous ambulatory peritoneal dialysis

Okada, Toshiki; Nakao, Toshiyuki; Matsumoto, Hiroshi; Nagaoka, Yume; Iwasawa, Hideaki; Nanri, Kazuhide; Yamazaki, Takuya

doi:10.5414/cnp58168

Cited by 16 publications

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“…Perhaps, because VACV is more rapidly absorbed, VAN may develop unexpectedly, especially in elderly patients and those with renal failure. Linssen-Schuurmans et al [3] first reported VAN in 1998, and they and others have reported 20 cases since then [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17] (Table 1). ACV neurotoxicity usually appears within the first 24 to 72 h of treatment, with renal failure and neurotoxicity, and complete recovery usually follows within 2 to 7 days after treatment is discontinued [18].…”

Section: Discussionmentioning

confidence: 99%

Valacyclovir neurotoxicity: clinical experience and review of the literature

Asahi

Tsutsui

Wakasugi

et al. 2009

Euro J of Neurology

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Valacyclovir (VACV) is used increasingly to treat herpes zoster, although neuropsychiatric symptoms [VACV neurotoxicity (VAN) or acyclovir neurotoxicity], may accompany use of this drug. To promote awareness of this rare condition, we describe here two clinical cases of VAN we previously reported and review 20 cases from the literature. In all cases, chronic or acute renal failure preceded VAN. The symptoms of VAN varied, but disturbances of consciousness and hallucination occurred most commonly. When acute renal failure was due to the drug, recovery from both the disturbance of consciousness and renal failure followed within several days after discontinuation of VACV. Early recognition and diagnosis will ensure effective treatment of VAN.

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Section: Discussionmentioning

confidence: 99%

Valacyclovir neurotoxicity: clinical experience and review of the literature

Asahi

Tsutsui

Wakasugi

et al. 2009

Euro J of Neurology

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“…Acyclovir crosses the blood-brain barrier, a desirable quality for the treatment of herpes encephalitis, neonatal herpes simplex virus infections, and, possibly, multiple sclerosis (7,28). Acute, reversible neuropsychiatric symptoms were first associated with acyclovir therapy in the early 1980s (26), and similar adverse effects have been reported for the use of valacyclovir (1,2,10,12,15,21,24). Symptoms include ataxia, involuntary movements, dysarthria, disturbed consciousness, hyperreflexia, and deranged cerebral functions (hallucinations, confusion, and lethargy).…”

mentioning

confidence: 81%

Pharmacokinetics of Acyclovir and Its Metabolites in Cerebrospinal Fluid and Systemic Circulation after Administration of High-Dose Valacyclovir in Subjects with Normal and Impaired Renal Function

Smith¹,

Weller

Johnson³

et al. 2010

Antimicrob Agents Chemother

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Valacyclovir, the L-valyl ester prodrug of acyclovir (ACV), is widely prescribed to treat infections caused by varicella-zoster virus or herpes simplex virus. Rarely, treatment is complicated by reversible neuropsychiatric symptoms. By mechanisms not fully understood, this occurs more frequently in the setting of renal impairment. We characterized the steady-state pharmacokinetics of ACV and its metabolites 9-[(carboxymethoxy)methyl]-guanine (CMMG) and 8-hydroxy-acyclovir (8-OH-ACV) in cerebrospinal fluid (CSF) and the systemic circulation. We administered multiple doses of high-dose valacyclovir to 6 subjects with normal renal function and 3 subjects with chronic renal impairment (creatinine clearance [CrCl], ϳ15 to 30 ml/min). Dosages were 2,000 mg every 6 h and 1,500 mg every 12 h, respectively. Indwelling intrathecal catheters allowed serial CSF sampling throughout the dosing interval. The average steady-state concentrations of acyclovir, CMMG, and 8-OH-ACV were greater in both the systemic circulation and the CSF among subjects with impaired renal function than among subjects with normal renal function. However, the CSF penetration of each analyte, reflected by the CSF-to-plasma area under the concentration-time curve over the 6-or 12-h dosing interval (AUC ) ratio, did not differ based on renal function. Renal impairment does not alter the propensity for ACV or its metabolites to distribute to the CSF, but the higher concentrations in the systemic circulation, as a result of reduced elimination, are associated with proportionally higher concentrations in CSF.Valacyclovir, the L-valyl ester of the antiviral drug acyclovir (ACV), is widely prescribed for varicella-zoster virus and herpes simplex virus infections. Following oral administration, valacyclovir is rapidly and nearly completely hydrolyzed to acyclovir by first-pass intestinal and hepatic metabolism (13,27). Acyclovir crosses the blood-brain barrier, a desirable quality for the treatment of herpes encephalitis, neonatal herpes simplex virus infections, and, possibly, multiple sclerosis (7, 28). Acute, reversible neuropsychiatric symptoms were first associated with acyclovir therapy in the early 1980s (26), and similar adverse effects have been reported for the use of valacyclovir (1, 2, 10, 12, 15, 21, 24). Symptoms include ataxia, involuntary movements, dysarthria, disturbed consciousness, hyperreflexia, and deranged cerebral functions (hallucinations, confusion, and lethargy). Neuropsychiatric symptoms with valacyclovir are infrequent, but the risk increases with acute or chronic renal dysfunction, concomitant neurotoxic drugs, and advanced age (5, 11). The underlying mechanism for these side effects is unknown, and attempts to relate central nervous system (CNS) symptoms and systemic concentrations of acyclovir have been inconsistent (3,5,6,9), suggesting that a metabolite of acyclovir may be responsible or contributory (11).The major route of acyclovir elimination is the renal excretion of unchanged drug. Urinary recovery data after acyclovir a...

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“…1 The neurotoxicity of valacyclovir in patients undergoing CAPD has been documented at least in five reports. [2][3][4][5][6] In most cases, as in our patient, valacyclovir has been administered in a dosage above the recommended. However, valacyclovir neurotoxicity has occurred even when treatment was with adjusted dosage.…”

Section: Discussionmentioning

confidence: 99%

“…However, valacyclovir neurotoxicity has occurred even when treatment was with adjusted dosage. The recommended dosage for patients on CAPD is 500 mg every 24 h, although two pharmacokinetic studies suggested the same dosage every 48 h. 3,4 In patients with normal renal function, valacyclovir is excreted primarily as acyclovir (89%) in urine, after 2.5-3.3 h. In patients on CAPD (4 Â 2 L exchanges), the halftime elimination of the drug is prolonged to 14-20 h, while only 5.27 mL/min (0.355 L/h/1.73 m 2 ) are removed by the peritoneum (1% drug reduction during a 24 h collection period). 4,5 That low acyclovir clearance makes physicians to put patients receiving CAPD on conventional HD in case of valacyclovir neurotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…Usually, the neurotoxicity occurs with serum acyclovir levels >15 μmol/L, 4 although lower levels have also been reported. 3 Nephrologists should remain aware about valacyclovir neurotoxicity on CAPD patients and this intensification of CAPD can lead to its amelioration. For severe neurotoxicity symptoms, HD offers the fastest and the most efficient removal of acyclovir and should be used over PD.…”

Section: Discussionmentioning

confidence: 99%

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Intensification of Peritoneal Dialysis Improves Valacyclovir Neurotoxicity

et al. 2012

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Valacyclovir induced neurotoxicity is a life-threatening complication, usually starting 24-48 h after drug-peak serum concentrations. The elderly with impaired renal function seem to be the most susceptible group to valacyclovir neurotoxicity. Although hemodialysis is considered the best method for rapid drug removal, our case showed that intensive peritoneal dialysis regimen leads to the recovery of neurotoxicity after 3 days.

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Valacyclovir neurotoxicity in a patient with end-stage renal disease treated with continuous ambulatory peritoneal dialysis

Cited by 16 publications

References 0 publications

Valacyclovir neurotoxicity: clinical experience and review of the literature

Valacyclovir neurotoxicity: clinical experience and review of the literature

Pharmacokinetics of Acyclovir and Its Metabolites in Cerebrospinal Fluid and Systemic Circulation after Administration of High-Dose Valacyclovir in Subjects with Normal and Impaired Renal Function

Intensification of Peritoneal Dialysis Improves Valacyclovir Neurotoxicity

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