Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia

Murakami, Takuya; Akimoto, Tetsu; Okada, Mari; Hishida, Erika; Sugase, Taro; Miki, Atsushi; Kohara, Marina; Yoshizawa, Hiromichi; Masuda, Tomoyuki; Kobayashi, Takahisa; Saito, Osamu; Muto, Shigeaki; Nagata, Daisuke

doi:10.1177/1177392818782899

Cited by 8 publications

(12 citation statements)

References 38 publications

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“…Krieble et al described a case of combined acyclovir-induced nephrotoxicity and neurotoxicity in a newly diagnosed acquired immunodeficiency syndrome patient while receiving a high dose of intravenous acyclovir for disseminated herpes zoster infection [ 6 ]. Murakami et al described another case of combined valacyclovir-induced nephrotoxicity and neurotoxicity in an elderly woman [ 7 ]. In our patient, even though he had normal kidney function and received the appropriate dosage of oral valacyclovir for herpes zoster meningitis, he developed both nephrotoxicity and neuropsychiatric adverse events at the same time.…”

Section: Discussionmentioning

confidence: 99%

Concurrent Nephrotoxicity and Neurotoxicity Induced by Oral Valacyclovir in a Patient With Previously Normal Kidney Function

Abuhelwa¹,

Beran²,

Venkataramany³

et al. 2022

Cureus

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Drug-induced nephrotoxicity and neurotoxicity are commonly encountered problems in clinical practice. We describe a case of concurrent valacyclovir-induced nephrotoxicity and neurotoxicity in a 64-year-old man with no history of renal disease who developed acute renal injury and neurological symptoms after he received two weeks of the standard dose of oral valacyclovir for herpes zoster meningitis. His clinical condition improved significantly after the initiation of hemodialysis. Although nephrotoxicity due to intravenous infusion of valacyclovir and/or acyclovir is not uncommon, oral valacyclovir therapy is rarely associated with nephrotoxicity in patients with no history of renal insufficiency. Additionally, concurrent nephrotoxicity and neurotoxicity due to valacyclovir and/or acyclovir are rarely reported. Clinicians should be aware of these adverse events as immediate recognition and intervention are necessary to prevent morbidity.

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Section: Discussionmentioning

confidence: 99%

Concurrent Nephrotoxicity and Neurotoxicity Induced by Oral Valacyclovir in a Patient With Previously Normal Kidney Function

Abuhelwa¹,

Beran²,

Venkataramany³

et al. 2022

Cureus

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“…Ninety‐seven of those were included in the analysis, representing a total of 119 independent patients (Figure 1). The cases were extracted from 86 clinical cases 9‐35,37‐48,50‐54,56‐63,65‐71,73,75‐77,80‐83,85‐100,102,103 and 11 case series 36,49,55,64,72,74,78,79,84,101,113 . Figure 1 shows the case selection flow diagram.…”

Section: Resultsmentioning

confidence: 99%

“…Detection of acyclovir levels in plasma was requested in 53 cases (44.5%), with a mean of 17.2 mcg/ml ±25.3, and levels in CSF in 10 cases, 15,17,18,26,31,113 with a mean of 1.2 mcg/ml ±1.6. The CMMG metabolite was also obtained in 10 cases, 25,31,34,37,51,113 with 8 determinations in plasma, 8 in CSF and 1 in urine.…”

Section: Resultsmentioning

confidence: 99%

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Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases

et al. 2021

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What is known and objective Acyclovir and valacyclovir are commonly used antivirals with good general tolerance. Despite their good safety profile, they can cause systemic adverse effects, such as neurotoxicity, which are less frequent and known. The objective of this review was to collect all the reported cases of neurotoxicity associated with acyclovir and valaciclovir published in the literature and characterize their clinical course and interventions. Methods A systematic review of cases was carried out following the guidelines established by “Preferred Reporting Items for Systematic Reviews and Meta‐Analyses” (PRISMA). The research was carried out using the PubMed‐Medline and Embase databases, between July 1984 and March 2021. Results and discussion A total of 119 cases with neurotoxicity mainly related to acyclovir (n = 88; 73.9%), followed by valaciclovir (n = 35; 29.4%) were analysed. 49.6% (n = 59) were men with a mean age of 59.5 years ± 21.1 (0.5–88). In 83.3% of the cases, renal impairment was documented and 57.1% (n = 68) with end‐stage renal disease. The administered dose was higher than the renal adjustment recommendations in 59.7% of the cases. The global mean of onset of symptoms was 3.1 days ± 4.3 (0.2–28) after the start of antivirals. The mean recovery time was 9.8 days ± 21.7 (0.2–180). 74.4% of the patients had a recovery of ≤7 days, 15.9% between 8 and 15 days and 9.8% > 15 days. What is new and conclusion The neurotoxicity induced by acyclovir and its derivative valacyclovir is a poorly known and rare adverse effect that can occur mainly in patients with advanced age and impaired renal function. The most characteristic symptoms are confusion, altered level of consciousness, hallucinations, agitation and dysarthria. The basis of treatment is the discontinuation of the antiviral, and in some cases, it may require additional clearance by dialysis.

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“…In other case reports, oliguric renal failure could occur, and some required more complicated management such as hemodialysis or hemoperfusion. [23][24][25] Valacyclovir nephrotoxicity could present along with neurotoxicity, some with electrolyte imbalance, but neurotoxicity could present alone with a reserved renal function. 25,26…”

Section: Discussionmentioning

confidence: 99%

Valacyclovir Non-Oliguric Acute Kidney Injury: a Case Report of 84 Year-Old Female

Roongtanapirom¹

2020

bkkmedj

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alacyclovir is the L-valyl ester of the antiviral drug acyclovir, first studied in 1983 along with other acyclovir amino acid esters, searching for prodrugs to improve bioavailability and to decrease the toxicity of acyclovir.1 Valacyclovir is chemically stable in aqueous solution and 54% is absorbed after human oral intake, rapidly and extensively converted to acyclovir and amino acid L-valine. Valacyclovir absorption is not altered by administration with food. 1-3 Valacyclovir was initially approved in USA in June 1995 and has indications for herpes simplex virus (HSV-1 and HSV-2) and varicella zoster virus infection. The Valacyclovir antiviral activity reflects its in vivo conversion to acyclovir. Acyclovir, which is a nucleoside analogue, is phosphorylated by virally-encoded thymidine kinase and subsequently by cellular enzymes, yielding acyclovir triphosphate, which competitively inhibits viral DNA polymerase so that viral DNA production is terminated. Valacyclovir has more favorable pharmacokinetics requiring less frequent dosing and achieving higher blood plasma levels than acyclovir. Valacyclovir, at a dose of 250 mg four times daily, generates an area under the concentration-time curve (AUC) of acyclovir orally at a dose of 800 mg five times daily. Valacyclovir, at a dose of 1,000 mg three times daily produces similar acyclovir AUC as intravenous (IV) acyclovir at a dose of 5 mg/kg every eight hours. 4,5 Valacyclovir can generally be regarded as an acceptable alternative to oral acyclovir when this drug is indicated and features a more convenient dosing schedule. Generally, Valacyclovir is well tolerated, similar to the experience with acyclovir. The product prescribing information contained warnings and precautions of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, acute renal failure and central nervous system adverse reactions. 2,3,6 Valacyclovir prescriptions in the USA outnumbered acyclovir at least since 2007 by 27% (3,339,913 vs. 2,627,727 prescriptions) and increased by 26.67% in the 10 years to 2017, while acyclovir prescriptions increased by 43.34% in the same period. 7 Acyclovir nephrotoxicity is explained by crystal nephropathy and acute interstitial nephritis mechanisms, but acute tubular necrosis can also occur. 8,9

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Valacyclovir Neurotoxicity and Nephrotoxicity in an Elderly Patient Complicated by Hyponatremia

Cited by 8 publications

References 38 publications

Concurrent Nephrotoxicity and Neurotoxicity Induced by Oral Valacyclovir in a Patient With Previously Normal Kidney Function

Concurrent Nephrotoxicity and Neurotoxicity Induced by Oral Valacyclovir in a Patient With Previously Normal Kidney Function

Neurotoxicity associated with acyclovir and valacyclovir: A systematic review of cases

Valacyclovir Non-Oliguric Acute Kidney Injury: a Case Report of 84 Year-Old Female

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