Letter to the Editor
Neurotoxicity secondary to valacyclovir
Neurotoxicidad por valaciclovir
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It undergoes a first-pass liver metabolism, and it is almost entirely eliminated via the kidneys.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Its less common adverse reactions include neurotoxicity,<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> which occurs especially in elderly patients and with kidney failure; it is therefore an entity to be taken into account in neurological conditions in this type of patient.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of an 86-year-old man with a personal history of arterial hypertension, type 2 diabetes mellitus, peripheral arterial disease, and end-stage renal disease on regular haemodialysis (3 times a week), who began with painful vesicular lesions on the scalp compatible with herpetic infection, with valacyclovir being prescribed at a dose of 1<span class="elsevierStyleHsp" style=""></span>g/8<span class="elsevierStyleHsp" style=""></span>h. He went to the emergency department 48<span class="elsevierStyleHsp" style=""></span>h later for acute neurological symptoms consisting of alteration and fluctuation of the level of consciousness, dysarthria, ataxia, and visual hallucinations, with progressive worsening. A moderate elevation of C-reactive protein (89<span class="elsevierStyleHsp" style=""></span>mg/L) and pyuria (100<span class="elsevierStyleHsp" style=""></span>WBC/μL) stood out in the ancillary tests carried out, without abnormal hematimetry parameters. Given the initial suspicion of stroke, a brain computed tomography was performed, which showed only cortical atrophy and chronic lacunar lesions, without acute lesions. In view of the clinical improvement during his stay in observation, he was discharged with the addition of amoxicillin/clavulanic acid to treat a possible urinary tract infection.</p><p id="par0015" class="elsevierStylePara elsevierViewall">24<span class="elsevierStyleHsp" style=""></span>h later, he returned to the emergency department for recurrence of neurological symptoms, mainly fluctuations in the level of consciousness, agitation, and visual hallucinations. It was decided to expand the study, performing an electroencephalogram that only showed findings compatible with diffuse encephalopathy without data on epileptiform activity, as well as lumbar puncture, with normal biochemical and microbiological determinations.</p><p id="par0020" class="elsevierStylePara elsevierViewall">After having reasonably ruled out other causes of the condition, the possibility of neurotoxicity due to valaciclovir was considered as the cause of the process, deciding together with Nephrology an additional session of haemodialysis and readjustment of the valaciclovir regimen at discharge according to renal function (500<span class="elsevierStyleHsp" style=""></span>mg/24<span class="elsevierStyleHsp" style=""></span>h) until the treatment was completed. The patient continued with his routine haemodialysis sessions and 4 days later, complete remission of the neurological condition was achieved. After applying the Naranjo causality algorithm to our case, a level of probable causality was obtained (7 points), for which this event was reported to the National Pharmacovigilance System.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Valaciclovir, the prodrug of acyclovir with the highest oral bioavailability, has an elimination half-life of 3<span class="elsevierStyleHsp" style=""></span>h in patients with normal kidney function, reaching 14<span class="elsevierStyleHsp" style=""></span>h in the case of severe kidney failure.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> It has a high clearance in haemodialysis due to its low molecular weight and low binding to plasma proteins; however, peritoneal dialysis is not effective in these cases.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Its most common adverse reactions are nausea, headache, or skin rash. Much rarer, there are also severe haematological and renal conditions (thrombotic purpura, haemolytic uremic syndrome…). Likewise, neurological symptoms may appear in a very small percentage of patients.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Valacyclovir neurotoxicity was described in 1998,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> with few cases described in the literature as it is a very rare entity.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> There is a greater risk in renal failure and advanced age, so caution should be exercised in terms of dosage and the onset of symptoms in these 2 groups, as was the case in our patient. Infectious encephalitis, ischaemic stroke, epileptiform pathology, intracranial haematoma, or space-occupying lesions should be ruled out in the differential diagnosis, mainly because of their greater severity. The symptoms are highly variable: agitation, tremor, confusion, somnolence, ataxia, dysarthria, hallucinations, psychotic symptoms, seizures and even coma. It usually starts 48–72<span class="elsevierStyleHsp" style=""></span>h after initiation of treatment and resolves within 4 days after discontinuation, although, in some cases, it can take up to 14 days.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The recommended dose in case of herpes zoster regarding a clearance <<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>mL/min is 500<span class="elsevierStyleHsp" style=""></span>mg/day.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Treatment, once other aetiologies have been ruled out, is mainly based on drug discontinuation and, in cases that require it, haemodialysis for a significant reduction in drug levels.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Rosales-Castillo A, López-González Gila JD, Clavero García E. Neurotoxicidad por valaciclovir. Med Clin (Barc). 2021;156:361–362.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fichas técnicas del Centro de Información online de Medicamentos de la AEMPS–CIMA [base de datos en Internet]" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Valaciclovir" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2008" "editorial" => "Agencia española de medicamentos y productos sanitarios (AEMPS)" "editorialLocalizacion" => "Madrid, España" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.K. 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Selgas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.nefro.2017.05.007" "Revista" => array:6 [ "tituloSerie" => "Nefrologia" "fecha" => "2018" "volumen" => "38" "paginaInicial" => "323" "paginaFinal" => "325" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29523376" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015600000007/v1_202104020834/S2387020621000917/v1_202104020834/en/main.assets" "Apartado" => array:4 [ "identificador" => "43309" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the Editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015600000007/v1_202104020834/S2387020621000917/v1_202104020834/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020621000917?idApp=UINPBA00004N" ]
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