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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 2004  |  Volume : 15  |  Issue : 1  |  Page : 50-52
Neuropsychiatric Manifestations in a Patient Undergoing Hemodialysis Caused by Treatment with Oral Acyclovir


Department of Nephrology, Monastir Hospital, Monastir 5000, Tunisia

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   Abstract 

A 50-year-old woman who was being treated with hemodialysis was admitted for severe neuropsychiatric symptoms. She tested positive for antibody to hepatitis C virus. Her medical history revealed ophthalmic herpes zoster four days before her admission for which she was started on oral acyclovir (800 mg three times daily). Four days later, she became disoriented and agitated. She had visual hallucinations and myoclonus. She was diagnosed as having acyclovir toxicity and was instituted on vigorous dialysis. The serum acyclovir levels normalized and the patient became asymptomatic with three dialysis sessions. Our case further reinforces that the dose of acyclovir should be reduced in patients with renal failure and that dialysis is a good form of treatment for over dosage.

Keywords: Acyclovir, Hemodialysis, Toxicity.

How to cite this article:
Skhiri H, Achour A, Skhiri S, Frih A, Bouraoui S, Dhia NB, Elmay M. Neuropsychiatric Manifestations in a Patient Undergoing Hemodialysis Caused by Treatment with Oral Acyclovir. Saudi J Kidney Dis Transpl 2004;15:50-2

How to cite this URL:
Skhiri H, Achour A, Skhiri S, Frih A, Bouraoui S, Dhia NB, Elmay M. Neuropsychiatric Manifestations in a Patient Undergoing Hemodialysis Caused by Treatment with Oral Acyclovir. Saudi J Kidney Dis Transpl [serial online] 2004 [cited 2019 Sep 21];15:50-2. Available from: http://www.sjkdt.org/text.asp?2004/15/1/50/32965

   Introduction Top


Acyclovir is a widely used, generally well­tolerated antiviral agent. It is used with good success for herpetic infections. [1] Neurotoxicity associated with acyclovir use is infrequently encountered. It occurs more commonly with intravenous treatment than with oral treatment. The half-life of acyclovir is greatly prolonged in patients with end-stage renal disease, predisposing these patients to neurological side effects that are occasionally severe, but generally reversible. [2],[3] Thus, adjustment of the dose of acyclovir is recommended for patients with renal insufficiency and for those who are on hemodialysis (HD). [4]

We report a case of neuropsychiatric symp­toms in a patient undergoing HD who received acyclovir.


   Case Report Top


A 50-year-old woman who was on main­tenance HD presented with a vesicular rash on the left side of the face characteristic of herpes zoster infection.

She consulted a dermatologist and was initiated on treatment with oral acyclovir 2400 mg daily. She also received opthalmic pomade. Three days later, she presented with facial neuralgia. She was treated by carba­mazepine 200 mg daily. A day later, she developed severe neuro-psychiatric symptoms for which she was hospitalized. She was afebrile, confused, agitated with tonic-clonic movements of all extremities. She had slurred speech, visual hallucinations and facial neuralgia.

Neurological examination was unremarkable. Serum electrolytes, glucose, blood cell counts, transaminases and C reactive protein were normal. To eliminate the possibility of herpes zoster-associated encephalitis, a lumbar pun­cture was performed, and the cerebrospinal fluid (CSF) revealed no red or white blood cells, protein level of 200 mg/dl and glucose level of 63 mg/dl (the serum glucose level was 126 mg/dl). Gram stain and latex agglutination test for bacterial antigens were negative. A computerized tomographic scan of the brain was normal.

At this juncture, acyclovir associated enceph­alopathy was considered the most likely cause for the neuro-psychiatric picture.

Acyclovir was then stopped and acute long HD (6 hours) was performed. After the first HD session, there was rapid recovery from the neurological symptoms and on the fifth day, after the third HD session, neurological recovery was complete. The patient was discharged from the hospital six days after admission.

A double antibody radioimmunoassay with a monoclonal antibody to acyclovir was used to determine the acyclovir serum concentration. The level of acyclovir was extremely high even after the first HD session at 8.6 µg/ml which is 8.5 times higher than the recommended trough level (<1 µg/ml). After the second HD session, the acyclovir level was 0.15 µg/ml. These findings, with the favorable outcome after HD, confirmed acyclovir neurotoxicity.


   Discussion Top


Herpes Zoster infection in patients under­going HD is difficult to diagnose and treat and may have severe complications. The type 1 herpes simplex virus has neurologic tropism after reactivation from ganglions infected with asymptomatic primary infection. Serious ence-phalitis may occur. Patients undergoing HD may have variable clinical symptoms after herpes zoster infection and encephalitis has to be ruled out in all cases with atypical presentation.

Treatment with acyclovir, especially without dose adjustment, to patients with impaired renal function exposes them to side effects, [5],[6] particularly neurotoxicity. [7],[8] It is often difficult to distinguish between herpes zoster ence­phalitis and acyclovir neurotoxicity on the basis of clinical findings alone.

Acyclovir is mainly eliminated by the kidney. It is estimated that the bioavailability of an oral dose of acyclovir is 15 to 30%. Acyclovir's half-life is about three hours in adults with normal renal function but increases to 20 hours in patients with renal failure. Therefore, dose adjustments are recommended for this population. Thus, the recommended dose of acyclovir for patients undergoing HD is 800 mg per day orally and 5 mg/kg/day for intra­venous injection. [4]

Hemodialysis can remove up to 45% and 113 ml/min of the drug and this is considered a reasonable method to reduce the duration of toxicity. [9],[10],[11] It should also be noted that the resolution of the syndrome can be delayed by 48-72 hours after clearance of the drug. [8] Thus, the neurological recovery in our patient was complete after the third HD session despite the normalization of the acyclovir level after the second HD session.

Acyclovir neurotoxicity has been reported even in patients receiving doses considered adequate. [12],[13] This may be due to variable individual susceptibility to this drug.


   Conclusion Top


We have described a patient with neurotoxicity associated with high serum concentrations of acyclovir. It is imperative that patients with diminished renal function be dosed according to the recommended guidelines for acyclovir. In addition, close clinical monitoring for neurological side effects in these patients is necessary. Rapid recovery of encephalopathy can be achieved by early institution of daily HD.

 
   References Top

1.Auwerx J, Knockaert D, Hofkens P. Acyclovir and neurologic manifestations. Ann Intern Med 1983;99 (6) :882-3.  Back to cited text no. 1    
2.Peces R, de la Torre M, Alcazar R. Acyclovir-associated encephalopathy in haemodialysis. Nephrol Dial Transplant 1996;11(4):752.  Back to cited text no. 2    
3.Gomez Campdera FJ, Verde E, Vozmediano MC, Valderrabano F. More about acyclovir neurotoxicity in patients on haemodialysis. Nephron 1998;78(2):228-9.  Back to cited text no. 3    
4.Anonymous. Acyclovir in general practice. Drug Ther Bull 1992;30(26):101-4.  Back to cited text no. 4    
5.Collins A, Krieff D, Smith C, Singer C. Neuropsychiatric toxicity in a patient undergoing hemodialysis and receiving treatment with oral acyclovir. Clin Infect Dis 1996;22 (1):187-8.  Back to cited text no. 5    
6.Revankar SG, Applegate AL, Markovitz DM. Delirium associated with acyclovir treatment in a patient with renal failure. Clin Infect Dis 1995;21(2):435-6.  Back to cited text no. 6    
7.MacDiarmaid-Gordon AR, O'Connor M, Beaman M, Ackrill P. Neurotoxicity associated with oral acyclovir in patients undergoing dialysis. Nephron 1992;62(3): 280-3.  Back to cited text no. 7    
8.Haefeli WE, Schoenenberger RA, Weiss P, Ritz RF. Acyclovir induced neurotoxicity: concentration side effect relationship in acyclovir overdose. Am J Med 1993;94: 212-5.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Keller F, Giehl M, Frankewitsch T, Zellner D. Pharmacokinetics and drug dosage adjust­ment to renal impairment. Nephrol Dial Transplant 1995;10:1516-20.  Back to cited text no. 9    
10.Boulieu R, Bastien O, Gaillard S, Flamens C. Pharmacokinetics of acyclovir in patients undergoing continuous venovenous hemo­dialysis. Ther Drug Monit 1997;19(6):701- 4.  Back to cited text no. 10    
11.Leikin JB, Shicker L, Orlowski J, Blair AT, McAllister K. Hemodialysis removal of acyclovir. Vet Hum Toxicol 1995;37(3): 233-4.  Back to cited text no. 11    
12.Abad S, Deray G, Lokiec F, Hamani A, Petitclerc T, Jacobs C. Coma induced by intravenous acyclovir in a hemodialysed patient. Presse Med 1997;26 (22):1050.  Back to cited text no. 12    
13.Almond MK, Fan S, Dhillon S, Pollock AM, Raftery MJ. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron 1995;69 (4):428-32.  Back to cited text no. 13    

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Correspondence Address:
Habib Skhiri
Department of Nephrology, Monastir Hospital, Monastir 5000
Tunisia
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PMID: 18202466

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    Abstract
    Introduction
    Case Report
    Discussion
    Conclusion
    References
 

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