acyclovir and Drug-Overdose

To investigate the concentration-side effect relationship in a patient with severe acyclovir-induced neurotoxicity and to summarize the information available in the literature about central nervous system side effects due to acyclovir.. Repeated blood samples were drawn in a patient with severe acyclovir overdose who developed coma and nonoliguric renal failure. The acyclovir levels measured by radioimmunoassay were related to the level of consciousness.. We measured the highest acyclovir serum levels reported so far (229.9 mumol/L = 51.8 mg/L). Impairment of consciousness developed with a remarkable temporal delay of 24 to 48 hours after occurrence of peak serum concentrations and resolved with a comparable delay after reaching the therapeutic range (anticlockwise hysteresis). Six days after discontinuation of the drug, central nervous system symptoms had resolved, and, 4 days later, renal function returned to pretreatment values.. The observation that neurotoxicity developed with a delay of 24 to 48 hours after acyclovir peak serum concentrations could explain the wide range of acyclovir levels reported in similar cases. Single drug level measurements may therefore be of little diagnostic value. Since toxicity develops with a remarkable delay, early removal of the drug (by hemodialysis) could possibly prevent central nervous toxicity.

Topics: Acyclovir; Aged; Brain; Drug Overdose; Electroencephalography; Female; Herpes Zoster Ophthalmicus; Humans; Kidney; Time Factors; Unconsciousness

Topics: Academic Medical Centers; Accidents, Home; Acyclovir; Adult; Antiviral Agents; Boston; Combined Modality Therapy; Diagnosis, Differential; Drug Overdose; Emergency Service, Hospital; Fellowships and Scholarships; Female; Humans; Medical Staff, Hospital; Neurotoxicity Syndromes; Prodrugs; Status Epilepticus; Toxicology; Treatment Outcome; Valacyclovir; Valine; Workforce; Young Adult

Topics: Acute Kidney Injury; Acyclovir; Antiviral Agents; Crystallization; Drug Overdose; Humans; Male; Middle Aged; Uric Acid; Valacyclovir; Valine

Topics: Acyclovir; Aged; Akathisia, Drug-Induced; Alcoholic Intoxication; Baclofen; Continuity of Patient Care; Diagnostic Errors; Drug Overdose; Emergencies; Herpes Zoster; Humans; Kidney Failure, Chronic; Male; Muscle Relaxants, Central; Myoclonus; Poisoning; Renal Dialysis; Tremor; Uremia

We report three cases of neurotoxicity in patients with renal failure, treated with Zelitrex (valacyclovir).. 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.. 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.

Topics: Acyclovir; Aged; Aged, 80 and over; Biological Availability; Drug Overdose; Female; Humans; Male; Mental Disorders; Prodrugs; Renal Insufficiency; Valacyclovir; Valine

Topics: Acute Kidney Injury; Acyclovir; Aged; Antiviral Agents; Coma; Drug Overdose; Herpes Zoster; Humans; Male; Sleep Stages