TOXICOLOGY QUESTION OF THE WEEK

November 17, 2023

Altered mental status can be caused by which drug used to treat Herpes Zoster (Shingles)?

Valacyclovir, of course.

Valacyclovir, a prodrug of acyclovir, is absorbed thru the intestine and undergoes extensive hepatic first-pass metabolism to form acyclovir. Oral acyclovir is rapidly metabolized, so plasma concentrations of acyclovir are much higher when valacyclovir is administered than when acyclovir is administered. Practically, this means fewer oral doses as plasma concentration can be maintained. (Acyclovir-5 doses a day; valacyclovir 1-2 doses a day.) Acyclovir is the part of valacyclovir that is incorporated into infected cells.

The kidneys are the primary route of elimination, and most of an oral dose of valacyclovir is excreted as acyclovir.

Not surprisingly, most cases (but not all) of acyclovir neurotoxicity occur in patients with renal impairment. Valacyclovir neurotoxicity is a clinical diagnosis. Encephalitis, CNS infections, and other causes of AMS must also be ruled out. One clinical factor that may help differentiate the diagnosis is that herpes encephalitis occurs one to two weeks after the onset of the vesicular skin eruptions, whereas acyclovir-induced AMS occurs approximately three days after the initiation of the drug.

Treatment is supportive, including discontinuation of the medication. Evaluation of renal function is crucial. Hemodialysis may shorten the duration of symptoms.

Question submitted by Donna Seger MD 

I am interested in any questions you would like addressed in the Question of the Week. Please email me with any suggestions at donna.seger@vumc.org.

DONNA SEGER, MD
Professor Emeritus
Department of Medicine
VUMC