Valacyclovir: An overview
- Kimon C Zachary, MD
Kimon C Zachary, MD
- Assistant Professor of Medicine
- Harvard Medical School
Valacyclovir is the valyl ester of the antiviral drug acyclovir . Acting as an oral prodrug, valacyclovir is converted in vivo to acyclovir. Acyclovir, a nucleoside analog, is phosphorylated by virally-encoded thymidine kinase and subsequently by cellular enzymes, yielding acyclovir triphosphate, which competitively inhibits viral DNA polymerase. (See "Acyclovir: An overview".)
The antiviral activity of valacyclovir reflects its in vivo conversion to acyclovir, which is active against herpes simplex viruses types 1 and 2, varicella-zoster virus, and Epstein-Barr virus. Cytomegalovirus (CMV), which does not encode thymidine kinase, is resistant at the oral doses approved by the US Food and Drug Administration [2,3].
Valacyclovir has three to fivefold greater oral bioavailability (about 55 percent) than acyclovir; it then undergoes rapid and extensive first-pass intestinal and/or hepatic hydrolysis to yield acyclovir and L-valine [2,3]. Food does not affect absorption.
Valacyclovir, at a dose of 250 mg four times daily, generates essentially the same acyclovir AUC (area under the curve, or exposure over 24 hours) as oral acyclovir at a dose 800 mg five times daily . Valacyclovir, at a dose of 1000 mg three times daily, produces a similar acyclovir AUC as intravenous acyclovir at a dose of 5 mg/kg every eight hours .
Intravenous acyclovir generates higher peak levels than oral valacyclovir. Although this feature may confer more potent activity, it may also increase the risk of renal toxicity due to precipitation of acyclovir crystals in the renal tubules  (see "Crystal-induced acute kidney injury (acute renal failure)"). On the other hand, the safety of high-dose oral valacyclovir, especially in immunocompromised persons, remains controversial.
- Valtrex (valacyclovir hydrochloride) prescribing information, Glaxo Wellcome Inc, 2013. https://www.gsksource.com/gskprm/htdocs/documents/VALTREX-PI-PIL.PDF.
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