Klin Farmakol Farm. 2022;36(4):129-135 | DOI: 10.36290/far.2022.021

The importance of therapeutic drug monitoring in acyclovir dosage optimization

Ivana Kacířová^{1, 2}, Romana Uřinovská¹, Jiří Sagan³

¹ Oddělení klinické farmakologie, Ústav laboratorní medicíny, Fakultní nemocnice Ostrava

² Ústav klinické farmakologie, Lékařská fakulta, Ostravská univerzita

³ Klinika infekčního lékařství, Fakultní nemocnice Ostrava

Acyclovir is an antiviral drug used to prevent and treat infections caused by herpes viruses such as herpes simplex virus and varicella-zoster virus. It is intracellularly phosphorylated into triphosphate nucleotides that inhibits viral DNA polymerase. Approximately 5-15 % of acyclovir is metabolized to the main metabolite 9-(carboxymethoxymethyl) guanine (CMMG), the main route of acyclovir elimination is renal excretion, which involves glomerular filtration and active tubular secretion. Accumulation of acyclovir and CMMG may occur in patients with impaired renal function. Acyclovir is often used and has good general tolerance, however, it can cause systemic adverse effects such as nephrotoxicity and neurotoxicity. Preexisting kidney disease, older age, obesity, hypertension, longer duration of treatment, and concurrent use of nephrotoxic drugs are associated with an increased risk of acyclovir-induced nephrotoxicity. The most characteristic symptoms of neurotoxicity are confusion, somnolence, and hallucinations. Symptoms of neurotoxicity caused by acyclovir treatment may be misinterpreted as symptoms of herpetic encephalitis. Accurately distinguishing between these two causes of neuropsychiatric symptoms is particularly important given the different treatment strategies. Determination of CMMG serum concentrations can help to differentiate between neuropsychiatric side effects of acyclovir and symptoms of any form of encephalitis. The wide interindividual variability of acyclovir pharmacokinetics can lead not only to toxicity but also to suboptimal therapeutic concentrations of acyclovir in severe herpes viruses infections. Therapeutic monitoring of acyclovir and CMMG can be a useful tool for optimizing pharmacotherapy with this antiviral, especially in patients with severe clinical conditions.

Keywords: acyclovir, 9-(carboxymethoxymethyl) guanine, concentrations, monitoring.

Accepted: February 8, 2023; Published: February 8, 2023  Show citation