Clinical Review of Risk of Nephrotoxicity with Acyclovir Use for Treatment of Herpes Simplex Virus Infections in Neonates and Children

Objective: This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated.

Methods: Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children.

Results: There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m², older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated.

Conclusions: The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.