From the Guidelines
Acyclovir in neonates can cause several side effects, but the benefits of treatment for herpes infections typically outweigh the risks, and high-dose intravenous acyclovir (20 mg/kg body weight/dose three times daily) is recommended for 21 days for CNS and disseminated disease and for 14 days for skin, eye, and mouth disease 1. The most common side effects of acyclovir in neonates include:
- Renal impairment, particularly with high doses or dehydration
- Phlebitis at IV injection sites
- Transient neutropenia Neurological side effects such as tremors, lethargy, or seizures may occur, especially with renal dysfunction or high serum levels 1. Gastrointestinal effects like nausea, vomiting, or diarrhea are possible but less common in neonates. Rarely, acyclovir can cause acute kidney injury, thrombocytopenia, or elevated liver enzymes. To minimize these risks, ensure proper hydration, adjust dosing for gestational age and renal function, monitor complete blood counts, renal function, and liver enzymes during treatment, and observe IV sites for signs of inflammation. These precautions are particularly important because neonates have immature renal function and drug clearance mechanisms, making them more susceptible to medication side effects. The use of high-dose acyclovir in neonates with herpes simplex encephalitis has decreased mortality to 5%, with ∼40% of survivors developing normally 1. Monitoring for potential side effects and adjusting treatment as needed is crucial to minimize risks and optimize outcomes in neonates treated with acyclovir.
From the FDA Drug Label
The adverse reactions listed below have been observed in controlled and uncontrolled clinical trials in approximately 700 patients who received acyclovir at approximately 5 mg/kg (250 mg/m2) three times daily, and approximately 300 patients who received approximately 10 mg/kg (500 mg/m2) three times daily The most frequent adverse reactions reported during administration of acyclovir were inflammation or phlebitis at the injection site in approximately 9% of the patients, and transient elevations of serum creatinine or BUN in 5% to 10% Nausea and/or vomiting occurred in approximately 7% of the patients Itching, rash, or hives occurred in approximately 2% of patients. Elevation of transaminases occurred in 1% to 2% of patients The following hematologic abnormalities occurred at a frequency of less than 1%: anemia, neutropenia, thrombocytopenia, thrombocytosis, leukocytosis, and neutrophilia. In addition, anorexia and hematuria were observed
The FDA drug label does not answer the question about Acyclovir side effects in neonates, as the provided text does not specifically mention neonates. 2
From the Research
Acyclovir Side Effects in Neonates
- The most common clinical adverse events (AEs) associated with acyclovir treatment in neonates include hypotension and seizure, both occurring in 9% of infants 3.
- Thrombocytopenia is the most common laboratory AE, occurring in 25% of infants and on 9% of infant-days 3.
- Elevated creatinine occurs in 2% of infants and 0.2% of infant-days, with no infants developing renal failure requiring dialysis 3.
- Neutropenia is a potential AE, with 21% of high-dose acyclovir recipients experiencing this condition, although it is usually transient and resolves with continued treatment or after completion of therapy 4.
- Rash is a common clinical AE, occurring in 37% of infants treated with high-dose acyclovir 5.
- Mild laboratory AEs, such as hypokalemia, elevated blood urea nitrogen, and thrombocytosis, occur in 2-37% of infants 5.
- Acyclovir exposure is not associated with an increased risk of adverse events, including clinical and laboratory AEs 5.
Acyclovir Dosage and Administration
- High-dose acyclovir (60 mg/kg/d) is recommended for the treatment of neonatal herpes simplex virus disease, although this dosage is not currently approved by the US Food and Drug Administration 3.
- The standard dosage of acyclovir is 20 mg/kg/dose intravenously every 8 hours, although this may be increased to 30 mg/kg/dose every 8 hours in certain situations 6.
- Continuous-infusion acyclovir may be effective in achieving therapeutic drug concentrations in neonates receiving extracorporeal life support and continuous renal replacement therapy 6.
- Oral acyclovir suspension is approved for the treatment of herpes simplex virus and varicella-zoster virus infections in children, with a recommended dosing regimen of 24 mg/kg of body weight three times a day for patients younger than 1 month of age or four times a day otherwise 7.