Inappropriate Valacyclovir Dosing by Renal Function in Japan

Valacyclovir requires dose adjustment according to renal function to prevent serious adverse events. However, real-world data on renal function-based dosing practices are limited.

To evaluate the frequency of valacyclovir overdosing according to renal function and to identify the characteristics associated with overdosing in Japan.

We conducted a retrospective cohort study using a nationwide database of administrative claims and laboratory results from acute care hospitals in Japan. We included adults aged ≥18 years who received at least 1 valacyclovir prescription between October 1, 2022, and September 30, 2024, and who had a serum creatinine measurement within the preceding year. The primary outcome was overdosing, defined as a prescribed dose that exceeded the maximum recommended dose for the patient's renal function level per the Japanese package insert. Renal function was estimated using creatinine clearance calculated with the Cockcroft-Gault equation.

A total of 6764 patients with 7901 valacyclovir prescriptions were included; 1649 prescriptions (20.9%) were for patients with impaired renal function. Overdosing was rare among patients with normal renal function. Among patients with impaired renal function, overdosing occurred in 25.1% of prescriptions for varicella or herpes zoster and in 6.4% for other indications. Overdosing was more frequent among women and most common for prescriptions dispensed at community pharmacies.

In this nationwide study, valacyclovir overdosing was common among patients with impaired renal function, particularly for high-dose indications, and occurred more frequently among women and for prescriptions dispensed at community pharmacies. Strengthening renal function-based prescription review may help reduce preventable overdosing.