# Trends in Linezolid Prescription in Japan based on National database open Data: implications for the need for therapeutic drug monitoring

## TL;DR

This study examines how linezolid is prescribed in Japan, finding it is mainly used by older adults, raising concerns about safety due to potential toxicity.

## Contribution

The study provides real-world insights into linezolid prescription trends in Japan, emphasizing the need for monitoring in high-risk populations.

## Key findings

- Inpatient linezolid use declined from 2014 to 2023, while outpatient use remained low but showed some increase in 2022.
- Prescriptions were concentrated among older adults, especially those aged 85–89, who are at higher risk for toxicity.
- Outpatient oral use was almost exclusively observed in older adults, suggesting a need for careful monitoring in this group.

## Abstract

Linezolid is an oxazolidinone antibiotic widely used to treat infections caused by resistant Gram-positive bacteria. It has long been regarded as a drug that does not require therapeutic drug monitoring, owing to its limited pharmacokinetic variability. However, recent clinical observations suggest that delayed linezolid elimination is associated with hematological toxicity and thrombocytopenia, particularly in older adults and individuals with reduced renal function. As Japan has a rapidly aging population, understanding real-world linezolid prescription patterns is important for contextualizing potential safety concerns related to its use.

This study analyzed Japanese national linezolid prescription trends using publicly available data from the National Database of Health Insurance Claims. The annual prescription counts of oral and parenteral linezolid formulations were descriptively examined in inpatient and outpatient settings, along with age- and sex-specific distributions. To provide comparative context, inpatient trends in parenteral use of major anti- methicillin-resistant Staphylococcus aureus (MRSA) agents were also assessed using the same data source.

Inpatient use declined steadily from 2014 to 2023. Outpatient use remained extremely limited for most of the study period; however, oral outpatient prescriptions became observable from 2022 onward, though the absolute magnitude remained small. Given that outpatient care generally involves less intensive clinical monitoring, even limited outpatient use warrants careful interpretation. Age-stratified analysis revealed that prescriptions were concentrated among older adults, with the highest use observed in individuals aged 85–89 years. These patients are more likely to have reduced renal function, which can further increase drug exposure and the risk of toxicity. Stratified analyses further demonstrated that outpatient oral use was almost exclusively observed among older adults. In the comparative inpatient analysis of parenteral anti-MRSA agents, trends differed by agent, indicating that the decline in linezolid use did not simply reflect uniform changes in inpatient anti-MRSA antibiotic utilization.

These national prescribing patterns indicate that linezolid continues to be used predominantly among older adults. Although causal relationships cannot be inferred from this descriptive analysis, the findings highlight clinical contexts in which careful monitoring of linezolid therapy may be particularly important. Further evaluation is warranted to determine whether monitoring strategies, including the potential role of therapeutic drug monitoring, could contribute to safer use of linezolid in high-risk patient populations.