Risk of neuropsychiatric adverse events associated with the use of oseltamivir: a nationwide population-based case-crossover study

• Published in: Journal of antimicrobial chemotherapy Vol. 74; no. 2; pp. 453 - 461
• Main Authors: Kang, Hye-Rim, Lee, Eui-Kyung, Kim, Woo Jung, Shin, Ju-Young
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-02-2019
• Subjects: Adolescent; Adult; Aged; Antiviral Agents - adverse effects; Child; Child, Preschool; Cohort Studies; Cross-Over Studies; Female; Humans; Incidence; Infant; Infant, Newborn; Influenza, Human - drug therapy; Male; Mental Disorders - chemically induced; Middle Aged; Oseltamivir - adverse effects; Population Health; Republic of Korea; Risk Factors; Young Adult; Republic of Korea
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dky445

Abstract
Background
Although the potential risk of neuropsychiatric adverse events (NPAEs) upon administration of oseltamivir has been raised in case reports, the association between the use of oseltamivir and the risk of NPAEs is unclear.
Objectives
We aimed to evaluate whether the use of oseltamivir triggers NPAEs.
Patients and methods
We conducted a population-based case-crossover study using the National Sample Cohort data from the National Health Insurance Service in South Korea. From a total of 236 348 incident patients with NPAEs as either a primary or secondary diagnosis, our final case series included 5322 patients with a prior prescription for oseltamivir between 2009 and 2013. Exposure to oseltamivir was assessed during 2, 7, 14, 28 and 56 day hazard periods prior to each patient’s NPAE. Three pre-consecutive control periods were matched using the same time windows. Conditional logistic regression analysis was used to estimate adjusted ORs (aORs), adjusting for time-variant diagnosis of influenza and concomitant medications.
Results
Matched analyses found a consistently increased risk of NPAEs associated with the use of oseltamivir in the 2 day (aOR 1.90, 95% CI 1.29–2.81), 7 day (aOR 1.32, 95% CI 1.00–1.74), 14 day (aOR 1.28, 95% CI 1.03–1.60), 28 day (aOR 1.25, 95% CI 1.06–1.47) and 56 day (aOR 1.13, 95% CI 0.99–1.29) hazard periods compared with use in the three control periods.
Conclusions
This study found that the short-term use of oseltamivir triggers the incidence of NPAEs. Early monitoring of NPAEs may be required when prescribing oseltamivir with careful consideration of the risk–benefit balance of oseltamivir.