Tamiflu Findings Raise Questions About Drug Label Warning for Kids

Treatment with the antiviral oseltamivir (Tamiflu) was tied to a reduced risk of serious neuropsychiatric events in children and adolescents, an analysis of Medicaid beneficiaries in Tennessee suggested.

Compared with untreated flu, the risk of serious neuropsychiatric events was lower in kids treated with oseltamivir during flu exposure periods (adjusted incidence rate ratio [IRR] 0.53, 95% CI 0.33-0.88) and post-treatment periods (adjusted IRR 0.42, 95% CI 0.24-0.74), reported James Antoon, MD, PhD, MPH, of Vanderbilt University in Nashville, Tennessee and colleagues.

Relative risks of neuropsychiatric events also were low during periods with neither flu exposure nor oseltamivir dispensing (adjusted IRR 0.08, 95% CI 0.06-0.11) and during oseltamivir prophylaxis periods (adjusted IRR 0.10, 95% CI 0.03-0.32) compared with untreated flu, the researchers wrote in JAMA Neurology.

“Influenza antivirals are safe and effective and should be used as early as possible during influenza illness. Yet, they are substantially underused, especially in children,” Antoon said.

“Almost 40% of children at high risk for influenza complications do not receive antiviral treatment. One important reason for this is concern about possible neuropsychiatric side effects,” he told MedPage Today.

“We found that influenza itself, rather than oseltamivir, is associated with neuropsychiatric events,” Antoon stated. “In fact, oseltamivir treatment lowered the risk of neuropsychiatric events in children by about 50%.”

The findings raise questions about warnings on oseltamivir’s label. Postmarketing surveillance in 2005 suggested an increase in serious neuropsychiatric events among children using oseltamivir, prompting the FDA to change oseltamivir’s warning label, Antoon and colleagues noted. Prescribing information for oseltamivir now states that some flu patients who receive the drug, particularly pediatric patients, may be at an increased risk of confusion or abnormal behavior early in their illness.

“It is important to note that these warnings were placed on the basis of case reports rather than studies on associated risks for these events,” Antoon and co-authors wrote.

The CDC and the American Academy of Pediatrics recommend antiviral treatment with drugs like oseltamivir for children with suspected or confirmed influenza who are hospitalized or have severe or progressive disease, or those who have underlying conditions that increase their risk of complications.

In their analysis, Antoon and colleagues studied children ages 5 to 17 years who were enrolled in Tennessee Medicaid during the 2016 to 2017 and 2019 to 2020 flu seasons.

The primary outcome was a neuropsychiatric event requiring hospitalization. The primary comparison for the study was treated flu versus untreated flu.

Each person-day of follow-up was assigned to one of five mutually exclusive exposure groups: (1) untreated flu, (2) treated flu, (3) post-treatment period (between oseltamivir completion and end of flu period), (4) flu prophylaxis, and (5) no exposure.

The cohort included 692,295 children (median age 11 years and 50.3% girls) who experienced 1,230 serious neuropsychiatric events during 19,688,320 person-weeks of follow-up. Clinical characteristics were generally similar across exposure groups.

There were 129,134 children and 151,401 flu episodes. Among kids with a flu episode, 66.7% were dispensed oseltamivir; most were dispensed the drug the same day as their flu diagnosis. Among children at high risk for flu complications, 60.1% received an antiviral.

Overall, the most common serious neuropsychiatric events in the study were mood disorders (36.3%) and suicidal or self-harm behaviors (34.2%), followed by seizures (13.7%). Seizures (34.1%) were the most common events during flu exposure periods.

Secondary analyses suggested the study’s findings were driven more by a reduction in neurologic events (adjusted IRR 0.45, 95% CI 0.25-0.83) than psychiatric events (adjusted IRR 0.80, 95% CI 0.34-1.88) among oseltamivir-treated children.

The analysis did not account for influenza strain or vaccination status, which are not reliably captured in databases, the researchers acknowledged.

The study focused on neuropsychiatric events that required hospitalization, they added. Findings might not apply to children outside of Tennessee’s pediatric Medicaid population.

MedPage Today. She writes about brain aging, Alzheimeru2019s disease, dementia, MS, rare diseases, epilepsy, autism, headache, stroke, Parkinsonu2019s disease, ALS, concussion, CTE, sleep, pain, and more. Judy started her career with the Congressional watchdog agency GAO and has been a magazine reporter, academic text editor, and radio producer. She holds a BA in English from University of Detroit, MBA from Xavier University, and attended Columbia Radcliffe Publishing Course. Besides writing about neurology, sheu2019s reported on topics ranging from mental health to environmental contamination. Her work has been published in outlets as diverse as Business Week, Conde Nast’s Self, and AlterNet.”,”affiliation”:””,”credential”:””,”url_identifier”:”jg8109″,”avatar_url”:””,”avatar_alt_text”:”Judy George”,”twitter”:”https://twitter.com/MedPageNeuro”,”byline”:”Deputy Managing Editor, MedPage Today”,”full_name”:”Judy George”,”title”:”Deputy Managing Editor, MedPage Today, “,”url”:”https://www.medpagetoday.com/people/jg8109/judy-george”}]”>