Oseltamivir Adverse Events

Psychiatric Symptoms Associated with Oseltamivir 

Now that influenza activity is starting to pick up, although still below normal for this time of year, the November 29 Health Canada advisory on psychiatric symptoms with oseltamivir is worth revisiting. As covered in the media in December 2005 and in November 2006, there have been reports of hallucinations and abnormal behavior, including self-harm, in patients taking oseltamivir (Tamiflu®). These reports, which include children and teenagers, come mostly from Japan, which uses the most oseltamivir in the world. The Health Canada advisory cites 84 people in Canada with adverse events while taking oseltamivir, of whom 7 had psychiatric symptoms, although it has not yet been determined if oseltamivir caused or contributed to any of these events.

The FDA warns that stopping oseltamivir could be harmful if influenza itself is causing delirium, hallucinations and other abnormal behaviour, such as aggression and suicidal thoughts. In one study of children with influenza in Houston, Texas, Maricich et al reported that “Neurologic symptoms and sequelae were associated with influenza A virus infection in children . . . . Influenza should be considered in the differential diagnosis in patients with seizures and mental status changes, especially if they present with respiratory symptoms or during an influenza outbreak.” (http://pediatrics.aappublications.org/cgi/content/abstract/114/5/e626) As Osler said, “Almost every form of disease of the nervous system may follow influenza.” (http://archpsyc.ama-assn.org/cgi/reprint/63/4/354.pdf).

Although we are not using amantadine this season, we should remember that amantadine is more likely to cause psychiatric symptoms in the elderly than is oseltamivir, especially with high plasma drug concentrations. Most at risk are those with renal insufficiency, seizure disorders, or certain psychiatric disorders, and among elderly persons taking amantadine as prophylaxis at a dose of 200 mg/day.

Health Canada estimates that 10-25% of Canadians (i.e., 3 to 8 million) may get the flu each year and between 4,000 to 8,000 Canadians die every year from pneumonia related to flu. As always, defenses against influenza include hand washing, hand sanitizing, not going to work when ill, and especially vaccination. For anyone who hasn’t had a flu shot yet and needs one, now is a good time.