Tamiflu Linked to Abnormal Behavior:
Delirium and Suicide

The flu drug's maker warns of such potential problems as suicide

JIA-RUI CHONG / Los Angeles Times 14nov2006

The maker of the antiviral medication Tamiflu issued a new warning for the flu drug Monday, saying patients must be closely monitored for potential psychiatric problems, including delirium and suicide.

Hoffman-La Roche Inc. had been discussing the matter with the Food and Drug Administration, which has been reviewing 103 cases in which patients reported bizarre behavior, usually within a day of taking Tamiflu.

Most cases involved children under 17 and occurred in Japan. The cases include three people who fell to their deaths after taking the drug, including a 14-year-old boy who climbed atop the railing of his family's condominium, an FDA memo says.

The memo also cites the case of an 8-year-old in Japan who took one dose of Tamiflu and, about an hour and a half later, tried to run out the front door of his home. The child would not answer to his name and was growling, according to the memo, which was prepared in advance of an FDA pediatric advisory committee meeting Thursday.

Dr. Debra Birnkrant, director of the FDA's division of antiviral products, said it was not yet known if the abnormal behavior was caused by the drug or the flu, which can cause fever and delirium.

But she added, "Since there were a number of cases over the last year that we looked at, we thought it would be the prudent thing to make the public aware."

Another drug for seasonal flu, amantadine, has been associated with similar neurological side effects, mostly in the elderly, Birnkrant said.

Hoffman-La Roche said in a statement that reports of psychiatric side effects from Tamiflu were rare. "While any relative contribution of Tamiflu to these events is unknown, Roche is committed to working closely with the FDA to ensure that the product label accurately reflects the reports," it said.

The FDA's memo says 24.5 million Tamiflu prescriptions were filled in Japan from 2001 to 2005. In the U.S., 6.5 million prescriptions were filled in the same period.

Tamiflu is one of four treatments for seasonal flu in the U.S. It is usually taken to prevent or lessen the severity of the virus.

Many governments, including that of the U.S., have stockpiled the drug to combat a possible outbreak of the H5N1 avian influenza virus. Although that mainly infects birds, there have been 153 human deaths worldwide since 2003, according to the World Health Organization.

source:  14nov2006

FDA Posts New Tamiflu Warning

MIRANDA HITTI / WebMD Medical News 14nov2006

The FDA has announced a new warning for the flu drug Tamiflu.

The new warning notes reports of self-injury and delirium in flu patients taking Tamiflu, mainly among children in Japan.

The FDA knows of 103 reported cases -- 95 from Japan, five from the U.S., and three from other countries. Sixty of the 103 cases featured delirium with prominent behavioral disturbance such as panic attack, hallucinations, and convulsions; only one of those cases occurred in the U.S.

It's not known if Tamiflu caused any of those events.

"People with the flu, particularly children, may be at an increased risk of self-injury and confusion shortly after taking Tamiflu and should be closely monitored for signs of unusual behavior," states Tamiflu's new warning.

"Patients with influenza should be closely monitored for signs of abnormal behavior throughout the treatment period," the warning also notes.

"A healthcare professional should be contacted immediately if the patient taking Tamiflu shows any signs of unusual behavior," states the warning.

The drug company Roche, which makes Tamiflu, sent a letter dated Nov. 13 to health care workers about the new warning. Roche is a WebMD sponsor.

In a Roche news release, the drug company states that "while any relative contribution of Tamiflu to these events is unknown, Roche is committed to working closely with the FDA to ensure that the product label accurately reflects the reports, so that healthcare professionals, as well as parents and guardians, can closely monitor influenza patients for any signs of abnormal behavior."

About Tamiflu

Tamiflu is an oral flu treatment. It does not prevent flu. Instead, it lessens the severity of symptoms and shortens recovery time by one to two days. Tamiflu works best if it is taken within 48 hours of the first symptoms of flu.

Tamiflu was approved in 1999 and has been used by more than 42 million people in over 80 countries, Roche states.

Roche and the FDA continue to monitor Tamiflu safety.

Any adverse events with Tamiflu should be reported to the FDA's MedWatch program by phone at (800) FDA-1088 ((800) 332-1088) or online at www.fda.gov/medwatch.

Adverse events with Tamiflu may also be reported to Roche by phone at (800) 526-6367 or by fax at (800) 532-3931.

SOURCES: News release, FDA. Crystal Rice, FDA spokeswoman. Roche, "Patient Information, Tamiflu." Roche, "Dear Health Care Professional," Nov. 13, 2006. News release, Roche. WebMD Drug Information from First DataBank: "Tamiflu Oral."

source: http://www.webmd.com/content/article/129/117515.htm 14nov2006

FDA Urges Caution on Flu Drug

PATRICIA KOWSMANN / Wall Street Journal 14nov2006

WASHINGTON -- Food and Drug Administration staff recommended that the label for Roche Holding AG's flu drug Tamiflu be updated to include a precaution related to possible psychiatric problems in patients who take it.

The move follows a 10-month review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on a balcony railing.

Of the cases, 67% were in children and 95% occurred outside the U.S., mostly in Japan, Tamiflu's biggest consumer. Two other related deaths by people who took Tamiflu were reported, including an adult who left a suicide note.

The officials still don't know if the new cases, reported from August 2005 to July, are linked to the drug, to the flu virus, or a combination of the two.

In Japan, Tamiflu's label already carries information on such events.

"Roche continuously reviews post-marketing safety information, and as a result, has agreed with the FDA that the Tamiflu label be revised to include reports of neuropsychiatric events such as self-injury and delirium in patients with influenza," a Roche statement said.

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