Japanese to study behavioral effects of Tamiflu

Jun 20, 2007 (CIDRAP News) – The company that markets oseltamivir (Tamiflu) in Japan has announced it will launch new studies to explore whether the antiviral drug contributes to adverse psychiatric and neurologic events in teenagers.

Meanwhile, experts at an international influenza conference this week in Toronto reported some progress in the quest for new types of antiviral drugs for flu patients, and Vietnam said it was ready to launch a trial of a locally made human vaccine for H5N1 avian flu.

Teen deaths prompt new studies
In aJun 18 news release, Chugai Pharmaceutical Co. said it has received several reports of serious psychiatric or neurologic events since oseltamivir's 2001 launch in Japan. Though no link between the adverse events and the drug was established, in May 2004 Chugai added information about the reported symptoms to its packing inserts. The company imports oseltamivir from Roche and markets it in Japan.

Four months ago Chugai said it received a report of two teenage flu patients who fell to their deaths after taking oseltamivir, the press release said. After the accidents, Japan's health ministry warned that children with the flu could show adverse behavioral effects, whether or not they were receiving oseltamivir, and advised doctors to avoid prescribing it to teenagers.

Oseltamivir, a neuraminidase inhibitor, is used for both treatment and prevention. Because world health experts regard it as the best available drug for combating a potential pandemic flu strain, the United States and numerous other countries are stockpiling it.

Chugai said it is examining adverse event reports to determine if any patterns emerge in the patient histories, timing of the drug, or onset of any abnormal behaviors.

Also, following Japanese health ministry proposals, Chugai and Roche will immediately conduct new research on the drug's safety. In preclinical trials, the companies will use rats to gauge the drug's effects on the brain, the press release said. A clinical research arm of the studies will assess the effect of oseltamivir on subjects' sleep and look at transport of the drug to the cerebrospinal fluid.

Chugai also will proceed with epidemiologic studies of patients treated with oseltamivir, to examine what other drugs they take, their flu symptoms and clinical course, and their medical history. The company said its goal is to use the studies to guide safety measures for the next flu season.

A 2006 report by the US Food and Drug Administration concluded it was unclear if neuropsychiatric events in those treated with oseltamivir were related only to the drug, only to the flu, or to both.

In previous statements, Roche has said that clinical trials in the United States and Japan showed similar rates of psychiatric symptoms in children with flu who took oseltamivir and in peers who didn't take it. The company also said US health insurance data showed that patients treated with the drug had a lower likelihood of events such as delirium, confusion, and hallucination than patients who were not treated.

Researchers discuss what's on the antiviral horizon
In presentations at the Options for the Control of Influenza Conference in Toronto yesterday, researchers offered glimpses of potential new antiviral medications, according to a Jun 19 Canadian Press (CP) report.

Frederick Hayden, MD, an antiviral expert with the World Health Organization (WHO), said work on new classes of antivirals drugs may eventually make the world less vulnerable to flu than it is now, with only four drugs in two classes available.

"The pipeline is not full, but it's certainly more robust than it was some years ago," Hayden told CP.

Later this week at the conference, researchers will present their work on a new drug, currently called T705, which targets the polymerase protein, a new target for flu antivirals, the CP story said. Hayden said phase 2 clinical trials of the drug will begin later this year.

Meanwhile, researchers from the Institute for Cellular and Molecular Biology at the University of Texas at Austin have identified a drug target on the flu virus's nonstructural protein, the CP report said. Robert Krug, a researcher at the institute, said the lab has screened molecules that could strike the target and have come up with a good "hit," though development of a drug could take 5 years, even if the work goes smoothly.

An advantage of the nonstructural protein target is that it is the same in different virus strains, unlike other parts of the virus, the story said.

Vietnam to launch trial of H5N1 vaccine
Health officials in Vietnam said the country was set to launch the first human trial of its own H5N1 avian flu vaccine, Agence France-Presse (AFP) reported today.

Nguyen Tran Hien, director of the National Institute of Hygiene and Epidemiology (NIHE) in Hanoi, told AFP the trial will begin as early as July, with the health ministry's approval, and should be finished next year. He said researchers will enroll 20 to 30 volunteers for the study.

Experts from the United States will provide Vietnam with technical assistance to develop the vaccine, US health attaché Michael Iademarco told AFP. The United States provided $1 million to Vabiotech, a company with ties to NIHE, apparently to support the development of the vaccine, Iademarco said.

In the past few weeks, Vietnam has reported five human cases of H5N1 avian flu, with one death, and since early May, bird outbreaks have been reported in 16 of the country's 59 provinces. The World Health Organization has not yet confirmed the recent human cases in Vietnam, so the official case count for now remains at 93 cases and 42 deaths.

See also:

Jun 18 Chugai press release

Mar 21 CIDRAP News story "Japan warns against Tamiflu use in teens"

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