Yourlawyer.com (Tamiflu News)

Relenza Death Linked to Improper Use

Mon, 12 Oct 2009 00:00:00 -0700

The improper use of Relenza Inhalation Powder has been associated with the death of a patient. According to an alert from the U.S. Food & Drug Administration (FDA), the death occurred after Relenza Inhalation Powder was converted to a liquid and administered via mechanical ventilation. Relenza is not intended to be reconstituted in any liquid formulation and is not recommended for use in any nebulizer or mechanical ventilator.

Relenza Inhalation Powder is made by GlaxoSmithKline and is approved for treating adults and children with certain strains of the influenza virus. Relenza is meant to be used with Glaxo’s Diskhaler device. In April, the FDA approved the emergency use of Relenza and another flu drug, Tamiflu, to fight the spread of the H1N1 flu virus.

According to the FDA, Glaxo is aware that Relenza is being removed from its FDA-approved packaging and dissolved in various solutions for the purpose of nebulizing the drug for inhalation by patients who are unable to take oral medications or unable to inhale Relenza using the Diskhaler. Relenza for nebulization has not been approved by the FDA. The safety, effectiveness, and stability of Relenza use by nebulization have not been established.

According to a "Dear Healthcare Provider" letter issued by Glaxo, there has been a report of an influenza patient who died after Relenza was solubilized and administered by mechanical ventilation. The death occurred outside the U.S. and was of a pregnant woman on mechanical ventilation who received Relenza solution via nebulizer for three days. The death was attributed to obstruction of the ventilator. The reporting physician believed that the obstruction in the ventilator was due to stickiness caused by lactose from Relenza in the nebulizing solution, the letter said.

According to a report on Food Consumer, the FDA approved Relenza in July 1999, despite a negative recommendation from its own Anti-viral Drugs Advisory Committee. The committee was "underwhelmed" by the drug's performance and voted 13 to 4 to reject it. The FDA committee members found that Relenza was "no more effective than a placebo in treating common flu symptoms" and that it would "reduce by about one day a patients symptoms," Food Consumer said.

One year after its approval, Glaxo revised the labeling of Relenza to more clearly reflect a risk of serious respiratory adverse events, Food Consumer said.

In March 2008, Glaxo added new warnings to the "Warnings and Precautions" section of the Relenza package insert regarding neuropsychiatric events. In November 2007, an FDA advisory panel had recommended stronger warnings about psychiatric side effects be added to the labeling of both Tamiflu and Relenza. The recommendations where based on a review of nearly 600 psychiatric adverse event reports in Tamiflu patients, and another 115 reports among people taking Relenza.

Tamiflu Dosing Error Warning Issued by FDA

Fri, 25 Sep 2009 00:00:00 -0700

The U.S. Food & Drug Administration (FDA) has issued a Public Health Alert advising pharmacists and pediatrics healthcare professionals about potential dosing errors with Tamiflu (oseltamivir) for Oral Suspension.

The FDA stated that U.S. health care providers typically write prescriptions for liquid medicines in milliliters (mL) or teaspoons, while Tamiflu is dosed in milligrams (mg). The dosing dispenser packaged with Tamiflu has markings only in 30, 45, and 60 mg. The Agency has received reports of errors in which dosing instructions for the patient do not match that of the dosing dispenser.

The FDA is advising health care providers to indicate doses in mg if the dosing dispenser with the drug is in mg. Pharmacists should ensure that the units of measure on the prescription instructions match the dosing device provided with the drug.

In the United States, the FDA approved two antiviral drugs for treatment and prophylaxis of the 2009 H1N1 influenza virus: Tamiflu and Relenza (zanamivir). We recently wrote that medical authorities warned consumers to exercise caution when using these medications, citing the LA Times. Tamiflu and Relenza should be used when necessary and must be used appropriately.

The U.S. Centers for Disease Control and Prevention (CDC) describes the swine flu as a new virus first detected in the U.S. in April 2009 that is spreading from person-to-person worldwide, probably in much the same way that traditional seasonal influenza spreads. Earlier this year, the CDC said that the World Health Organization (WHO) indicated that a pandemic of the new H1N1 flu was underway.

Overuse or misuse of the drugs could pave the way for resistant strains of the emerging swine flu, which could make control of a pandemic all the more problematic, noted the LA Times, previously. Meanwhile, a Tamiflu-resistant strain of Swine Flu has already been reported.

The Public Health Alert, issued by the FDA, can be viewed at: http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm183649.htm

The Dear Healthcare Professional Letter, issued by pharmaceutical maker, Roche, can be viewed at: http://www.fda.gov/downloads/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/UCM183752.pdf

The Information for Pharmacists, issued by the CDC, can be viewed at: http://www.cdc.gov/H1N1flu/pharmacist/pharmacist_info.htm.

Tamiflu-Resistant Swine Flu Emerging

Tue, 30 Jun 2009 00:00:00 -0700

A Tamiflu-resistant strain of Swine Flu—the 2009 H1N1 pandemic virus—has emerged in Denmark. According to Bloomberg.com, Tamiflu drug maker Roche Holding AG said a patient treated with the Tamiflu in Denmark exhibited drug resistance, the first time this has occurred in this outbreak.

Bloomberg.com said the swine flu patient received a low and preventative dose of Tamiflu after coming in contact with someone infected with the virus, said David Reddy, Roche’s influenza task force head. Speaking on a conference call, Reddy said that the patient developed flu symptoms and was diagnosed with a virus mutation that showed resistance to Tamiflu, reported Bloomberg.com.

The Food & Drug Administration (FDA) has approved two antiviral drugs for treatment and prophylaxis of the 2009 H1N1 influenza virus: Tamiflu (oseltamivir phosphate) and Relenza (zanamivir). Tamiflu and Relenza, in addition to their approved labeling, have Emergency Use Authorizations that describe specific permitted uses during this public health emergency.

The BBC explained that Tamiflu is the primary drug being used to fight the swine flu pandemic. Also, according to Reddy, said the BBC, drug resistance was not unexpected, citing that the same can occur with the more common seasonal flu.

Bloomberg.com reported that the patient has recovered and there are no other known cases of the resistant strain, citing Denmark’s National Board of Health. Reddy did point out that according to Tamiflu studies, about 0.4 percent of adults and four percent of children who come down with seasonal influenza develop resistance, “We know from seasonal flu that a proportion of patients can develop resistance,” Reddy said, quoted Bloomberg.com. “We fully expect that this also can occur during treatment with a new flu strain,” Reddy added.

According to Reddy, there are no signs of a Tamiflu-resistant strain of H1N1 circulating, unlike the seasonal H1N1 flu in which Tamiflu-resistant strain emerged in 2009 and is now quite common, said the BBC. The BBC pointed out that experts are concerned that if this were to happen, it could cause Tamiflu to become ineffective.

Britain’s Health Protection Agency said it, "continues to watch for antiviral resistance and will be carrying out regular sample testing throughout this outbreak. We have been monitoring antiviral drug resistance since the beginning of this outbreak," quoted the BBC. The swine flu virus has killed over 300 people worldwide and the World Health Organization (WHO) just announced that 70,893 cases have been reported around the world, said Bloomberg.com.

We recently reported that the FDA released another warning about bogus flu products that are targeting consumers via Websites. The agency stated it is enforcing the laws that protect consumers from illegal products marketed through the Internet that claim to diagnose, prevent, mitigate, treat, or cure the 2009 H1N1 flu virus, but which are not approved, cleared, or authorized by the FDA

Also, in late 2006, the FDA alerted doctors and parents to watch for signs of bizarre behavior in children treated with Tamiflu after federal health officials noticed an increasing number of such cases overseas. There have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu, according to documents posted online at the FDA’s Website. Japan was also the origin of 81 Relenza reports and, according to Health Canada’s adverse reaction database, 27 people reported adverse reactions to Relenza, including one adult who died. One 14-year-old reported nightmares and another six-year-old temporarily lost consciousness. Another 96 people reported adverse reactions to Tamiflu, including 11 adults who died and nine who reported psychiatric problems.

FDA Approves Emergency Use of Tamiflu, Relenza

Tue, 28 Apr 2009 00:00:00 -0700

During the current swine flu outbreak and responding to U.S. Authorizations (EUAs), the U.S. Food and Drug Administration (FDA) is making some diagnostic and treatment tools available, under specific situations, to public health and medical personnel. The FDA issued the EUAs for Relenza (zanamivir) and Tamiflu (oseltamivir phosphate) and the rRT-PCR Swine Flu Panel diagnostic test. The FDA explained the EUA is part of Project BioShield, which became law in July 2004.

The EUA authority permits the FDA to allow use of “unapproved or uncleared medical products or unapproved or uncleared uses of approved or cleared medical products” during an established emergency. Such use ends when either the swine flu emergency is deemed over or the authorization is revoked. Under the EUAs, Tamiflu and Relenza may be given to large population sectors without compliance with label requirements and can be distributed by some public health officials and volunteers based on state and local laws and/or public health emergency responses, explained the FDA.

GlaxoSmithKline’s Relenza can be inhaled to treat influenza in children age seven and older. Roche Laboratories’ Tamiflu is prescribed for children age one and up, and is taken orally within 48 hours of flu symptom onset. Relenza is approved to prevent influenza in adults and children five years of age and older. In a pandemic outbreak, Tamiflu and Relenza would be used to treat people ill with flu, as well as flu prevention and treatment in children under one year. If no flu vaccine is available, Tamiflu could be taken daily for flu prevention. EUAs allow alternate dosing for children older than one.

The FDA determined the EUA for the Swine Flu test may be effective in testing samples from individuals diagnosed with influenza A infections, whose virus subtypes cannot be identified by currently available tests. The EUA allows the Centers for Disease Control and Prevention (CDC) to distribute the test to public health and other qualified laboratories with the needed equipment and trained personnel to perform and interpret results. The test amplifies the viral genetic material from a nasal or nasopharyngeal swab. A positive result indicates presumptive swine flu infection, but not the infections’ stage; a negative result alone does not exclude the possibility of infection.

In November 2007, an FDA advisory panel recommended stronger warnings about psychiatric side effects be added to the labeling of both Tamiflu and Relenza. The recommendations where based on a review of nearly 600 psychiatric adverse event reports in Tamiflu patients, and another 115 reports among people taking Relenza. Documents posted online by FDA staffers at the time said that there have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. Japan was also the origin of 81 of the Relenza reports, but no deaths where associated with that drug. Of the 48 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

In March 2008, the U.S. label of Tamiflu was updated to include new warnings about delirium and abnormal behavior seen in some patients - mostly children - taking the drug. A month later, similar warnings were included on Relenza's label.

Health Canada Probes Relenza Side Effects

Wed, 09 Apr 2008 00:00:00 -0700

Health Canada is looking into reports that Relenza, a drug used to treat the flu, has been linked to deaths and abnormal behavior in children. In November 2007, a US Food & Drug Administration (FDA) advisory panel had recommended stronger warnings about psychiatric side effects be added to the labeling of Relenza and another anti-flu drug, Tamiflu. Those warnings were added to the labeling of Relenza earlier in March, while the Tamiflu label was updated in February.

The FDA advisory panel recommendations where based on a review of nearly 600 psychiatric adverse event reports in Tamiflu patients, and another 115 reports among people taking Relenza. Documents posted online by FDA staffers prior to the meeting said that there have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. Japan was also the origin of 81 of the Relenza reports, but no deaths where associated with that drug. Of the 48 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

Health Canada updated Tamiflu's safety label after reports of bizarre behavior among patients who took the drug last year. The new Canadian investigation into Relenza was sparked by the FDA action. According to Health Canada's adverse reaction database, 27 people have reported adverse reactions to Relenza, including one adult who died. One 14-year-old reported nightmares and another six-year-old temporarily lost consciousness. Another 96 people reported adverse reactions to Tamiflu, including 11 adults who died and nine who reported psychiatric problems.

Canada has stockpiled millions of doses of Tamiflu and Relenza in case of a pandemic flu outbreak. Relenza can be inhaled to treat influenza in children aged seven years and older. Tamiflu is prescribed for children age one and up, and is an oral medicine taken within 48 hours of onset of flu symptoms. In a pandemic outbreak, Tamiflu and Relenza would be used to treat people ill with flu. If there is no flu vaccine available, Tamiflu could also be taken daily to prevent illness.

Relenza Label Updated to Include Psychiatric Side Effect Warnings

Wed, 02 Apr 2008 00:00:00 -0700

Relenza inhalation powder, a drug that lessens symptoms of flu, has had new warnings added to its label about delirium and abnormal behavior seen in patients - mostly children - treated with Relenza, GlaxoSmithKline has announced. In March, the labeling of Tamiflu, a rival flu drug made by Roche Holding AG, was also modified to include similar information.

Relenza was approved by the Food & Drug Administration (FDA) in 1999 to treat flu symptoms. Relenza is indicated for treatment of uncomplicated acute illness due to influenza A and B virus in adults and pediatric patients 7 years of age and older who have been symptomatic for no more than 2 days. Relenza is also approved to help to prevent getting influenza A and B in children and adults age 5 years and older in community and household settings

According to a letter Glaxo sent to healthcare providers dated March 11, the new warnings on neuropsychiatric events have been added to the "Warnings and Precautions" section of the Relenza inhalation powder package insert. The label now says that:

". . .there have been postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury in patients with influenza who were receiving neuraminidase inhibitors, including RELENZA. Because these events were reported voluntarily during clinical practice, estimates of frequency cannot be made, but they appear to be uncommon based on usage data for RELENZA. These events were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The contribution of RELENZA to these events has not been established. Patients with influenza should be closely monitored for signs of abnormal behavior. If neuropsychiatric symptoms occur, the risks and benefits of continuing treatment should be evaluated for each patient."

In addition, the following information has been added to the Relenza Patient Information, in the, "What are important or common possible side effects of taking RELENZA?" section:

"People with influenza (the flu), particularly children and adolescents, may be at an increased risk of seizures, confusion, or abnormal behavior early in their illness. These events may occur after beginning RELENZA or may occur when flu is not treated. These events are uncommon but may result in accidental injury to the patient. Therefore, patients should be observed for signs of unusual behavior and a healthcare professional should be contacted immediately if the patient shows any signs of unusual behavior."

In November 2007, an FDA advisory panel had recommended stronger warnings about psychiatric side effects be added to the labeling of both Tamiflu and Relenza. The recommendations where based on a review of nearly 600 psychiatric adverse event reports in Tamiflu patients, and another 115 reports among people taking Relenza. Documents posted online by FDA staffers at the time said that there have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. Japan was also the origin of 81 of the Relenza reports, but no deaths where associated with that drug. Of the 48 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

Tamiflu Gets New Warnings on Psychiatric Side Effects

Tue, 04 Mar 2008 00:00:00 -0800

Tamiflu prescribing information has been updated to include information about a variety of neurological and behavioral symptoms associated with the drug, the Food & Drug Administration (FDA) announced today. The decision to change the Tamiflu package insert followed the recommendation of an FDA Advisory Panel in November. The FDA Tamiflu advisory panel had reviewed more than 600 cases of Tamiflu psychiatric side effects, including hallucinations and delirium. Many of those Tamiflu side effect reports involved children and some resulted in fatalities.

Tamiflu, manufactured by Roche Laboratories, was approved by the FDA in 1999 for the treatment and prevention of flu in patients 1 year and older. The link between Tamiflu and psychiatric side effects was first reported in Japan. In Japanese patients under sixteen, four adverse events involved fatal falls, and one involved a leukemia patient who developed encephalitis. Also in Japan, there where two reports of deaths in young people aged 17 to 21, one involving a “fatal accident with abnormal behavior” and another encephalitis death. In March 2007, the Japanese Tamiflu adverse event reports prompted that country’s drug regulatory agency to restrict the use of Tamiflu. Of the 48 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

In 2005, the FDA convened an advisory panel to discuss the problems with Tamiflu, but the panel concluded the events likely weren’t related to Tamiflu. However, the panel recommended the agency keep monitoring the drug. On November 13, 2006, the FDA alerted doctors and parents to watch for signs of bizarre behavior in children treated with Tamiflu.

In November 2007, documents posted by FDA staff on the agency's website said that there had been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. That same month, the FDA convened another Tamiflu advisory panel, which recommended stronger warnings on the Tamiflu label regarding the drug's possible neuropsychiatric side effects.

Based on the FDA Advisory Panel's recommendations, the revised "Precautions" section of the Tamiflu package insert will now advise of postmarketing reports (mostly from Japan) of delirium and abnormal behavior leading to injury, and in some cases resulting in fatal outcomes, in patients with influenza who were receiving Tamiflu. The package insert will also warn that these Tamiflu side effects were reported primarily among pediatric patients and often had an abrupt onset and rapid resolution. The label now warns health care providers to monitor influenza patients treated with Tamiflu for signs of abnormal behavior. If such side effects do present, the Tamiflu label says health care providers should weight the risks and benefits of continuing Tamiflu treatment.

Tamiflu Resistant Flu Becoming More Common

Thu, 07 Feb 2008 00:00:00 -0800

Some current influenza viruses are carrying a mutation—A/H1N1-H274Y—that makes them resistant to Tamiflu. The Centers for Disease Control and Prevention (CDC) estimate that a small sampling of flu viruses nationwide carry the mutation. The Tamiflu resistant mutation has occurred in A/H1N1, one of the main circulating strains causing flu this year.

Although Tamiflu is recommended as a treatment when outbreaks occur in health care facilities and to prevent the flu shortly after exposure, vaccination is the preferred and more effective method of prevention. The current vaccine still provides protection against the flu.

Scientists at the World Health Organization (WHO), led by Dr. Frederick Hayden, have discovered evidence of the mutant strain worldwide. Of greatest concern is that resistant viruses have been detected in specimens from people who where never treated with Tamiflu because drug resistance is usually seen in people who have been exposed to a drug.

The percentage of mutant viruses is low—about 3.8 percent in a sampling of 237 specimens from patients nationwide this winter—according to the CDC. Dr. Joseph Bresee, chief of the epidemiology and prevention branch in the CDC's influenza division, feels there is no need to embargo Tamiflu, "This certainly bears close watching," he said yesterday. "We're intensifying our surveillance effort to determine if this is an increasing trend.” Bresee added that, "It was unexpected, mainly because, historically, Tamiflu resistance has been very low. And most resistance we've seen has been among treated people."  Bresee also found it interesting that there is a lack of Tamiflu resistance in Japan, a country where Tamiflu is widely used.

Since last flu season, the CDC enhanced its surveillance in an effort to detect flu viruses resistant to Tamiflu and that increased monitoring has provided the agency with the ability to detect resistant strains quickly, Bresee said. Roche Pharmaceuticals, Tamiflu's maker, noted that some global health experts have cited limitations in the preliminary data, which found resistance to its drug, and have called for further research. Bresee also noted that influenza viruses are constantly mutating through a process called antigenic drift, which causes them to change from one season to the next and, sometimes, within a single flu season. On occasion, these mutations can cause drug resistance, which means the medications either do not work or do not work as well.

Anti-flu drugs belonging to a class called adamantanes were embargoed indefinitely by the CDC in January 2006 because flu viruses developed mutations against the drugs; the medications remain under the embargo. "When we noticed it," Bresee said of the resistance problem, "well over 90 percent of all [influenza A] viruses were resistant.” At the time, the CDC underscored Tamiflu's availability.  Resistance to Tamiflu has been detected by the WHO in Canada and Europe. In a recent sampling, Norway had the highest percentage of viruses carrying the mutation.

The influenza virus is highly active throughout New York State and has grown to high levels in several other states, and—according to surveillance data from the state Health Department—remains high in both Nassau and Suffolk counties.

Tamiflu Resistant Flu Raising Concerns

Tue, 05 Feb 2008 00:00:00 -0800

Tamiflu might not be as effective during a flu pandemic as once thought. Flu strains in the United States, Canada, and parts of Europe are showing a higher resistance to Tamiflu, raising questions about its potential effectiveness in the event of a human bird flu pandemic. The World Health Organization (WHO) reported elevated resistance in North America on Friday, but said it was too early to know the chances for increased Tamiflu resistance in the H5N1 strain of avian influenza. The WHO did not change its recommendation that Tamiflu be used to treat human cases of bird flu.

A number of governments have been stockpiling Tamiflu, which is made by Switzerland's Roche Holding AG and Gilead Sciences Inc. of the U.S. Tamiflu is recommended for use as a first line of defense in case bird flu sparks a human influenza outbreak. Health experts fear that the virus—which now mainly affects poultry—could mutate into a form that spreads easily among people, triggering a deadly pandemic.

The WHO said it was investigating the extent of resistance worldwide to Tamiflu, known generically as oseltamivir, in some seasonal H1N1 flu viruses that have a mutation making them "highly resistant." "The frequency of oseltamivir resistance in H1N1 viruses in the current influenza season is unexpected and the reason why a higher percentage of these viruses are resistant is currently unknown," the WHO said.

The U.S. Centers for Disease Control and Prevention (CDC) reported a five percent prevalence of Tamiflu resistance in H1N1 virus samples tested. In Canada, eight out of 128 samples showed resistance. "These preliminary data indicate that oseltamivir resistance in H1N1 viruses is geographically variable but not limited to Europe," said the WHO in a statement. A preliminary survey issued by the European Centre for Disease Control (ECDC) this week said that of 148 samples of influenza A virus isolated from 10 European countries during November and December, 19 showed Tamiflu resistance; the mutated H1N1 is a sub-type of influenza A. Of 16 samples from Norway, 12 tested positive for Tamiflu resistance.

The new "elevated resistance to oseltamivir" appears limited to seasonal H1N1 viruses and not H3N2 or influenza B, which are circulating, the WHO said. "This means that oseltamivir would most likely be ineffective for treating or preventing infections caused by resistant H1N1 strains, although the drug will be effective against other influenza virus infections," it added. The WHO was contacting national health authorities to determine the extent of drug resistance. Neither Japan—where Tamiflu is widely prescribed for seasonal flu—nor Hong Kong, had seen increased resistance, it said. Past studies found Tamiflu resistance rates ranging from zero to 0.5 percent.

Experts are looking to see if the mutated viruses found early in the winter can compete when regular flu viruses move from one vulnerable respiratory tract to the next. "One of the great conundrums of influenza is the fact that viruses appear and disappear and nobody knows really where they go from or to," said Dr. Maria Zambon, head of the respiratory virus unit of Britain's Health Protection Agency.

Tamiflu Study in Japan Yields Few Answers

Mon, 17 Dec 2007 00:00:00 -0800

A Tamiflu study done in Japan not eased doubts about the flu drug’s safety and possible side effects. Over half of all influenza patients in Japan exhibiting abnormal behaviors had taken the drug Tamiflu; however, it is still not clear if there was a causal link between the drug Tamiflu and their actions, a government report showed on Monday. Japan is investigating whether there is any link between Tamiflu, made by Roche Holding AG, and neuropsychiatric problems after more than 100 people, mostly young people, exhibited erratic behaviors after taking the drug, such as jumping from buildings. There have been a total of eight cases of death after abnormal or possibly abnormal behavior. The Health Ministry report indicated that of the 137 patients who had shown abnormal behavior, 82 had taken Tamiflu, while 52 had not. In the US, the Food & Drug Administration is considering

But the report, compiled by a group of doctors and other health experts, explained that their figures were difficult to assess because it was not clear what percentage of all influenza patients had been prescribed Tamiflu. The report also said that the number of patients showing abnormal behavior did not drop following the government’s warning in March against prescribing Tamiflu to those aged 10 to 19.

A Health Ministry official said that the study had been inconclusive but that a separate group of doctors and experts would present their own study later in the month, saying that they hope to reach some kind of conclusion at that time.

Tamiflu is taken for the treatment of regular seasonal influenza symptoms and is recognized as one of the best defenses against possible bird flu pandemic. According to recent research, Tamiflu successfully suppress the avian flu virus, which public health experts say threatens to cause a world flu pandemic. The tests, which were conducted on 80 mice, demonstrated that Tamiflu could kill the newest strain of the H4N1 virus that infected poultry in Vietnam, Cambodia, and China. Researchers reported a 50%-80% survival rate in mice administered high doses of the drug 5.

Conversely, public health officials do not paint a promising picture, saying that if the avian flu were to begin spreading rapidly among humans, they would need to know whether the antiviral drugs could prevent and treat the avian flu, because in the early stages of a global outbreak most people would be unvaccinated. Officials claim it would take months to manufacture and distribute the medication. Experts also fear the new, ever-morphing strains of the virus are more dangerous than the 1997 version that killed six people in Hong Kong. The disease has killed over 50 people in Asia. In an effort to prepare for a pandemic, governments are stockpiling Tamiflu.

Roche and its Japanese partner Chugai Pharmaceutical Co. Ltd. have said that no causal relationship has been established between Tamiflu and the neuropsychiatric symptoms. They argued that doctors say influenza itself can cause abnormal behavior.

Tamiflu, known generically as oseltamivir, is widely prescribed in Japan. Chugai estimates some 35 million people have taken the drug, accounting for around 70 percent of the world's Tamiflu consumption.

Tamiflu and Relenza Need Stronger Warnings, FDA Panel Says

Wed, 28 Nov 2007 00:00:00 -0800

Tamiflu and Relenza, drugs used to treat the flu, should bear warnings about possible psychiatric side effects, a Food & Drug Association (FDA) panel said yesterday. The recommendation came in the wake of a number of reports that both Tamiflu and Relenza had been linked to episodes of abnormal behavior that included delirium and hallucinations. Many of the reports involved children treated with Tamiflu or Relenza, and some where fatal.

The FDA advisory panel recommendations where based on a review of nearly 600 psychiatric adverse event reports in Tamiflu patients, and another 115 reports among people taking Relenza. Documents posted online by FDA staffers last week said that there have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. Japan was also the origin of 81 of the Relenza reports, but no deaths where associated with that drug. Of the 48 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

Although no direct link with the antiviral drugs has been established, the advisory panel recommended adding the new case reports to the Relenza and Tamiflu labels. It was noted that some of the abnormal behavior was seen in flu patients who did not take the drugs, suggesting a possible link to the disease itself. While some panel members did favor mentioning the fatalities associated with Tamiflu on a new label, a formal vote on that issue was not taken. The panel voted to generally note the newly reported cases of neuropsychiatric behavior seen with Relenza.

Officials from GlaxoSmithKline, the maker of Relenza, and Tamiflu manufacturer Roche AG said they opposed label changes and cited data showing no causal link between the drugs and adverse events. It is "very difficult to differentiate drug from disease," Dr. Jonathan Solsky of Roche told the panel.

One panel member who favored stronger warnings on Tamiflu and Relenza said that the benefits of the drugs where not enough to warrant the psychiatric risks associated, even though they are rare events. In most cases, Tamiflu or Relenza will only shorten the duration of the flu by about one day.

The flu virus is a major cause of death and illness in the United States. Complications from the illness kill about 36,000 Americans a year, a government expert told the panel. Children and the elderly are especially at risk.

The FDA is under no obligation to follow the recommendations of the advisory panel, although in most cases is does so.

Tamiflu Linked to 'Abnormal Behavior' in Children, Label Changes Sought

Mon, 26 Nov 2007 00:00:00 -0800

Tamiflu, a drug used to treat the flu, has been linked to abnormal behavior and other brain side effects in more than 50 children in the United States, and tomorrow a Food & Drug Administration (FDA) advisory panel will meet to discuss what should be done about these dangerous Tamiflu side effects. Last Friday, a report prepared by FDA staffers recommended that new warnings be placed on the label of Tamiflu regarding such side effects. The FDA report also recommended new warnings for Relenza, another anti-flu drug.

Since Tamiflu was introduced in 1999, the FDA has received 55 adverse event reports involving children. Twenty-two of the Tamiflu side effects reports where considered "serious" and involved convulsions, delirium or delusions. Documents posted online last week by FDA staffers for tomorrow's advisory panel meeting recommended new psychiatric warnings for Tamiflu and Relenza. Though Tamiflu already bears a psychiatric event warning, FDA staffers have recommended that it should be strengthened to say: "In some cases, these behaviors resulted in serious injury, including death, in adults and pediatric patients." The recommendations also say that the Relenza label should be changed to warn of "reports of hallucinations, delirium and abnormal behavior" observed in some patients taking the drug.

The link between Tamiflu and psychiatric side effects was first reported in Japan. While none of the adverse Tamiflu events reported in the US involved fatalities, several in Japan resulted in deaths. In patients under sixteen, four adverse events involved fatal falls, and one involved a leukemia patient who developed encephalitis. Also in Japan, there where two reports of deaths in young people aged 17 to 21, one involving a "fatal accident with abnormal behavior" and another encephalitis death. In March, the Japanese Tamiflu adverse event reports prompted that country's drug regulatory agency to restrict the use of Tamiflu. Japan also announced that it would be reviewing the safety of Relenza and another anti-flu drug, Amantadine, after those drugs were also linked to psychiatric events. Japan has been a major market for Tamiflu, and 75% of all Tamiflu prescriptions where written there.

In 2005, the FDA convened an advisory panel to discuss the problems with Tamiflu, but the panel concluded the events likely weren't related to Tamiflu. However, the panel recommended the agency keep monitoring the drug. On November 13, 2006, the FDA alerted doctors and parents to watch for signs of bizarre behavior in children treated with Tamiflu. At that time, The FDA updated the label after receiving the 103 reports of abnormal behavior, most of which involved children in Japan.

Those reports also led the FDA to monitor Amantadine, but so far staffers are not recommending any label changes. Amantadine already has a strong warning regarding seizures and suicide attempts seen in users.

Tamiflu, Relenza Flu Drugs Could Soon Get Warnings for Hallucinations, Delirium, Other Psychiatric Problems

Fri, 23 Nov 2007 00:00:00 -0800

Tamiflu and Relenza, drugs used to treat the flu, could soon bear new warnings about psychiatric side effects if the recommendations of Food & Drug Administration (FDA) staffers are followed. According to documents released today, FDA staffers have recommended the new warnings because of reports linking Tamiflu and Relenza to psychiatric events, including hallucinations, delirium and other abnormal behavior. An FDA advisory panel is set to review Tamiflu and Relenza safety at a meeting next week.

Documents prepared for next week’s FDA advisory panel meeting where posted on the agency’s website today. In those documents, FDA staff have recommended new psychiatric warnings for Tamiflu and Relenza. The recommendation says that the Relenza label should be changed to warn of “reports of hallucinations, delirium and abnormal behavior” observed in some patients taking the drug. Though Tamiflu already bears a psychiatric event warning, FDA staffers say it should be strengthened to say: “In some cases, these behaviors resulted in serious injury, including death, in adults and pediatric patients.” The recommendations included in the online documents will be presented to an FDA advisory panel on Tuesday, November 27.

The FDA staff recommendations where based on a review of nearly 600 psychiatric event reports in Tamiflu patients, and another 115 reports among people taking Relenza. The online documents said that there have been reports of 596 neuropsychiatric events, including 16 neuropsychiatric-related deaths, among children and adults taking Tamiflu. Among those reports, 75% came from Japan. In total, the FDA said, there were 25 deaths from all causes reported among Tamiflu users on a world-wide basis in patients younger than 21. Japan was also the origin of 81 of the Relenza reports, but no deaths where associated with that drug. Of the 50 million people treated with Tamiflu since its approval in 1999, the majority of users – 35 million – have been in Japan.

In 2005, Japan issued a Tamiflu warning against prescribing the drug to people between the ages of 10 and 19. The Japanese Tamiflu warning came after 100 people, mostly young, experienced a psychiatric event after taking Tamiflu. The FDA convened an advisory panel to discuss the matter that year, and the FDA and the panel concluded the events likely weren't related to Tamiflu. However, the panel recommended the agency keep monitoring the drug. Earlier this year, Japan also announced that it would be reviewing the safety of Relenza and another anti-flu drug, Amantadine, after those drugs were also linked to psychiatric events.

Those reports also led the FDA to monitor Amantadine, but so far staffers are not recommending any label changes. Amantadine already has a strong warning regarding seizures and suicide attempts seen in users.

Health Canada Issues New Warning Regarding Tamiflu

Wed, 29 Nov 2006 00:00:00 -0800

The popular antiviral drug Tamiflu is under fire again, this time from Health Canada. The Canadian government issued a new safety advisory today, warning consumers that Tamiflu may be linked to hallucinations and abnormal behavior, including self harm. In conjunction with the new warning, Health Canada is asking manufacturer Hoffmann-La Roche to update its prescription information to reflect these risks.

Health Canada was spurred to action by reports coming from overseas, primarily Japan, of teenagers and children who have suffered adverse psychiatric effects while taking Tamiflu. According to Health Canada, as of November 11 “there have been 84 reports of adverse events occurring in Canadian patients using Tamiflu, including 10 which reported a fatal outcome. A causal relationship has not been confirmed in these cases. There have been seven Canadian reports of psychiatric adverse events, suspected by those reporting the events, due to Tamiflu, most involving elderly patients. There have been no Canadian reports of abnormal behavior or deaths involving children.”

So far, there has been no definitive connection made between these adverse effects and the drug. It’s possible that the high fever and other complications associated with influenza may be responsible for some of the reported abnormal behaviors.

The U.S Food and Drug Administration (FDA) issued a similar report earlier this month. According to the FDA, there were more than 100 reports of abnormal behavior including delirium and suicidal tendencies--in Tamiflu patients between August of 2005 and July of this year. The FDA is considering adding new warnings to the Tamiflu label in order to inform patients of the risks involved.

Health Canada issues warning about Tamiflu drug

Wed, 29 Nov 2006 00:00:00 -0800

Health Canada is asking the manufacturers of Tamiflu to warn consumers of hallucinations and abnormal behaviour, including self harm, as possible side effects.

Manufacturer Hoffmann-La Roche Limited received a similar request from the U.S. Food and Drug Administration last month.

While no direct connection has been established, the caution comes as a result of children and teenagers, primarily from Japan, experiencing such behaviour.

Dr. Colin Lee, co-author of "The Flu Pandemic and You", explained to CTV.ca on Wednesday the reason behind the notice.

"The warning comes from Japan where they certainly use more Tamiflu than we do in North America about 10 times more," said Lee. "Just like any other medication or drug there is a surveillance system to look for possible side effects."

Lee said the higher rate of use in Japan most likely accounts for the higher reports of adverse reactions.

"We don't use it very much in general and in children (in Canada) so we may not see it; therefore, it is prudent to look for this possibility," said Lee.

However, he said no definitive connection has been made between the behaviour and the drug.

"They have noted that there may have been an association with about 100 new cases of bizarre behaviour of people who were taking it," said Lee. "They're not sure if it was from the flu itself, but one of the possibilities is an association with taking Tamiflu and these were in children."

Lee said parents should consult with a physician before giving the medication to children.

"Children are not just small adults, the way they metabolize medication so it's not unusual to see medication that has some side effects in children and not in adults," said Lee.

Other than consulting with a physician, Lee said supervising children on the medication should be enough of a precaution.

"They are having no reports of cases in Canada with such side effects, there is no definite causal link between the medication and these side effects in children," said Lee.

As of November 11, 2006, there have been 84 reports of adverse events occurring in Canadian patients using Tamiflu, 10 which have proven fatal. A causal relationship has not been confirmed in these cases which did not involve abnormal behaviour or child deaths.

Tamiflu works if taken within 48 hours of getting flu-type symptoms. On average it reduces the length of the sickness by one day. Also, Tamiflu can be used to prevent infection in cases of an outbreak when taken before getting sick.

The drug is different from the flu shot vaccine which has a 70 to 90 per cent effectiveness rate of prevention.

FDA panel to review safety of 16 drugs in children

Wed, 15 Nov 2006 00:00:00 -0800

A Food and Drug Administration panel is set to meet Thursday to discuss the safety review of 16 drugs, including flu drug Tamiflu, in pediatric patients.

The pediatric advisory committee will evaluate new and updated reports by the FDA staff that include information on the drugs' safety compiled over a year. The panel will then make recommendations that could include label changes or further investigation of adverse events.

The FDA isn't required to follow the panel's suggestions, but it usually does.

Although the panel was to issue an opinion on Tamiflu's label Thursday, on Tuesday its manufacturer, Roche Holding AG (RHHBY), said it would follow the FDA staff's recommendation in the report and update the label to warn patients of potential abnormal behavior during treatment, including delirium and hallucinations.

In its report, the staff said the label should be changed following a review that found 103 cases of "neuropsychiatric adverse events," including the death of a 14-year-old boy who fell after climbing on his condominium balcony's railing.

According to documents posted on the FDA Web site ahead of Thursday's meeting, eight drugs under review didn't raise any safety concerns. They include cholesterol-lowering medications Lipitor from Pfizer Inc. (PFE) and Zocor from Merck & Co. (MRK), Eli Lilly & Co.'s (LLY) cancer drug Gemzar, and Johnson & Johnson's (JNJ) Ditropan to treat bladder instability.

The other eight drugs either presented new unlabeled safety concerns or "other attributes," including labeled but "serious adverse events of interest" and past safety concerns, the FDA said.

Included in this group are Pfizer's Zyvox, GlaxoSmithKline PLC's (GSK) Zofran and Avandia, Forest Laboratories Inc.'s (FRX) Celexa, Novartis AG's (NVS) Trileptal, Wyeth's (WYE) Rapamune and Abbott Laboratories' (ABT) Norvir.

In an updated report for depression drug Celexa, the FDA staff identified three new cases associated with QT prolongation, which can cause a fatal arrhythmia, since August 2003. The FDA requested the review following a prior report that found a possible association between the drug and the problem in all ages.

"However, this updated review of three new cases didn't find any well-documented cases of QT prolongation associated with using regular doses of (Celexa) in pediatric patients," the FDA staff concluded.

On Pfizer's Zyvox, which is indicated for treatment of certain bacterial infections, the FDA staff found six unlabeled events of "cardiac nature" during the one-year review. The report, however, said the cases "cannot be definitively associated" with the drug.

In the report on epilepsy drug Trileptal, the FDA staff recorded 84 adverse events in children taking the drug in the year-long review. Those events included one death, 52 unlabeled and 31 labeled cases. The staff said the unlabeled cases were too few to "characterize any one adverse event as a potential safety signal."

On Wyeth's Rapamune, the investigation found 19 pediatric cases of adverse events, including two reports of fluid collection that develops between the lining of the heart and the heart itself, and one report of cerebral bleeding.
Rapamune is indicated for the prophylaxis of organ rejection in patients ages 13 or older receiving a renal transplant. The FDA staff, however, said the majority of children it studied were under 12 years of age.

The report found it was "premature" to determine if the drug "played a clear role" in the adverse events reported.
On Glaxo's Zofran, used to prevent nausea and vomiting associated with chemotherapy and radiotherapy for cancer, the FDA staff identified 20 adverse events over a year, including one death. The report said, however, that most patients had underlying conditions or were taking other medication, making it difficult to link the events to the use of Zofran.
In the review of diabetes drug Avandia, the staff found two adverse cases during the one-year period, one involving accidental ingestion and the other involving behavioral changes. It said there were too few reported events to draw any safety conclusion.

On Abbott Labs' Norvir, used to treat HIV patients, the review found 33 adverse events in children in a period of one year, including skin reactions, anemia and pancreatitis. There were three deaths, none directly related to the use of the drug, the FDA said, adding it didn't find any safety concerns.

In the reports, the staff said it will continue to monitor adverse events related to the drugs. The FDA panel will meet at the agency's headquarters in Rockville, Md.

FDA: Tamiflu patients need monitoring

Tue, 14 Nov 2006 00:00:00 -0800

More than 100 recent cases of delirium, hallucinations and other unusual psychiatric behavior in Japanese patients treated with Tamiflu should have parents watching for similar reactions when treating their children with the flu drug.

That's the new advice from the Food and Drug Administration in adding a new precaution to the label of the influenza drug, prescribed about 2 million times a year in the United States.

The FDA updated the label after receiving the 103 reports of abnormal behavior, most of which involved children in Japan. Japan uses more Tamiflu than any other country in the world, with more than 30 million prescriptions since 2001. It's been prescribed about 8 million times in the U.S. since 1999.

The FDA said a relationship between the drug and the behavior had not been established and that the updated label was "intended to mitigate a potential risk associated with Tamiflu." It recommends that close monitoring of patients begin immediately after starting treatment with the drug.

The changes bring the U.S. label more in line with the Japanese one, which already warned that such abnormal behavior could occur. The previous FDA-approved label mentioned only that "seizure and confusion" had been seen in some patients.

Tamiflu is made by the Swiss pharmaceutical company Roche Holding AG. Roche spokesman Terence Hurley said there was no evidence the drug caused the rarely occurring adverse events.

Both Roche and the FDA also said that severe cases of the flu can spark the abnormal behavior flagged in the updated label.

Furthermore, the FDA acknowledged that stopping treatment with Tamiflu could actually harm influenza patients if the virus is the cause of delirium, hallucinations and other abnormal behavior, such as aggression and suicidal thoughts.

Health officials have been sensitive about taking any action that might dissuade people from taking Tamiflu, since the drug could play an important role in an outbreak of bird flu. The drug doesn't prevent flu but can reduce the length and severity of its symptoms.

Previously, Roche has cited studies from the United States and Canada that show the death rate of influenza patients who took Tamiflu was far below those who did not.

Still, the number of reports of bizarre behavior is increasing.

The 103 new cases occurred between Aug. 29, 2005, and July 6, 2006. The tally marks a sharp increase when compared with the 126 similar cases logged over more than five years between the drug's approval in 1999 and August 2005, the FDA said.

Even though severe cases of the flu can spark abnormal behavior, the number and nature of the newly reported cases along with comments from doctors who believe the behavior was associated with the drug keep the FDA from ruling out Tamiflu as the cause, the agency said.

Tamiflu is one of the few drugs believed effective in treating bird flu, which health officials fear could spark a pandemic should it mutate into a form easily passed from human to human.

According to the label, Tamiflu is for the treatment of uncomplicated acute illness due to flu in patients 1 year and older who have shown symptoms for no more than two days.

Flu drug carries new warning after delirium reports

Tue, 14 Nov 2006 00:00:00 -0800

The drug Tamiflu now carries a new warning following reports of delirium among some people, mostly in Japan, taking the medication to treat influenza, the manufacturer and US regulators announced.

The notification to doctors from the US Food and Drug Administration (FDA), which regulates medicine, and the Swiss pharmaceuticals giant Roche, which manufactures Tamiflu, also used to fight the deadly strain of bird flu, was reported on the FDA website Monday.

The antiviral drug's "precautions section" notes that "there have been postmarketing reports (mostly from Japan) of self-injury and delirium with the use of Tamiflu in patients with influenza," according to a copy posted on the FDA site.

"The reports were primarily among pediatric patients. The relative contribution of the drug to these events is not known," the text says.

"Patients with influenza should be closely monitored for signs of abnormal behavior throughout the treatment period," it adds.

There have been 103 cases, 95 of them in Japan, of delirium among people with the flu who took Tamiflu, especially among children and adolescents, the FDA said, adding that 60 percent of the patients were under 17. Suicide was reported in some cases.

The "possible side effects" section of the drug's "patient information" insert now notes: "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."

Roche said that nothing indicated that the drug was responsible for the neuropsychiatric problems.

Millions of doses of Tamiflu are being stockpiled by governments and the World Health Organization in the event of a global flu pandemic, which could be sparked if the H5N1 virus, at present transmissible from birds to humans, mutates into a form easily contagious among humans.

Tamiflu linked to abnormal behavior

Tue, 14 Nov 2006 00:00:00 -0800

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.

FDA staff calls for Tamiflu to carry behavior warning

Mon, 13 Nov 2006 00:00:00 -0800

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

The staff's recommendation, posted on the FDA's Web site Monday, 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 his condominium balcony railing.

From the 103 cases, 67% are pediatric patients and 95% occurred outside the U.S., mostly in Japan.

Two other related deaths by people who took Tamiflu were reported, including an adult who left a suicide note. There have been other reports of people who had jumped or fallen, but they survived the injuries, the FDA staff said.

The officials still don't know if the new cases, reported from August 2005 to July this year, are linked to the drug, to the flu virus, or both.

The staff's recommendation on label changes is to be discussed Thursday by FDA's pediatric advisory committee. Although the agency isn't required to follow the panel's suggestions, it usually does.

Last year, both the committee and the panel said Tamiflu was safe for use in children and said there was no link to reports of 12 deaths in children taking the drug in Japan.

A previous review by the FDA staff covering 1999 to August 2005 found 126 cases of neuropsychiatric adverse events from people who took Tamiflu.

In Japan, Tamiflu's label already carries information on such events, and the FDA staff said "it would be prudent to update the U.S. labeling to be similar in scope."

"In particular, we want to alert the clinician, patient and patient's guardian to closely monitor the patient in order to abort any attempt at unsafe behavior," the staff said in a 23-page report.

FDA urges new Tamiflu warning

Mon, 13 Nov 2006 00:00:00 -0800

The U.S. Food and Drug Administration Monday urged adding a new warning for the flu drug Tamiflu amid reports of psychiatric problems in patients who take it.

"It is still unclear whether these neuropsychiatric events are drug-related only, disease manifestation alone, or a combination of drug-disease expression," said an FDA staff summary posted on the agency's Web site.

The FDA reviewers said they evaluated 103 reports of hallucinations, suicidal behavior and other mental problems mostly among children from August 2005 to July 2006. Three deaths were from falls.

Nearly all the cases, 95 out of 103, came from Japan, the FDA staff said.

Tamiflu was prescribed 24.5 million times in Japan between 2001 and 2005, compared with 6.5 million times in the United States, which has more than twice the population, the FDA Web site said.

Tamiflu is made by the Swiss pharmaceutical company Roche Holding AG, which has discussed label changes with the FDA, a company spokesman said.

Tamiflu may get 'abnormal behavior' label

Mon, 13 Nov 2006 00:00:00 -0800

Doctors and parents should watch for signs of bizarre behavior in children treated with the flu drug Tamiflu, federal health officials suggested Monday in citing an increasing number of such cases from overseas.

Food and Drug Administration officials still don't know if the more than 100 new cases, including three deaths from falls, are linked to the drug or to the flu virus - or a combination of both. Most of the reported cases involved children.

Still, FDA staff suggested updating Tamiflu's label to recommend that all patients, especially children, be closely monitored while on the drug. They also acknowledged that stopping treatment with Tamiflu could actually harm influenza patients if the virus is the cause of delirium, hallucinations and other abnormal behavior, such as aggression and suicidal thoughts.

The FDA's pediatric advisory committee is to discuss the recommendation Thursday. The FDA isn't required to follow the advice of its outside panels but usually does. An FDA spokeswoman did not immediately return a call seeking comment.

The meeting comes a year after the same panel of outside experts rejected linking Tamiflu to reports of 12 deaths in Japanese children since 2000 and voted against changing the drug's label to suggest any such concern. At that time, however, the committee did recommend that the FDA continue to monitor the drug's safety and return a year later with an update.

The panel's decision after reviewing the new update is likely to be closely watched, since Tamiflu could play an important role in an outbreak of bird flu. The drug doesn't prevent flu but can reduce the length and severity of its symptoms.

Most of the 103 new cases of bizarre behavior are from Japan, where the number of Tamiflu prescriptions is about 10 times that in the United States, with more than twice the population.

The new cases occurred during a 10-month period, between Aug. 29, 2005, and July 6, 2006. The tally marks a sharp increase to the 126 similar cases logged over the more than five years between the drug's approval in 1999 and August 2005, the FDA said.

The Japanese Tamiflu label now warns that disturbances in consciousness, abnormal behavior, delirium, hallucination, delusion and convulsion may occur. It also recommends patients be carefully monitored and the drug stopped if any abnormality is observed.

Even though severe cases of the flu can spark those conditions, the number and nature of the cases - along with comments from doctors who believe the abnormal behavior was associated with the drug keep the FDA from ruling out Tamiflu as the cause, according to agency documents.

For that reason, the proposed changes would bring the U.S. label more in line with the Japanese one, and warn of abnormal behavior and recommend that patients, especially children, be closely monitored. However, the proposed U.S. version would recommend treatment be stopped only on a doctor's advice.

FDA staff called the proposed changes "prudent," since U.S. Tamiflu use could jump to Japanese levels. The current U.S. label mentions only "seizure and confusion" seen in some patients.

Tamiflu is made by the Swiss pharmaceutical company Roche Holding AG. A Roche spokesman did not immediately return messages seeking comment. Previously, Roche has cited studies from the United States and Canada that show the death incidence rate of influenza patients who took Tamiflu was far below those who did not.

Tamiflu is one of the few drugs believed effective in treating bird flu, which health officials fear could spark a pandemic should it mutate into a form easily passed from human to human.

Tamiflu Child Abnormal Behavior Death Injury Lawyer

Mon, 13 Nov 2006 00:00:00 -0800

Injured by Tamiflu

On November 13, 2006, the FDA alerted doctors and parents too watch for signs of bizarre behavior in children treated with Tamiflu. This warning was based upon federal health officials noticing an increasing number of such cases from overseas. Tamiflu (generic: oseltamivir phosphate) is prescribed to treat the flu is manufactured by Roche Laboratories, Inc. and was approved for use by the FDA on October 27, 1999.

Food and Drug Administration (FDA) representatives to date still don't know if the more than 100 new cases, which include three deaths from falls, are associated to the drug or to the flu virus or a combination of both. The majority of the reported cases include children. FDA officials have suggested and are meeting on November 16, 2006 to discuss updating Tamiflu's label to recommend that all patients, particularly children, be closely monitored while on the drug. The FDA also acknowledged that stopping treatment with Tamiflu could actually harm influenza patients if the virus is the cause of delirium, hallucinations and other abnormal behavior, such as aggression and suicidal thoughts.

The new meeting comes one year after the same panel of outside experts rejected linking Tamiflu to reports of 12 deaths in Japanese children since 2000 and voted against changing the drug's label to suggest any such concern. At that point in time, the committee did recommend that the FDA continue to monitor the drug's safety and return a year later with an update. Nearly all of the 103 new cases of bizarre behavior are from Japan, where the number of Tamiflu prescriptions is about 10 times that in the United States, with more than twice the population.

The latest cases occurred during a 10-month period, between Aug. 29, 2005, and July 6, 2006. The tally marks a sharp increase to the 126 similar cases logged over the more than five years between the drug's approval in 1999 and August 2005, the FDA said. The Japanese Tamiflu label now warns that disturbances in consciousness, abnormal behavior, delirium, hallucination, delusion and convulsion may occur. It also recommends patients be carefully monitored and the drug stopped if any abnormality is observed.

The FDA calls the proposed changes "prudent," since U.S. Tamiflu use could jump to Japanese levels. The current U.S. label mentions only "seizure and confusion" seen in some patients.

If your child has been prescribed Tamiflu and experienced abnormal behavior that resulted in death, please fill out the form to the right for a free case evaluation by one of our defective drug attorneys.