Roche Release: Earlier Initiation of Tamiflu(R) Treatment Improves Clinical Benefits for Children With Influenza
TORONTO, June 22 /PRNewswire/ -- A new retrospective analysis of a pivotal pediatric study indicates that earlier initiation of treatment with Tamiflu(R) (oseltamivir phosphate) is associated with greater reduction in illness duration, symptom severity and secondary complications in children with influenza.(1) According to the data, treatment initiated within 24 hours of symptom onset provides clinically meaningful improvements, compared with treatment initiated within 24 - 48 hours. Tamiflu, the leading prescription antiviral flu medication, is indicated for the prevention and treatment of influenza types A and B in patients one year and older.
Researchers at Roche, which makes Tamiflu, collaborated with researchers at the University of Alabama (Birmingham) and Primary Physicians Research in Pittsburgh to conduct additional analysis of data from an earlier study, "Oral Oseltamivir Treatment in Children," to explore the impact of time-to-treatment initiation. The new findings were presented today at the Options for the Control of Influenza VI conference in Toronto during the "Clinical Guidance and Policies" workshop.
"Children bear a disproportionately high burden of influenza and are at particular risk of flu-related complications," said Regina Dutkowski, PhD, Clinical Director at Roche, who presented the data. "There is a crucial 48 hour window of opportunity to initiate antiviral therapy, and this analysis further underscores the importance of treating influenza in children at the first sign of symptoms."
Key Findings
The analysis showed that early initiation of treatment (within 24 hours of symptom onset) was associated with more marked treatment effects when compared with later initiation (24 - 48 hours) for several parameters. Children treated with Tamiflu within 24 hours of symptom onset had a 34.5 percent reduction in duration of illness versus placebo, compared to a 19.3 percent reduction over placebo in the group treated later. Children treated within 24 hours also showed a more pronounced reduction of fever duration versus placebo and were 54.2 percent less likely to develop otitis media (ear infection).
While the beneficial effects of Tamiflu treatment over placebo were observed in all analyses, the impact on time to return to normal health (34.2 percent in the <24 hours group vs. 37.8 percent in the 'greater than or equal to' 24 hours group) and the overall incidence of influenza-associated complications (37.9 percent in the <24 hours group vs. 40.7 percent in the 'greater than or equal to' 24 hours group) was less clear. The table below provides a summary of outcomes:
Early treatment initiation Later treatment initiation (<24 hours) (within 24-48 hours) Oseltamivir- Placebo Reduction Oseltamivir- Placebo Reduction treatment (n=89) treatment (n=146) (n=82) (n=135) Time to 1.98 1.10 freedom 3.75 5.73 days, or 4.61 5.71 days or from illness days days 34.5% days days 19.3% Duration of 1.81 3.10 1.29 1.8 2.7 0.90 fever days days days, or days days days, or 41.5% 33.1% Symptom score 827.3 1739.3 52.4% 1040.1 1245.3 16.5% Time to 3.15 4.78 1.63 2.79 4.49 1.70 return to days days days, or days days days, or normal health 34.2% 37.8% Incidence of secondary complications 18% 29% 37.9% 16% 27% 40.7% Incidence of otitis media 11% 24% 54.2% 13% 20% 35%
Study Design
A total of 695 children (one to 12 years of age), 452 of whom were influenza infected, were randomized into the original double-blind, placebo- controlled study, which was previously published in the Pediatric Infectious Disease Journal.(2) The study was conducted at sites in the U.S. (70 sites) and Canada (10 sites) during the 1998-1999 influenza season. Inclusion was based on fever greater than or equal to 38 degrees Celsius and cough or coryza (nasal congestion) of < 48 hours in duration. Participants received either Tamiflu liquid suspension (2 mg/kg/dose, n=217) or placebo (n=235) twice daily for five days.
The study endpoints were time to freedom from illness; duration of fever; symptom duration and severity; time to return to normal health and activity; and the incidence of secondary complications including bronchitis, pneumonia, sinusitis and otitis media. The symptom score was assessed using the validated Canadian Acute Respiratory Infection and Flu Scale (CARIFS).
Flu's Impact on Children
Influenza is a serious illness that affects up to 40 million Americans every year, leading to approximately 200,000 hospitalizations and 36,000 deaths.(3) Research indicates that children are especially vulnerable to influenza and its complications. On average, one in three children in the U.S. is affected by influenza annually.(4) Children are also two to three times more likely than adults to get sick with the flu, according to the National Institute for Allergies and Infectious Diseases (NIAID).(5)
Additionally, children represent one of the most important links in influenza transmission.(6) Experts believe that compared with adults, children do not have as much natural immunity to influenza because they have had less lifetime exposure. Close contact with each other in school, home and daycare settings increases children's risk of getting and spreading the virus.
Role of Antiviral Medications
Prescription antiviral medications like Tamiflu are an important complement to vaccines in the prevention of seasonal influenza. In addition, antiviral medications play a unique role in the treatment of influenza by reducing the duration of illness.
Tamiflu belongs to a class of antiviral medicines called neuraminidase inhibitors (NAI), which help prevent the flu virus from spreading inside the body. Virtually all common flu viruses have the neuraminidase protein on their surface, which enables them to migrate from cell to cell, replicating and spreading throughout the body. Inhibiting the neuraminidase activity is believed to interfere with this process, possibly causing the viruses to become trapped and die out. Tamiflu is given orally and is systemically absorbed, meaning that it can reach all key sites in the body where the virus multiplies.
When taken within 48 hours of symptom onset, research shows Tamiflu can reduce duration of illness by 1.3 days. Clinical trials also indicate that Tamiflu is up to 89 percent effective in preventing flu when taken within 48 hours of exposure.
About Tamiflu
Tamiflu, co-developed by Gilead Sciences, Inc., based in Foster City, CA, is a systemic treatment for the most common strains of influenza (types A and B). Tamiflu is indicated for the treatment of uncomplicated influenza caused by viruses types A and B in patients one year and older who have had flu symptoms for no more than two days. Tamiflu is also indicated for the prevention of influenza in patients one year and older. Tamiflu is not a substitute for annual early vaccination as recommended by the Centers for Disease Control and Prevention.
Tamiflu has not been shown to be effective against any illness other than that caused by influenza types A and B. Efficacy of treatment in patients with chronic cardiac and/or respiratory disease has not been established. No difference in the incidence of complications was seen between the treatment and placebo groups in this population. No information is available regarding treatment of influenza in patients at imminent risk of requiring hospitalization. Efficacy of Tamiflu has not been established in immunocompromised patients.
Safety and efficacy of repeated treatment or prophylaxis courses have not been studied. In post-marketing experience, rare cases of anaphylaxis and serious skin reactions, including toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiforme, have been reported.
There have been postmarketing reports (mostly from Japan) of self-injury and delirium with the use of Tamiflu in patients with influenza. The reports were primarily among children. The relative contribution of the drug to these events is not known. Patients with influenza should be closely monitored for signs of abnormal behavior throughout the treatment period.
In treatment studies in adult patients, the most frequently reported adverse events (incidence greater than or equal to 1%) were nausea and vomiting. Other events reported numerically more frequently in patients taking Tamiflu compared with placebo were bronchitis, insomnia and vertigo. In treatment studies in patients one to 12 years old, the most frequently reported adverse event (incidence greater than or equal to 1%) was vomiting (15%). Other events reported more frequently in patients taking Tamiflu compared with placebo included abdominal pain (5% vs. 4%), nosebleed (3% vs. 3%), ear disorder (2% vs. 1%) and pink eye (1% vs. <1%).
In prophylaxis studies in adult patients, adverse events were similar to those seen in the treatment studies. Events reported more frequently in patients taking Tamiflu compared with placebo (incidence greater than or equal to 1%) were nausea (7% vs. 3%), vomiting (2% vs. 1%), diarrhea (3% vs. 2%), abdominal pain (2% vs. 1%), dizziness (1% vs. 1%), headache (18% vs. 18%) and insomnia (1% vs. 1%). In a household prophylaxis trial that included patients one to 12 years old, adverse events were similar to those observed in pediatric treatment studies, with GI events being the most common.
The concurrent use of Tamiflu and live attenuated influenza vaccine (LAIV) intranasal has not been evaluated. However, due to the possibility for interference between these products, LAIV should not be given within 2 weeks before or 48 hours after taking Tamiflu, unless it is deemed appropriate by your doctor. Trivalent inactivated influenza vaccine can be administered at any time relative to use of Tamiflu.
Tamiflu is available for the treatment of influenza in more than 80 countries worldwide.
About Roche
Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J., is the U.S. pharmaceuticals headquarters of the Roche Group, one of the world's leading research-oriented healthcare groups with core businesses in pharmaceuticals and diagnostics. For more than 100 years in the U.S., Roche has been committed to developing innovative products and services that address prevention, diagnosis and treatment of diseases, thus enhancing people's health and quality of life.
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1. Whitley, R. et al. Early oseltamivir initiation produces marked reductions in illness duration, symptom severity and secondary complications in children with influenza. Options for the Control of Influenza VI Conference 2007.
2. Whitley, R. et al. Oral oseltamivir treatment of influenza in children. Pediatric Infectious Disease Journal 2001. 20: 127-33.
3. www.cdc.gov/flu/keyfacts.htm
4. Thompson, WW. et al. Influenza- Associated Hospitalizations in the United States. Journal of the American Medical Association 2004; Vol. 292, No. 11, 1333-40.
5. National Institute of Allergy and Infectious Diseases. "Flu." Retrieved on 2/15/07. http://www.niaid.nih.gov/factsheets/flu.htm.
6. Dolin R. Influenza - interpandemic as well as pandemic disease. New England Journal of Medicine 353; 24. P. 2535-37. December 15, 2005
RocheCONTACT: Terence Hurley of Roche, +1-973-562-2882,terence_j.hurley@roche.com; or Sue Preziotti of Fleishman-Hillard,+1-212-453-2144, preziots@fleishman.com