Amantadine and rimantadine for influenza A in children and the elderly

The antiviral drug amantadine can prevent some cases of influenza in children, and the related medication rimantadine can reduce fever in youngsters who have the flu, according to a new review of evidence.

The benefits are modest, however.

About a dozen children would need to take amantadine for three to four months to prevent one case of illness. Likewise, rimantadine might relieve fever in infected youngsters within three days, instead of four to eight days without the drug.

The U.S. Centers for Disease Control and Prevention (CDC) does not recommend use of either drug this winter, because recent flu viruses have developed resistance to them. Vaccination remains the primary strategy for flu prevention, says the agency's Web site.

“Nevertheless, there are some instances in which this prevention could turn out to be inadequate,” said Márcia Alvez Galvão, M.D., a pediatric researcher at Federal University of Rio de Janeiro in Brazil and a review co-author. In the case of a worldwide pandemic “antivirals would be of utmost importance,” she added.

Respiratory viruses cause influenza and typically produce symptoms like cough, runny nose, headache and fever. Flu symptoms normally disappear without treatment within three to seven days. Amantadine and rimantadine are only effective against some strains of influenza A, which causes most cases of the illness in humans.

Flu infection can lead to hospitalization, pneumonia and even death, especially among vulnerable populations like children and the elderly. The reviewers had hoped to evaluate use of the two antivirals among older people, but found few studies of this age group.

The review appears in the most recent issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

Review authors reached as far back as 1967 to find eight studies of youths under age 20. The total number of participants receiving amantadine was more than 1,000, while about 250 children received rimantadine.

Neither drug appeared to increase the likelihood of unpleasant side effects such as nausea, diarrhea, rashes or headaches. However, the reviewers note that the safety of amantadine “was not well established.”

The limited benefit of rimantadine in reducing fever suggests that it would be appropriate “only for selected cases in which fever may cause undesirable consequences,” say the reviewers. This could include children in whom fever would interfere with control of other diseases such as diabetes or chronic anemia.

“In the majority of our comparisons, drawing definitive conclusions was impaired by the small number of selected articles and the small sample numbers,” Alvez Galvão said. The authors call for further research in all areas covered by the review: both drugs, both age groups, prevention and treatment, plus safety and efficacy.

There are a number of likely scenarios in which flu prevention through vaccinations could prove inadequate, the authors say. For example, viruses might change after the development of a vaccine for a given year, making it less effective. Alternatively, during a pandemic, vaccine supplies might be inadequate.

“Antiviral agents therefore form an important part of a rational approach to influenza management,” concludes the review.

Fortunately, most circulating flu viruses remain susceptible to two newer antiviral drugs: oseltamivir (Tamiflu) and zanamivir (Relenza). But U.S. reserves contain only a small fraction of the doses needed to treat the nation's children and adolescents during a pandemic, according to the American Academy of Pediatrics (AAP). Furthermore, neither of the newer drugs is licensed for children younger than 1 year.

“It is possible that susceptibility to the older drugs will return some year, although many virologists doubt that,” says John Bradley, M.D., a member of AAP's Committee on Infectious Disease. “Right now, we are behind the curve in finding ways to limit the spread of a pandemic in children even though they are among those most at risk.”

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJL. Amantadine and rimantadine for influenza A in children and the elderly (Review). Cochrane Database of Systematic Reviews 2008, Issue 1.

Interviews: Antonio Alves da Cunha at +55 21 2562 6148 or [email protected]