12 January 2000

Dear Health Care Professional:

Diagnostic and therapeutic decisions for patients with symptoms of influenza involve many factors, including consideration of whether to prescribe one of the four drugs currently approved for treatment of influenza. Two of these drugs, amantadine (Symmetrel∆ and others) and rimantadine (Flumadine∆), have been available for many years in the United States. The recent approval of, and promotional activities for, two additional drugs, zanamivir (Relenza∆) and oseltamivir (Tamiflu∆), have increased attention to, and interest in, the role of specific anti-viral therapy in this disease. 

Given that influenza is now occurring in many areas of the country, FDA is issuing this public health advisory to health care professionals to remind prescribers of important clinical decisions that need to be made when considering use of anti-viral drugs for treatment of patients with signs and symptoms of influenza.

The following three considerations are important primarily for two reasons. First, they are important in identifying patients who are appropriate candidates for anti-viral therapy. Secondly, they are important in recognizing patients who may be at risk for serious adverse outcomes from other non-influenza diagnoses or from adverse events potentially related to anti-influenza therapy.

Vaccination remains the primary method of preventing and controlling influenza. 

Always consider the possibility of primary or concomitant bacterial infection when making treatment decisions for patients with suspected influenza. 

When initiation of anti-viral therapy alone is considered on a presumptive basis, ongoing clinical assessment and diagnostic evaluation of the patient continues to be important. FDA has received several reports of patients with serious bacterial infections who initially had influenza-like symptoms and whose bacterial infections progressed during treatment with antiviral drugs alone. Prescribers should be aware that patients with severe influenza-like illness, especially patients with chronic medical conditions or complicated manifestations of acute illness, might have significant bacterial infections instead of, or in addition to, viral illness. These anti-viral products have no activity against bacterial infections. Appropriate anti-bacterial therapy should be initiated whenever bacterial infection is suspected.

Use special caution if prescribing Relenza∆ to patients with underlying asthma or chronic obstructive pulmonary disease (COPD). 

FDA has received several reports of deterioration of respiratory function following inhalation of Relenza∆ in patients with underlying asthma or COPD. Causal relationships with drug therapy are extremely difficult to evaluate in the setting of complex medical processes, but the possibility can not be excluded that an acute decline in respiratory function may contribute to a fatal outcome in patients with a complicated pre-existing medical history and pulmonary compromise. The Relenza∆ package insert contains important precautionary information regarding risks of bronchospasm in patients with underlying airway disease and regarding the lack of proven efficacy in such persons. If a decision is made to prescribe Relenza∆ for a patient with underlying airway disease, this should be done with careful consideration of the potential risks and benefits. In such patients, Relenza∆ should be used under conditions of careful monitoring, proper observation and appropriate supportive care, including the availability of short-acting bronchodilators.

The evidence for use of anti-viral drugs to treat influenza is based principally on studies in patients with uncomplicated influenza. There is not clear evidence for safety and efficacy in persons with underlying respiratory or cardiac diseases, or in persons with complications of an acute influenza episode (for example, viral or bacterial pneumonia). Such patients may require extensive supportive and adjunctive care. Anti-viral therapy has not been shown to reduce the need for such care and monitoring.

All health care professionals are encouraged to report any serious adverse event associated with the use of anti-viral drugs for influenza to the FDA's MedWatch program at 1-800-FDA-1088 (fax 1-800-FDA-0178), or to the respective pharmaceutical manufacturers:

Sincerely yours,

Murray M. Lumpkin, M.D.
Deputy Center Director (Review Management)
Center for Drug Evaluation and Research
Food and Drug Administration