Use of amantadine and rimantadine in the treatment of influenza is limited by their lack of activity against influenza B, by the rapid emergence of strains that are resistant to amantadine and by reported adverse effects of these agents on the central nervous system. Medical Letter consultants reviewed data on two neuraminidase inhibitors, zanamivir and oseltamivir, in the treatment of influenza.

Neuraminidase is a glycoprotein on the surface of the influenza virus that destroys the infected cell's receptor for viral hemagglutinin. Inhibition of neuraminidase causes a decrease in the release of virus from infected cells. Neuraminidase inhibitors appear to exert activity against all strains of influenza A and B.

Because zanamivir is poorly absorbed in the gastrointestinal tract, it is formulated as a dry powder for inhalation. Most of the drug is deposited in the throat; approximately 20 percent of the inhaled dose reaches the lungs. The oral neuraminidase inhibitor oseltamivir is well absorbed from the gastrointestinal tract. Bioavailability following ingestion is approximately 80 percent. Both drugs are excreted unchanged in the urine.

In a four-week trial of zanamivir prophylaxis during the influenza season, the drug was 67 percent effective in preventing influenza and 84 percent effective in preventing associated febrile illness. This study included 1,107 patients. A six-week trial of oseltamivir prophylaxis found the drug to be 74 percent effective in preventing influenza. This study included 1,559 adults. Neither drug has been labeled for prophylactic use.

Combined data from two double-blind placebo-controlled trials in nonimmunized adults with influenza symptoms for fewer than 48 hours demonstrated that zanamivir, in a dosage of 10 mg twice daily for five days, decreased the time to improvement by an average of one day. In patients with influenza symptoms but without laboratory-confirmed influenza, zanamivir decreased the time to improvement by about 17 hours. The drug had no effect when treatment was initiated more than 30 hours after the onset of symptoms. Another study revealed that the median duration of symptoms was shortened from 6.5 to 5 days. Compared with patients who did not receive zanamivir, those who received it had a lower incidence of influenza-related complications that required antibacterial therapy.

Oseltamivir, in a dosage of 75 to 150 mg orally twice daily for five days, was found to decrease the severity of symptoms and to shorten the average duration of illness from 4.5 to 3 days. As with zanamivir, oseltamivir also was associated with a decrease in the rate of respiratory complications that required antibiotic therapy.

No comparative data exist for these two neuraminidase inhibitors nor for amantadine or rimantadine versus neuraminidase inhibitors.

Studies indicate that adverse effects are uncommon with zanamivir. They include nasal and throat discomfort, headache and cough. Bronchospasm has been reported in patients with asthma. Oseltamivir has been associated with nausea, vomiting and headache. To minimize gastrointestinal effects, oseltamivir should be taken with food.

Neither drug interferes with the antibody response to influenza vaccine. Resistance to neuraminidase inhibitors can occur but appears to be uncommon in immunocompetent adults.

The recommended dosage of zanamivir is 10 mg twice daily for five days. The adult dosage of oseltamivir is 75 mg orally twice daily for five days. Neither drug is recommended for use in children.

Medical Letter consultants conclude that initiation of zanamivir or oseltamivir therapy within 30 hours of the onset of influenza symptoms can shorten the duration of symptoms and decrease the incidence of complications. However, they believe that in actual practice the effectiveness of these drugs may be limited, in part because of lack of efficacy if symptoms have been present for more than 30 hours. Moreover, the need to use an inhalation device with zanamivir may limit its use. These agents may prove more practical for use as prophylaxis against influenza in family members of persons with influenza, and in nursing homes or other special circumstances. Medical Letter consultants state that neither drug is a substitute for influenza vaccination.