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Prophylactic administration of amantadine hydrochloride diminished significantly the occurrence and severity of experimentally induced Asian influenza illness in double-blind studies conducted in 58 volunteers. No difference in infection (seroconversion) rate was observed but serum neutralizing antibody titers were significantly lower in men receiving amantadine compared to those of control subjects. Reduction in the severity and occurrence of disease and lower postchallenge antibody level are based probably on indirect inhibition of virus multiplication and consequent diminution of antigenic stimulation.

A single double-blind study conducted with 55 volunteers showed clearly that Exp 126 (alpha-methyl-1-adamantanemethylamine hydrochloride, rimantadine hydrochloride), an analogue of amantadine hydrochloride, reduced the occurrence and severity of artificially induced Asian influenza in humans. The infection (or seroconversion) rate in the drug-dosed and placebo-dosed groups was almost 100%, although the increase in serum neutralizing antibody levels was significantly less in the Exp 126-dosed subjects. The infecting influenza virus was recovered only from placebo-dosed controls. Probable untoward reactions from the drug occurred in three volunteers. Two related drugs, amantadine hydrochloride and rimantadine hydrochloride are now available for the prevention of Asian influenza.

Amantadine hydrochloride had a chemotherapeutic effect in patients with naturally occurring Asian influenza during the epidemic of 1967 to 1968. In double-blind clinical trials in which 54 men were treated with amantadine and 48 men received placebo capsules, more rapid defervescence and improvement of some symptoms were achieved in the drug-treated patients. The effect was demonstrable when drug therapy was started approximately 20 hours after the patients became ill. The causative virus was recovered at a high rate during the first four days of therapy in both groups which indicated that the drug did not affect virus shedding. Systemic as well as local antibody titer increases which developed in amantadine-treated patients during convalescence were equivalent to those of the placebo-treated patients.