Treatment with
rimantadine of
influenza in children and the potential development of resistance in clinical isolates associated with
therapy have not been previously studied. We compared
rimantadine to
acetaminophen therapy in a controlled, double-blind study of 91 children with
influenza-like illness. Of 69 children with proven
influenza A/H3N2
infection, 37 received
rimantadine and 32 received
acetaminophen for five days. Children receiving
rimantadine showed significantly greater reduction in
fever and improvement in daily scores for symptoms and severity of illness during the first three days. Viral shedding also diminished significantly during the first two days but subsequently increased such that by days 6 and 7 the proportion of children shedding virus, as well as the quantity of virus shed, was significantly greater in the
rimantadine group. During the seven-day study, of the 22 children in the
rimantadine group with serial isolates tested, ten (45.5%) had resistant isolates compared with two (12.5%) of those with serial isolates in the
acetaminophen group (P less than .03). Thus, of the total 37 children in the
rimantadine group, 27% were found to have resistant isolated compared with 6% in the total group receiving
acetaminophen (P less than .04). Furthermore, the mean inhibitory concentration of
rimantadine increased with time in the
rimantadine group (r = .4, P = .002) but not in the
acetaminophen group.
Rimantadine therapy, thus, appears to be significantly more effective than
acetaminophen in ameliorating the clinical signs and symptoms of
influenza in children. Treatment with
rimantadine was also associated with increased viral shedding after the medication was discontinued and with the development of resistance in the clinical isolates, the significance of which is unknown.