Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine. Long-term study of fluticasone propionate aqueous nasal spray in acute and maintenance therapy of nasal polyposis. Safety and prophylactic efficacy of low-dose rimantadine in adults during an influenza A epidemic. Evaluation of amantadine hydrochloride in the treatment of A2 influenzal disease. Administration of amantadine for the prevention of Hong Kong influenza. Evaluation of amantadine in the prophylaxis of influenza A (H1N1) virus infection: a controlled field trial among young adults and high-risk patients. Efficacy and safety of low dosage amantadine hydrochloride as prophylaxis for influenza A. Therapeutic effects of aerosolized amantadine in naturally acquired infection due to influenza A virus. Oral oseltamivir improves pulmonary function and reduces exacerbation frequency for influenza-infected children with asthma.
During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity. Topical steroids are first-line medication to control nasal polyposis (NP), a disease with long-term clinical course.
                The aim of this study was to evaluate the efficacy and safety of fluticasone propionate aqueous nasal spray (FPANS) 200 microg twice a day (bd) after 1 month of treatment, and to compare FPANS 200 microg bd and FPANS 200 microg once a day (od) in maintenance and long-term treatment.
                Double-blind, placebo-controlled, 8-month study with three treatment periods (1-month acute period followed with 1-month maintenance period and 6-month follow-up period) was carried out. Group 1 received FPANS 200 microg bd, during acute, maintenance and follow-up periods, Group 2 received FPANS 200 microg bd during acute period and FPANS 200 microg od during maintenance and follow-up periods, and Group 3 received placebo during acute and maintenance periods and FPANS 200 microg bd during follow-up period. Endpoints were change from baseline in clinic peak nasal inspiratory flow (PNIF), domiciliary evening PNIF, intensity of symptoms and polyposis grade.
                After acute period and maintenance periods, FPANS 200 microg bd was significantly more effective than placebo on all endpoints and more effective than FPANS 200 microg od after 1-month maintenance period on clinic PNIF, evening PNIF, obstruction, percentage of days with no sense of smell and percentage of nights with no disturbances. The two doses were similar on other endpoints. After the 6-month follow-up period, there was no difference between the two doses of FPANS at all efficacy endpoints. The safety profile of FPANS did not highlight any new or unanticipated adverse events.
                The study demonstrated the efficacy of FPANS 200 microg bd in acute treatment and FPANS 200 microg od as a sufficient dose to maintain a long-term efficacy in the treatment for NP. A placebo-controlled, double-blind study to evaluate the safety and prophylactic efficacy of a low dose (100 mg) of rimantadine hydrochloride against naturally occurring influenza in adults was conducted at two sites. After the onset of the influenza season, volunteers (ages, 18 to 55 years) were assigned randomly to receive rimantadine or placebo daily. Subjects were monitored for adverse effects and evidence of influenza virus infection weekly for six weeks. Only 10 (8.7%) of 114 rimantadine recipients and 5 (4.4%) of 114 placebo control recipients reported one or more mild to moderate adverse symptoms, most of which were related to the gastrointestinal or central nervous system. Compared with placebo, low-dose rimantadine was highly effective in the prevention of influenza A virus infection (20 of 110 versus 7 of 112 participants; P less than 0.01) and influenza illness (7 of 110 versus 1 of 112 participants; P = 0.04). Influenza A/Leningrad/87-like (H3N2) virus was recovered from the nasopharynxes of only five placebo recipients. These findings indicate that low-dose rimantadine is well tolerated and highly effective for the prevention of influenza A illness in healthy adults. Amantadine hydrochloride is the first drug to show promise as a practical anti-influenza agent. Several studies demonstrating a prophylactic effect in volunteers with induced A2 disease as well as in patients during A2 outbreaks have created the impetus for therapeutic trials. The widespread A2 influenza epidemic that occurred early in 1968 provided the opportunity for therapeutic evaluation in the USA.A total of 197 prison inmates with proven influenza agreed to participate in the 10-day double-blind evaluation of amantadine (100 mg, twice daily). Onset of therapy was approximately 20 hours after first subjective awareness of illness.Assessment of drug effectiveness was based on rapidity of resolution of illness. There was a significant increase in the number of drug-treated as against placebo patients in the "rapid resolver" group whereas individuals receiving placebo dominated the "slow resolver" group. Analysis of febrile responses indicated that amantadine-treated patients had significantly more rapid defervescence. Virus isolation studies revealed etiologically related virus in 90% of all volunteers during the first 5 days of therapy. It was apparent that clinical improvement was not correlated with disappearance of the virus. Nevertheless, the trials conducted during the influenza season of early 1968 indicated the therapeutic effect of amantadine hydrochloride. Administration of 100 mg, twice daily, for 10 days did not cause any adverse effects. The prophylactic effectiveness of amantadine against A2/Hong Kong influenza was investigated in the course of a double-blind trial in Braşov, Romania, during an epidemic due to the Hong Kong virus that started there in March 1969.Altogether 215 subjects were included in the trial; 112 received 100 mg of amantadine twice daily for 20 days and the remaining 103 received inert placebo tablets. Of the amantadine-treated group, 2 had clinical symptoms diagnosed as influenza (1 of these was a doubtful diagnosis), whereas 20 (1 doubtful) of the placebo group had such symptoms. No case with both clinical symptoms and serologically confirmed influenza (>/=4-fold increase in haemagglutination-inhibition titre) occurred among 77 amantadine-treated subjects for whom paired sera were available but there were 13 such cases among the 74 placebo subjects with paired sera. These differences are statistically highly significant. No serious side-effects were recorded.The authors conclude that amantadine was highly effective in preventing overt disease and discuss indications that suggest that it did not interfere with the development of immunity in persons treated during the incubation period. The usefulness of amantadine in the protection of humans against influenza A (H1N1) virus was evaluated in a double-blind field trial with 555 volunteers in Finland in the winter of 1978. Three populations--patients in a general hospital, adults in a home for the aged, and two groups of military conscripts--were chosen. Epidemic influenza occurred only in the two groups of conscripts: the incidence of serologically verified influenza was 66% and 83% in the groups that received placebo and 43% and 51% in the groups that received amantadine, giving protection rates of 36% (P = 0.05) and 39% (P = 0.001). The evaluation of the effect of amantadine on the occurrence of illness was obscured by concomitant adenoviral infections that caused influenza-like symptoms. No clear difference in the occurrences of side effects was observed between the placebo and amantadine-treated groups; however, a significantly greater number of participants who took 200 mg of amantadine/day (16.9%) stopped medication during the trial as compared with the placebo groups (7.6%) (P < 0.02). The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind, placebo-controlled, randomized studies. In a study of 476 subjects aged 18 to 55 years, adverse reactions were not significantly different between the group receiving 100 mg/day amantadine and the placebo group but significantly greater in the group given 200 mg/day (P less than 0.009). The influenza attack rate in this study was too low to assess efficacy. In an experimental challenge study of influenza A/Beth/1/85 in 78 subjects of similar age the prophylactic administration of 50 mg, 100 mg or 200 mg/day doses of amantadine were more effective than placebo in preventing influenza illness (P less than 0.02, 66, 74 and 82% protection, respectively), and in suppressing viral replication (P = 0.02). There was no significant difference between amantadine groups in influenza illness or viral shedding. Compared with the placebo group the 100 and 200 mg amantadine groups showed a significant decrease in infection rate (100 mg: 40% protection: P = 0.012; 200 mg: 32% protection: P = 0.045) whereas the 50 mg group did not (20% protection: P = 0.187). These results suggest that 100 mg/day of amantadine will reduce toxicity but maintain the prophylactic efficacy seen with 200 mg/day. The effect of small-particle aerosol therapy with amantadine was assessed in a randomized, double-blind study of 20 patients with naturally acquired influenza A virus infection. Aerosol treatments of 20 min with either distilled water or with amantadine hydrochloride (1.0 g/100 ml of distilled water) were given three times a day for four days. The amantadine-treated patients experienced a significantly more rapid resolution of clinical signs and symptoms when compared with placebo-treated patients. The resolution of fever was similar for both groups. Aerosol delivery of amantadine did not affect the frequency of viral isolation from upper respiratory tract secretions but was associated with a trend toward reduced quantity of viral shedding. Serial pulmonary function tests found no important differences between the groups. Amantadine-treated patients experienced a greater frequency of mild local side effects (rhinorrhea, nasal irritation) during aerosol exposures, but aerosol treatments did not cause any apparent decline in pulmonary function. Among asthmatic children, influenza is associated with increased hospitalizations. Although vaccination is safe and effective among asthmatic children, its protective efficacy varies and uptake rates can be low. In comparison, oseltamivir (Tamiflu) is effective against all influenza strains and can reduce the severity and duration of influenza among adults and children. This study determined the effects of oseltamivir among influenza-infected children with asthma.
                Asthmatic children (6-12 years of age) were randomized to receive oseltamivir (2 mg/kg) or placebo twice daily, as a syrup. The primary efficacy endpoint was the time to freedom from illness. Secondary endpoints included the area under the symptom score-hour curve, the proportion of patients with asthma exacerbations and changes in forced expiratory volume at 1 second during the dosing period. Analysis was performed for both the intent-to-treat infected (n = 179) and per protocol (n = 162) populations.
                The primary endpoint for this study was not met. Oseltamivir tended to reduce the time to freedom from illness in the intent-to-treat infected population (10.4 hours, 8%; P = 0.5420), the per protocol population (24.3 hours, 17%; P = 0.1607) and patients who started treatment <24 hours after symptom onset (39.8 hours, 25%; P = 0.0780). However, an improvement in pulmonary function was observed. The improvement in forced expiratory volume at 1 second was significantly greater among oseltamivir-treated patients (10.8% versus 4.7%; P = 0.0148). Oseltamivir-treated patients also experienced fewer asthma exacerbations up to day 7 (68% versus 51%; P = 0.031). Oseltamivir was safe and well-tolerated.
                Oseltamivir is safe and well-tolerated among asthmatic children, may reduce symptom duration and helps improve lung function and reduce asthma exacerbations during influenza infection.
There is insufficient good evidence to enable robust conclusions to be made about Oscillococcinum® in the prevention or treatment of influenza and influenza-like illness. Our findings do not rule out the possibility that Oscillococcinum® could have a clinically useful treatment effect but, given the low quality of the eligible studies, the evidence is not compelling. There was no evidence of clinically important harms due to Oscillococcinum®.