***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The efficacy and safety of prophylactic low dose amantadine hydrochloride was assessed in two double-blind , placebo-controlled , r and omized 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 single-dose pharmacokinetics of amantadine hydrochloride and rimantadine hydrochloride were compared in a r and omized , two-period , crossover study involving six young ( less than or equal to 35 years ) and six elderly ( less than or equal to 60 years ) adults . Subjects ingested single 200-mg oral doses after an overnight fast , and serial plasma ( 0 to 96 h ) , nasal mucus ( 0 to 8 h ) , and urine ( 0 to 24 h ) sample s were collected for assay of drug concentration by electron capture gas chromatography . For both groups combined , rimantadine differed significantly from amantadine in peak plasma concentration ( mean + /- st and ard deviation , 0.25 + /- 0.06 versus 0.65 + /- 0.22 micrograms/ml ) , plasma elimination half-life ( 36.5 + /- 15 versus 16.7 + /- 7.7 h ) , and percentage of administered dose excreted unchanged in urine ( 0.6 + /- 0.8 versus 45.7 + /- 15.7 % ) . No significant age-related differences were noted for rimantadine .  Urinary excretion ( 0 to 24 h ) of  rimantadine  and its hydroxylated metabolites averaged 19 % of the administered dose . The maximum nasal mucus drug concentration was similar for both drugs ( 0.42 + /- 0.25 versus 0.45 + /- 0.32 micrograms/g ) , and the ratio of maximum nasal mucus to plasma concentration was over twofold higher after rimantadine than after amantadine . These findings may in part explain the clinical effectiveness of rimantadine in influenza A virus infections at dosages that have lower toxicity than those of amantadine The therapeutic activity of rimantadine and its relationship to the shedding of drug-resistant influenza A virus were assessed in two r and omized , double-blind , placebo-controlled trials involving patients with laboratory-documented influenza A virus ( H3N2 subtype ) illness of 2 days ' duration or less . In a family-based study , rimantadine treatment for 10 days ( 24 children and adults ) was associated with significant decreases in the number of days to a 50 % reduction in symptoms ( mean difference , 2.5 days ) , days of fever ( 1.6 days ) , and days of restricted activity ( 1.5 days ) compared with the results obtained with  placebo-treated patients ( 32 children and adults ) .  Drug-resistant virus was recovered from eight ( 33 % ) of the rimantadine recipients on day 5 . No differences in patient demographics or illness severity at the time of enrollment in the study were apparent between those who shed resistant virus and those who did not . Illness resolution tended to be slower in those who shed resistant virus compared with that in those who did not . In a study of adults treated for 5 days ( six treated with rimantadine , six treated with placebo ) , resistant virus was recovered in three rimantadine recipients by day 3 of treatment . The results indicate that drug-resistant influenza A virus ( H3N2 ) can be recovered from rimantadine-treated children and adults as early as 2 days after starting treatment , but that rimantadine retains a net therapeutic benefit compared with that of placebo The relative toxicities of amantadine and rimantadine were compared in a double-blind , placebo-controlled study involving healthy adults . In separate studies , drugs were administered at a dosage of 200 mg/day ( 52 volunteers ) or 300 mg/day ( 196 volunteers ) for 4.5 days . Both drugs were well tolerated at the lower dosage . At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system ( nervousness , lightheadedness , difficulty concentrating ) and sleep ( insomnia , fatigue ) complaints compared with rimantadine or placebo recipients . Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability . Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients . Because of better tolerance at higher dosage , rimantadine offers more promise than amantadine for treatment of influenza A virus infections 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 1-Adamantanamine hydrochloride ( aminoadamantane ) has been shown to inhibit the multiplication of influenza A viruses in cell cultures , organ cultures and experimentally infected mice . An epidemic of influenza in Great Britain in the winter of 1967 - 68 provided the opportunity to study the prophylactic effect of aminoadamantane in the family environment and this paper reports the results of further observations in January-March 1969 during an influenza epidemic due to A2/Hong Kong/68.In a double-blind , placebo-controlled investigation of aminoadamantane given prophylactically , in doses of 100 mg every 12 hours for 10 days , no protective effect of the drug was demonstrated . In view of the positive effect of the drug in the earlier study during the winter of 1967 - 68 , and the apparent sensitivity of the virus strain , an explanation involving the very high incidence of individuals possessing HI antibody of less than 1:12 is offered Abstract The therapeutic activity of 1-adamant-anamine hydrochloride ( amantadine ) was investigated in a double-blind study of patients with clinical ly and serologically confirmed influenza A 2 /Hong Kong/68 infections who continued to live in their normal domestic environment . There was a significant reduction ( In a double-blind , placebo-controlled study , the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined . Healthy , working adults ingested either 200 ( n = 52 ) or 300 mg ( n = 196 ) per day in divided doses for 4.5 days . Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- ( 140 versus 300 ng/ml for rimantadine and amantadine , respectively ; P less than 10(-5 ) ) or 200-mg doses ( 310 versus 633 ng/ml ; P less than 10(-5 ) ) . The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine , but the plasma levels of toxic and nontoxic subjects overlapped extensively . At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms ( 33 % of amantadine versus 9 % of rimantadine recipients ; P less than 0.001 ) and sleep disturbance ( 39 versus 13 % ; P less than 0.001 ) , but not gastrointestinal symptoms ( 19.5 versus 16.0 % ) . However , no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations . Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations In a boarding school for boys , where routine influenza vaccination is carried out annually , 267 boys were given amantadine ( 100 mg daily ) and 269 received no specific treatment during an influenza A ( H1N1 ) outbreak . 3 boys receiving amantadine and 29 boys receiving no medication had laboratory-proven influenza A. There are circumstances when the prophylactic use of amantadine may be justified for the control of influenza A outbreaks in boarding schools and other institutions where high attack-rates are experienced In a r and omized , double-blind placebo-controlled clinical trial , we evaluated the prophylactic effectiveness of  rimantadine  in children ( ages 1 to 18 years ) against infection with influenza A ( H3N2 ) and associated illness and the prevention of transmission of infection to adult members of the child 's family . One hundred ten volunteers from 29 families completed this study during a naturally occurring outbreak of influenza A ( H3N2 ) . Influenza infections , defined as a positive viral throat culture or a 4-fold increase in antibody titer , occurred in 31.0 % of children in the placebo group and 7.4 % in the rimantadine group ( P = 0.026 ) . Clinical illness with laboratory evidence of influenza infection occurred in 24.1 % of children in the placebo group and none in the rimantadine group ( P = 0.007 ) . Rimantadine was well-tolerated by the children , with no significant difference in reported adverse effects between the placebo and rimantadine groups . A combined analysis by families of these data and those of our similarly design ed 1984 study , revealed that families in whom the children were given rimantadine had a significantly lower rate of influenza A infection and influenza-like illness compared with the families in whom the children were given placebo ( 68.8 % vs. 18.8 % , P less than 0.001 ) and ( 56.3 % vs. 12.5 % , P less than 0.001 ) , respectively . We conclude that rimantadine prophylaxis of children appears to be an effective method to prevent influenza A ( either H1N1 or H3N2 ) infection and illness in children Prophylactic administration of amantadine in doses of 100 mg . twice a day offered statistically significant protection against influenza A2 infection in a double-blind field trial involving 391 medical student volunteers during the influenza A2 Hong Kong epidemic in Helsinki in the winter of 1969 . Serologically verified influenza , as measured by complement fixation and /or haemagglutination inhibition , occurred in 27 out of 192 students in the  amantadine  group against 57 out of 199 in the placebo group , giving a protection rate of 52 % To determine whether rimantadine can protect family members from acquiring influenza A viral illness and to assess the possible selection of drug-resistant strains of virus , we conducted a r and omized , double-blind , placebo-controlled study in three communities during two influenza seasons . When influenza A occurred in a family , the members ( including the index patient ) were given either rimantadine ( adult oral dose , 200 mg per day ) or placebo for 10 days . The presence of illness was monitored by daily recording of symptoms and temperature measurements ; infection was determined by isolation of the virus and by serologic studies . Among households with documented influenza A infections , symptomatic illness occurred in one or more contacts in 10 of 28 families treated with rimantadine and in 10 of 209 families treated with placebo .  Asymptomatic secondary influenza A infections were found in five families assigned to receive rimantadine and in four families assigned to receive placebo . Rimantadine-resistant strains of influenza A virus ( H3N2 subtype ) with mutations consisting of single amino acid changes in the M2 protein ( residue 27 , 30 , or 31 ) were recovered from eight index patients and five contacts treated with rimantadine . There was apparent transmission of drug-resistant strains of virus in six contacts with secondary illnesses in five families . We conclude that when index patients are treated concurrently , rimantadine 
    Output:
    
Rimantadine demonstrated comparable effectiveness , but there were fewer trials and the results for prophylaxis were not statistically significant .
Both amantadine and rimantadine induced significant gastrointestinal adverse effects .
Adverse effects of the central nervous system and study withdrawals were significantly more common with amantadine than rimantadine .
Neither drug affected the rate of viral shedding from the nose and the course of asymptomatic influenza .
Amantadine and rimantadine have comparable efficacy and effectiveness in relieving or treating symptoms of influenza A in healthy adults , although rimantadine induces fewer adverse effects than amantadine .
The effectiveness of both drugs in interrupting transmission is probably low .