Amantadine and rimantadine in the prevention and treatment of influenza
Evidence Summaries Level of Evidence = C
In adults, amantadine (AMT) and rimantadine (RMT) may be effective in the prevention and tratment of influenza. In children, AMT may prevent influenza and RMT may shorten fever in the treatment of influenza. In the elderly, there is no evidence on the effect of AMT or RMT in the prevention or treatment of influenza.
A Cochrane review 1 included 35 trials with 27,827 healthy adults. Another Cochrane review 2 included 12 studies with a total of 2,494 subjects (1,586 children and adolescents and 908 elderly).
Prevention: In healthy adult population, AMT prevented 61% of influenza cases (95% CI 35% to 76%; 11 trials, n=4,645) and 25% of influenza-like-illness (ILI) cases (95% CI 13% to 36%; 15 trials, n=17,496; p<0.001 for both results) as compared to placebo. RMT demonstrated comparable effectiveness, but there were only 3 trials (n= 688) and the results for prophylaxis were not statistically significant. In children, a protective effect of AMT (RR 0.11; 95% CI 0.04 to 0.30), but no protective effect of RMT (RR 0.49; 95% CI 0.21 to 1.15) was observed. In the elderly, no protective effect of RMT was observed (RR 0.45; 95% CI 0.14 to 1.41) and there were no studies on AMT.
Treatment: In the treatment of adult´s influenza, both drugs significantly shortened duration of fever compared to placebo (AMT by 0.99 days; 95% CI 0.71 to 1.26, 10 trials, n= 542; RMT by 1.24 days, 95% CI –0.76 to –1.71, 3 trials, n=82). There was no effect on nasal shedding or persistence of influenza A viruses in the upper airways after up to five days of treatment (AMT RR 0.97; 95% CI: 0.76 to 1.24; 3 trials, n=170; RMT RR 0.68; 95% CI 0.30 to 1.53; 3 trials, n= 152). In children, RMT had benefit in the abatement of fever on day three of treatment (RR 0.36; 95% CI 0.14 to 0.91), but no protective effect of AMT was observed (RR 0.37; 95% CI 0.08 to 1.75). There were no studies on the effectiveness of AMT and RMT in the treatment of influenza A in the elderly.
Comment: The quality of evidence is downgraded by inconsistency and limitations in study quality.
Clinical comment: Due to resistance problems, amantade and rimantadine are not considered to be first-line options in the prevention or treatment of influenza. A majority of circulating A(H1N1)- ja A(H3N2) influenza viruses are resistant to these drugs.
1. Jefferson T, Demicheli V, Di Pietrantonj C, Rivetti D. Amantadine and rimantadine for influenza A in adults. Cochrane Database Syst Rev 2006 Apr 19;(2):CD001169 [Last assessed as up-to-date: 25 April 2008] [PMID:16625539]
2. Alves Galvão MG, Rocha Crispino Santos MA, Alves da Cunha AJ. Amantadine and rimantadine for influenza A in children and the elderly. Cochrane Database Syst Rev 2014;11():CD002745. [PMID:25415374].
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