Antiviral drugs amantadine and rimantadine for preventing and treating the symptoms of influenza A in adults

The drugs amantadine and rimantadine can both help prevent and relieve the symptoms of influenza A in adults, but amantadine has more adverse effects.

The flu can be caused by many different viruses. One type is influenza A, with headaches, coughs and runny noses that can last for many days and lead to serious illnesses such as pneumonia. Amantadine and rimantadine are antiviral drugs. The review of trials found that both drugs are similarly helpful in relieving the symptoms of influenza A in adults, but only when there is a high probability that the cause of the flu is influenza A (a known epidemic, for example). It is likely that neither drug will interrupt the spread of influenza A and by treating symptoms may encourage viral spread in the community by people who are feeling better but are still infectious. Resistance of influenza viruses to amantadine is a serious worldwide problem as shown by recent surveys. Both drugs have adverse gastrointestinal (stomach and gut) effects, but amantadine can also have serious effects on the nervous system. They should only be used in an emergency when all other measures fail.

Authors' conclusions: 

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. Resistance of influenza viruses to amantadine is a serious worldwide problem as shown by recent virological surveillances. Both drugs have adverse gastrointestinal (stomach and gut) effects, but amantadine can also have serious effects on the nervous system. They should only be used in an emergency when all other measures fail.

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Background: 

Amantadine hydrochloride (amantadine) and rimantadine hydrochloride (rimantadine) have antiviral properties, but they are not widely used due to a lack of knowledge of their potential value and concerns about possible adverse effects.

This review was first published in 1999 and updated for the fourth time in April 2008.

Objectives: 

The objective of this review was to assess the efficacy, effectiveness and safety ('effects') of amantadine and rimantadine in healthy adults.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, issue 1), MEDLINE (1966 to April Week 4, 2008), EMBASE (1990 to April 2008) and reference lists of articles.

Selection criteria: 

Randomised and quasi-randomised studies comparing amantadine and/or rimantadine with placebo, control medication or no intervention, or comparing doses or schedules of amantadine and/or rimantadine in healthy adults.

Data collection and analysis: 

For prophylaxis (prevention) trials we analysed the numbers of participants with clinical influenza (influenza-like-illness or ILI) or with confirmed influenza A and adverse effects. Analysis for treatment trials was of the mean duration of fever, length of hospital stay and adverse effects.

Main results: 

Amantadine prevented 25% of ILI cases (95% confidence interval (CI) 13% to 36%), and 61% of influenza A cases (95% CI 35% to 76%). Amantadine reduced duration of fever by one day (95% CI 0.7 to 1.2). 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 (GI) 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 or the course of asymptomatic influenza.

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