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Tamiflu and Amantadine Prevention of H5N1 Bird Flu

Recombinomics Commentary

September 17, 2005

She is working to see if combining flu drugs into cocktails will provide better protection and has found some indication that they do. Tamiflu and amantadine may work well together.

The above comments on synergies between Tamiflu and amantadine have not been well covered in the media.  Most of the attention is focused on Tamiflu, but the view paints a partial picture of the anti-viral options.

Tamiflu has been the focus of most H5N1 anti-viral reports.  This focus was increased in the recent ABC Primetime show on avian influenza preparedness.  The report raised the consciousness of the American public and the Tamiflu portion focused on stockpile shortages in general and the US shortage in particular.  The emphasis on Tamiflu is due to the fact that the H5N1 isolated from patients in Vietnam and Thailand was amantadine resistant, so the only class of antivirals available was the neuramindase inhibitors, and only Tamiflu was readily available.

However, that availability has been impaired by countries stockpiling Tamiflu, coupled with a limited production capacity.  Thus, most purchase requests are back-ordered and attention has focused on limited supplies.  However, the utility of Tamiflu is also an issue, because although it has been shown to inhibit H5N1, the inhibition has only been partial at FDA approved doses, so higher doses may be required.  Moreover, like all anti-virals, the effectiveness quickly diminishes, so it is limited to the time that the antiviral is being taken.  Prophylactic courses require 10 pills for 10 days, so use over a extended period of time greatly increases the number of courses per person, which has strong cost and availability implications.

The other neuramindae inhibitor, Relenza, has been made in very limited quantities.  However, increased public awareness and demand may result in an increased availability of Relenza.

However, the H5N1 being spread in Russia, Kazakhstan, and Mongolia has brought the amantadines into the antiviral spotlight.  16 sequences from Qingahi Lake in China have been published, and none have amantadine resistance markers.  Similarities in sequences between isolates from Qinghai Lake in China and Chany Lake in Russia suggest that most or all sequences of H5N1 from wild birds are amantadine sensitive.  The amantadines are sold as Symmetrel (amantadine) and Flumadine (rimantadine) and are much less expensive and more widely available because they are off patent and sold by generic drug companies.  Although resistance can develop, thus far there is no evidence of resistance in H5N1 from wild birds in the countries listed above.

Because the amantadines target one gene (M2) and the neuraminidase inhibitors target another gene (NA), the two drugs can be taken together and will compliment each other, as long as both targeted genes are susceptible to each drug class


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