Missed the Shot, Got the Flu, Now What?

With peak flu season approaching, pharmacists are gearing up to help care for patients infected with influenza.

The journal Expert Review of Clinical Pharmacology published a literature review online in October 2016 that discussed existing and emerging therapies for treatment of severe influenza infection.

Around 23,600 Americans succumb to influenza annually. The particular type of influenza strain has clinical implications, and can cause, for example, increased mortality. Different influenza strain mutations raise the possibility of resistance to currently used agents and underscore the importance of developing novel antivirals.

Neuraminidase inhibitors (NAIs) are the most commonly used antivirals for treating the flu, and oseltamivir and zanamivir are recommended as first-line agents. They work by inhibiting the action of the viral enzyme neuraminidase (NA) that is key to viral budding from the cell. The CDC and WHO currently recommend oseltamivir, zanamivir, and peramivir, with peramivir available as an intravenous formulation. Resistance to these widely used agents is likely to occur in the coming years.

Many novel agents that target different viral mechanisms are in development; these mechanisms include the following:

• Binding viral RNA-dependent RNA polymerases and using small interfering RNA (siRNA) to halt viral transcription
• Cleaving sialic acid residues preventing viral penetration into the cell bind
• Neutralizing influenza using monoclonal antibodies

These agents have demonstrated promising results and show activity against many strains, including those resistant to NAIs. Some of them work synergistically with currently used agents, such as oseltamivir.

The fate of NAIs in regard to viral resistance can be likened to the adamantane drug class. Clinicians prescribed adamantanes—amantadine and rimantadine—widely in the past for influenza prevention and treatment. However, due to their limited coverage and rising global resistance, they are no longer recommended.

Laboratory methods exist to test for antiviral susceptibility, and guidelines recommend testing in certain populations. This can aid in selecting an appropriate antiviral regimen.

With the advent of novel antiviral development, the future holds many possibilities, but clinicians will need to stay vigilant due to rising drug resistance.