Antiviral Therapy for Pandemic Influenza A (H1N1) Infection: Dosing, Combination Therapy, and Resistance

Publication Summary

In the review “Antiviral Therapy for Pandemic Influenza A (H1N1) Infection: A Meta-Analysis”, the evidence behind the efficacy of antiviral therapy and prophylaxis for pandemic influenza A (H1N1) (pH1N1) infection was addressed.

A number of other ancillary issues arose with regard to therapy for adults during the 2009 influenza A (H1N1) pandemic. These include route of drug administration, appropriate antiviral dosing, the use of combination therapy, and the development of antiviral resistance. This review will focus on the evidence that emerged during the 2009 pandemic on these topics.

Key Points:

• Neuraminidase inhibitors, oseltamivir and zanamivir, were the drug of choice for pandemic influenza A (H1N1) (pH1N1) infection.
• The standard recommended dose of oseltamivir for adults with pH1N1 infection is 75 mg orally twice daily.
• The bioavailability of oseltamivir in critically ill patients with pH1N1 infection was shown to be comparable to that of healthy ambulatory patients, suggesting that optimal viral suppression could be achieved and that doses higher than 75 mg twice daily were unlikely to be of any additional benefit.
• The volume of distribution for oseltamivir carboxylate was similar between morbidly obese patients and non-obese control patients with pH1N1 infection, indicating that no dose adjustment was needed.
• Although oseltamivir carboxylate levels were 30% lower in pregnant patients than in non-pregnant women, the active drug levels were well above those required to inhibit viral replication.
• Combination therapy with multiple antivirals, depending on the combination used, may have synergistic effect against pH1N1.
• Oseltamivir resistance in influenza A viruses is conferred by a mutation in the neuraminidase gene causing an amino acid change in the protein. To date, the prevalence of resistant pH1N1 remains low.