Studies: Antiviral prescribing reflects CDC guidance, flu activity

Jun 11, 2012 (CIDRAP News) – Clinicians are heeding antiviral prescribing guidance changes made over the past decade because of antiviral resistance and a greater focus on protecting high-risk patients, particularly during the 2009 H1N1 pandemic, researchers reported today.

The report is one of two new studies on antiviral dispensing published in Influenza and Other Respiratory Viruses. Both compared data from prescribing databases with US Centers for Disease Control and Prevention (CDC) flu surveillance data and found that antiviral prescription trends are a useful adjunct for monitoring flu patterns.

Prescribing reflected CDC guidance
In the first study, researchers from eight Vaccine Safety Datalink (VSD) Project medical care organizations tracked antiviral medication dispensing from January 2000 through June 2010. The VSD collects vaccination and medical care data on more than 9 million members of certain medical care organizations based in six states: Minnesota, Wisconsin, Washington, California, Massachusetts, and Oregon.

The investigators compared the patterns against the backdrop of changing antiviral recommendations, and there were some notable ones during that period. Until now, few studies have assessed the impact the recommendations had on antiviral prescribing patterns, the authors report.

In 2006 when 91% of H3N2 viruses were resistant to adamantanes, the CDC recommended that clinicians stop using amantadine and rimantadine.

During the 2008-09 season, 98% of seasonal H1N1 viruses were resistant to oseltamivir (Tamiflu), which prompted a recommendation that zanamivir (Relenza) or a combination of oseltamivir and an adamantine be used. When the 2009 H1N1 pandemic virus emerged a few months later, lab experts found that it was susceptible to osteltamivir, and health officials recommended using the drug as early treatment, even without lab testing and especially for high-risk groups.

The group found that antiviral use reflected CDC guidelines. In 2006, clinicians avoided adamantanes. During the 2009 H1N1 pandemic, 97% of oseltamivir dispensings were to patients who weren't tested for influenza, and 31% went to those who weren't assigned an influenza diagnosis.

Also, 46% of oseltamivir prescriptions were written for patients with underlying conditions, including pregnancy. Compared with the prepandemic period, a much higher percentage of oseltamivir prescriptions were written during the pandemic for pregnant women.

Researchers also found a strong correlation between weekly dispensing patterns and the percentage of positive influenza tests from the National Respiratory and Enteric Virus Surveillance System, one of the markers the CDC uses to track flu activity. Researchers found that the patterns were similar at both the local and regional levels.

The investigators noted that the dispensing rates could be an underestimate, because some insurance plans had minimal pharmacy coverage, so dispensing data wouldn't have been recorded.

They also noted that they weren't able to directly measure, for example, the proportion of chronic pulmonary disease patients with respiratory illness who were treated with antivirals and that the system wasn't able to capture those who received oseltamivir during the pandemic through telephone dispensing methods.

Prescribing paralleled flu activity
The second study was conducted by researchers at the US Food and Drug Administration (FDA) who used its proprietary outpatient data to gauge weekly antiviral prescribing patterns during the 2009 H1N1 pandemic. They assessed whether antiviral prescribing trends followed national patterns for doctors' visits for flulike illness, another marker the CDC uses to assess the nation's flu activity.

The researchers focused on April 2009 to April 2010, along with four antivirals prescribed in outpatient settings: oseltamivir, zanamivir, amantadine, and rimantadine. One of the databases the FDA used captures about 80% of the US drug market, and another one tracks about 2 billion prescriptions each year from retail pharmacy chains.

Weekly prescriptions of all antivirals, even the ones for which the 2009 H1N1 virus showed resistance, followed doctors' visit trends, the group reported. Oseltamivir was the primary influenza drug prescribed during the 2009 H1N1 pandemic and garnered 87% of the total antiviral market during the study period.

After the pandemic virus emerged and a nationwide public health emergency was declared, oseltamivir prescriptions saw a 30-fold increase, and zanamivir showed a ninefold increase. During the second pandemic wave that started in August 2009, oseltamivir prescriptions rose again, peaking in late October and leveling off to preseasonal flu levels by early December. The pattern for zanamivir was similar.

Some of the study limitations were that age was missing from a large percentage of the prescriptions covered in the study and that data on indications wasn't available, the authors noted. Also, amantadine has an indication for Parkinson's disease, and it's not clear how many of the prescriptions of that drug were specific to flu.

Though the system couldn't account for possible stockpiling, the researchers didn't see much sign of antiviral prescriptions ahead of the epidemic curve.

The researchers said monitoring prescriptions during a pandemic was a useful addition to other flu surveillance data and provided insights into the potential for shortages, such as the one that occurred with the pediatric oseltamivir suspension.

See also:

Greene SK, Shay DK, Yin R, et al. Patterns in influenza antiviral medication use before and during the 2009 H1N1 pandemic, Vaccine Safety Datalink Project, 2000-2010. Influenza Other Respi Viruses 2012 Jun 11 [Abstract]

Borders-Hemphill V, Mosholder A. US utilization patterns of influenza antiviral medications during the 2009 H1N1 influenza pandemic. Influenza Other Respi Viruses 2012 Jun 9 [Abstract]

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