Trends of Oseltamivir Usage in the United States during the 2009 Influenza A (H1N1) Pandemic

CDR John K. Iskander LCDR Craig Hales

Charbel el-Bcheraoui Robert T. Chen

Centers for Disease Control and Prevention

Detection of Novel H1N1 Virus

• March 2009• 2 cases of febrile respiratory illness

in children (un-related, no pig contact)

• Residents of adjacent counties in southern California, ill in late March

• Novel swine influenza A (H1N1) virus detected at CDC on April 15th,17th

• Both viruses genetically identical• Contain a unique combination of

gene segments previously not recognized among swine or human influenza viruses in the United States

Retrospective evidence of respiratory illness outbreaks in Mexico (February/March)

April 26, 2009US declares National Public Health Emergency

June 11, 2009WHO declares Global pandemic of novel influenza A (H1N1) virus

Retrospective evidence of respiratory illness outbreaks in Mexico (February/March)

April 26, 2009US declares National Public Health Emergency

June 11, 2009WHO declares Global pandemic of novel influenza A (H1N1) virus

Pandemic H1N1: Disease burden estimates

• In United States, as of 3/13/2010:

– 59.98 million cases– 270, 435 hospitalizations– 12, 271 deaths

• Mean age of deaths 37 years

– Source: CDC website

Influenza Antivirals: Background• Treatment of suspected or confirmed influenza with antiviral medications

is one important strategy to reduce morbidity and mortality caused by the 2009 pandemic influenza A (H1N1) virus (pH1N1)

• The pandemic strain has been susceptible to neuraminidase inhibitors (NAI) such as oseltamivir (> 99% of isolates)

• NAI (oseltamivir, zanamivir) antiviral treatment is recommended* as soon as possible for:

• All hospitalized patients with suspected, probable, or confirmed 2009 influenza A (H1N1) virus infection

• Outpatients with high-risk conditions (including children < 2 years old, pregnant women and women up to 2 weeks post-pregnancy, persons ages 65 and older, persons with chronic conditions - chronic lung disease, diabetes, etc.) with suspected, probable, or confirmed 2009 influenza A (H1N1) virus infection

* Current CDC Antiviral Treatment Recommendations for pH1N1 influenza http://www.cdc.gov/H1N1flu/recommendations.htm

Objectives

• To monitor the usage of influenza antivirals by pH1N1 age-specific risk groups, and to assess related geographic and time trends in the United States

• To evaluate effectiveness of CDC guidance on use of antiviral medicines

Monitoring of Influenza Antiviral Medication Usage

• Through BioSense*, CDC receives anti-infective prescription data from 27,000 pharmacies, representing approximately half of U.S. anti-infective prescription data

– Data include patient demographics (age and sex) and pharmacy zip code

*For more information see www.cdc.gov/biosense

System Description

• BioSense receives prescription data from an electronic prescriptions claims provider in all 50 states and Washington, D.C. as well as U.S. territories. Data are updated every 4 hours

• The data collected concern all prescriptions for anti-infective medicines and include the specific type (brand) and formulation dispensed

• These data cover about 50% of all anti-infective medicines prescribed in the states and represent prescriptions requested at retail pharmacies and approved to be covered by insurance companies

– Coverage range for prescription transactions for the 9 census divisions: mean 49.7%, range 42.9-60.7%

Pharmacies — 27,000 Active

Methods

• Rates of antiviral medication prescribing are calculated using population data from the U.S. Census, and are compared with national and regional measures of influenza disease activity

– % of visits for influenza-like illness (ILI) assessed through U.S. Outpatient Influenza-like Illness Surveillance Network (ILINet)

• We analyzed oseltamivir (Tamiflu®) prescribing data by age groups and federal regions from April through December 2009

Results

Nationwide rates of Rx of Oseltamivir by age groups, USA, 2007-2009

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100

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< 2 yo 2-4 yo 5-18 yo 19-64 yo > 64 yo

Nationwide rates of Oseltamivir prescribing by age groupsUSA, April-December 2009

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< 2 yo 2-4 yo 5-18 yo 19-64 yo > 64 yo

DHHS Regions I-X

Regional rates of Rx of Oseltamivir by age groups, Federal Region 4,April-December 2009

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Regional rates of Rx of Oseltamivir by age groups, Federal Region 9,April-December 2009

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< 2 yo 2-4 yo 5-18 yo 19-64 yo > 64 yo

Summary of Results of Monitoring

• Nationally, highest rates of prescribing were seen shortly after detection of the pandemic in spring of 2009, as well as in September-October of 2009– Two distinct peaks seen in autumn of 2009

• Children (infants, pre-school age, and school age) were prescribed the medication at the highest rates

• Medication prescribing for all ages has sharply decreased since November 2009

Results Details

• School-age children (5-18 years) consistently had the highest prescribing rates, with a peak of > 500 prescriptions/100,000 population during September 2009

• Pre-school age children (2-4) had similar prescribing rates, reaching 450/100,000 in both September and October

• Patterns of prescribing for infants generally paralleled those seen for older children but with lower peak rates (350/100,000)

• After the initial May peak, prescribing rates for working age adults (18-64) and the elderly (65 and over) were < 200 courses/100,000

• Regional prescribing patterns clustered geographically, with prescribing rates in contiguous regions increasing and decreasing synchronously

Interpretation of findings

• Prescribing rates have been highest overall among pediatric age groups, who are at high risk of H1N1 illness

• Lower rates of prescribing for those 65 and over are

consistent with low rates of H1N1 disease in this age group

• Rates of prescribing were closely related to levels of influenza disease activity, both nationally and regionally

• Despite widespread prescribing of oseltamivir, so far no detection of significant levels of viral resistance or new safety concerns

Strengths and Limitations• Strengths

– Data updated frequently– Significant population coverage– Ability to generate age adjusted prescribing rates– Exploring ability to provide data linked to claims

• Limitations

– Ecologic analysis; no linkage to patient level diagnostic information – No data from hospital pharmacies– No coverage for self-pay or those with no prescription insurance

coverage

Conclusions

• Prescribing rates were highest overall among pediatric age groups, who are at high risk of H1N1 illness

• Rates of prescribing were closely related to levels of influenza disease activity, both nationally and regionally

Future (and Present) Uses of Pharmacy and other Drug Utilization Data

• Monitoring of both infectious and chronic diseases

• Use as denominator data for pharmaceutical safety/adverse event monitoring

• Use by Strategic National Stockpile (SNS) to monitor formulation shortages and adjust stockpile distribution

Antiviral Adverse Event Monitoring – Comparison by Season* December 31, 2009

*Note: AE data lagtime is 2-3 weeks.

Influenza Antiviral-Related Emergency Department Visits, 2006-2007 Season to PresentSource: DAWNLive!

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Oct

-06

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v-0

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f R

epo

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Amantadine Rimantadine Oseltamivir Zanamivir

2007-2008 Season 2008-2009 Season2006-2007 Season

2009 H1N1

*Up-to-date through 12/31/09 (DAWN) and 12/26/09 (BioSense). Note: AE data lagtime is 2-3 weeks.

Antiviral AE Monitoring and Antiviral Dispensing, December 31, 2009

Influenza Antiviral-Related Emergency Department Visits (DAWN Live! ) and Influenza Antiviral Prescriptions (CDC BioSense), October 2008 - Present

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Oct-08 Nov-08 Dec-08 Jan-09 Feb-09 Mar-09 Apr-09 May-09 Jun-09 Jul-09 Aug-09 Sep-09 Oct-09 Nov-09 Dec-09

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Amantadine Rimantadine Oseltamivir Zanamivir Influenza Antiviral Rx's

Acknowledgments

• Taha Kass-Hout and BioSense staff

• CAPT Anthony Fiore, Influenza Division, CDC

• CDR Dan Budnitz, Division of Healthcare Quality Promotion, CDC

Supplemental

Background on BioSense• BioSense is a national program intended to improve the

nation’s capabilities for conducting real-time biosurveillance, and enabling health situational awareness through access to existing data from healthcare organizations across the country

• BioSense receives, analyzes, and evaluates health data from numerous data sources such as emergency rooms, ambulatory care clinics, and clinical laboratories

• For more information: – www.cdc.gov/biosense – http://twitter.com/cdc_biosense

Location of BioSense Pharmacies (N≈27,000)

Antiviral AE Monitoring and Antiviral Dispensing, December 31, 2009