A Linezolid Prior Authorization Program: Clinical and Economic Outcomes | Page 3

Published Online: April 16, 2014
Catherine I. Starner, PharmD, BCPS; R. Scott McClelland, PharmD; Yang Qiu, MS; Richard A. Zabinski, PharmD; Nancy Cotter, PharmD; and Patrick P. Gleason, PharmD, BCPS, FCCP
To our knowledge, few studies have been published examining the impact of a PA on medical outcomes, and none have focused specifi cally on linezolid. Published evaluations of PAs have been primarily focused on proton pump inhibitors, mental health medications (antipsychotics and antidepressants), cyclooxygenase-2 inhibitors, and diabetes medications.5,20-23 Additionally, the majority of PA research only reports economic outcomes and even less reports medical costs and utilization. Moreover, study participants are most often from Medicaid or Medicare Advantage populations, making comparisons with other market segments diffi cult, and some of the research lacks a comparison population altogether.

Given the paucity of PA data with which to compare and contrast our results, we chose to compare the impact of the PA program with studies involving members that had a reversed claim for linezolid. Both a linezolid PA claim and a reversed linezolid claim could result in treatment switching and/or delays. In 2010, researchers examined the impact on healthcare utilization by Medicare Advantage patients who were recently discharged from the hospital and who had experienced reversed linezolid claims.8 The authors theorized that the high OOP linezolid costs, to which the member may be exposed, could result in treatment delays and hospital readmission. The patients with reversed linezolid claims experienced signifi cantly higher adjusted postdischarge medical expenditures ($10,594 [95% confi dence interval (CI), $8803-$12,705] vs $7953 [95% CI, $7292-$8673]) and lower adjusted postdischarge drug expenditures ($759 [95% CI, $630-$915] vs $2289 [95% CI, $2105-$2488]). The adjusted total costs were not signifi - cantly different. The impact on actual rehospitalizations, or outpatient and ED visits, was not reported. The authors noted that member cost share was the strongest predictor of claim reversal based on a propensity score model. Other research, published in poster form, also demonstrated signifi cantly higher healthcare costs in a Medicare Advantage group that was exposed to a coinsurance, resulting in OOP linezolid costs of more than $100 per claim.9 Members with reversed linezolid claims, presumably due to high OOP costs, experienced higher infection-related and 30-day allcause hospital readmissions than those without a reversal.

Our study results are in contrast to the results published by Ball et al8 and Pasquale et al.9 The linezolid PA program described in the present analysis denied linezolid insurance coverage at the point of sale, requiring prescribers to submit clinical documentation demonstrating a need for linezolid. Upon PA approval, the linezolid claim was adjudicated as a formulary agent with cost shares of $15 to $35. In the current study, member cost share was $15 to $35 in both the intervention and comparison groups and therefore likely had no impact on linezolid utilization.

Two important characteristics of this study are worth noting. First, we studied a commercial population exposed to an appropriate-use PA program, while other research was focused on member OOP linezolid costs among Medicare Advantage Plan members. Population differences could account for discrepant results, in that our average age was lower and older adult members could have been at higher risk for incurring increased costs and higher hospitalization rates. Second, it is also possible that these populations had different indications for linezolid treatment, whereas the Medicare members may have had more advanced infections. Nonetheless, the implementation of a linezolid PA was without negative medical consequences over a period of 30 and 60 days, and showed cost savings for the intervention group.


The foremost limitation of this study is its quasi-experimental design comparing 2 commercially insured populations without randomization. Although the group characteristics were similar at baseline, claims analyses are limited in their ability to account for many possible differences among individuals and prescribers. Second, the primary internal validity concern regarding the findings is the possibility of changes that may have occurred at the same time as the implementation of the PA policy, or that a sentinel effect exists affecting regional variations in health insurance coverage. We are unaware of any effects that could have changed prescribing patterns independent of the PA program at the time of the study. Third, we may have overestimated the prevalence of patients without antibiotic therapy due to the use of physician samples or cash payment for linezolid and/or other antibiotic therapy. Fourth, the study is limited in the assessment of provider costs associated with the time spent addressing the denied claim, including possibly submitting a medical exception request or providing alternate pharmacotherapy. Fifth, the generalizability of the current study fi ndings is limited to continuously enrolled, commercially insured individuals in the South and Midwest. Lastly, this study utilized administrative claims data that are used for payment purposes only and may not be representative of actual medical diagnosis or healthcare utilization.


Clinical programs aimed at appropriate use of drugs will remain a primary function of health insurers in the future. The findings of this study demonstrated a signifi cant savings associated with a linezolid PA program and failed to identify any difference in clinical outcomes between members who were or were not exposed to the linezolid PA program. Furthermore, resistance to linezolid has occurred, but it is uncommon. We still have a chance to reduce the contribution of linezolid to the growing epidemic of antibiotic resistance, and the current results would suggest we can reduce the use of linezolid without harming patient care. Future research should be directed toward studying clinical and total direct healthcare cost outcomes of utilization management programs.

Take-Away Points

Clinical programs aimed at appropriate use of drugs will remain a primary function of health insurers in the future and the findings of this study demonstrated a significant savings associated with a linezolid prior authorization (PA) program along with no difference in clinical outcomes among members who were or were not exposed to the linezolid PA program. 
  • A health plan or pharmacy benefit manager can influence appropriate linezolid use through implementation of a PA program. 

  • These results demonstrate that such a program aimed at the antibiotic linezolid could be applied without concern for an increase in negative clinical consequences. 

  • The intervention group appreciated a $0.024 per member per month antibiotic savings over a 30-day follow-up period, with both clinical and economic findings maintained at 60 days.
Author Affiliations: Prime Therapeutics LLC, Eagan, MN (CIS, YQ, RAZ, PPG); University of Minnesota, College of Pharmacy, Minneapolis, MN (CIS, PPG); Florida Blue, Jacksonville, FL (RSM, NC).

Source of Funding: None reported.

Author Disclosures: Drs Starner, Gleason, and Zabinski and Ms Qiu report employment with Prime Therapeutics, a pharmacy benefit manager. Drs McClelland and Cotter report employment with Florida Blue, a health plan.

Authorship Information: Concept and design (CIS, RSM, RAZ, NC, PPG); acquisition of data (NC); analysis and interpretation of data (CIS, RSM, RAZ); drafting of the manuscript (CIS, RSM, RAZ, NC, PPG); critical revision of the manuscript for important intellectual content (CIS, RSM, RAZ, PPG); administrative, technical, or logistic support (CIS); supervision (PPG).

Address correspondence to: Catherine I. Starner, PharmD, BCPS, Prime Therapeutics LLC, 1305 Corporate Center Dr, Eagan, MN 55121. E-mail: cstarner@primetherapeutics.com
1. Pharmacy Benefit Management Institute. 2012-2013 Prescription Drug Benefi t Cost and Plan Design Online Report. http://www.benefi tdesignreport.com/ Accessed May 23, 2013.

2. Academy of Managed Care Pharmacy. Managed Care Terms. http://amcp.org/ ManagedCareTerms. Accessed May 15, 2013.

3. MacKinnon NJ, Kumar R. Prior authorization programs: a critical review of the literature. J Manag Care Pharm. 2001;7(4):297-302.

4. Fallik B. The Academy of Managed Care Pharmacy’s concepts in managed care pharmacy: prior authorization and the formulary exception process. J Manag Care Pharm. 2005;11:358-361.

5. Shoemaker SJ, Pozniak A, Subramanian R, et al. Effect of 6 managed care pharmacy tools: a review of the literature. J Manag Care Pharm. 2010;16:S1-S20.

6. Lu CY, Soumerai SB, Ross-Degnan D, Zhang F, Adams AS. Unintended impacts of a Medicaid prior authorization policy on access to medications for bipolar illness. Med Care. 2010;48:4-9.

7. Gleason PP, Starner CI, Gunderson BW, Schafer JA, Sarran HS. Association of prescription abandonment with cost share for high-cost specialty pharmacy medications. J Manag Care Pharm. 2009;15:648-658.

8. Ball AT, Xu Y, Sanchez RJ, Shelbaya A, Deminski MC, Nau DP. Nonadherence to oral linezolid after hospitalization: a retrospective claims analysis of the incidence and consequence of claim reversals. Clin Ther. 2010;32(13):2246-2256.

9. Pasquale MK, Louder AM, Deminski MC, Chambers RB, Haider S. Out-of-pocket costs and prescription reversals: the case of oral linezolid. Poster presented at AMCP annual meeting; April 5, 2013; San Diego, CA. J Manag Care Pharm. 2013;19:182.

10. Zyvox (linezolid) prescribing information. New York, NY: Pharmacia & Upjohn Co, division of Pfi zer Inc; 2013.

11. Hicks LA, Taylor TH, Hunkler RJ. U.S. Outpatient Antibiotic Prescribing, 2010 [letter]. N Engl J Med. 2013;368(15):1461-1462.

12. Office-related antibiotic prescribing for persons aged <14 years — United States, 1993–1994 to 2007–2008. Morb Mortal Wkly Rep. 2011;60:1153-1156.

13. FDA alert: information for healthcare professionals: linezolid (marketed as Zyvox). US Food and Drug Administration website. http://www.fda.gov/Drugs/Drug-Safety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ ucm085249.htm. Accessed May 22, 2013.

14. FDA drug safety communication: updated information about the drug interaction between linezolid (Zyvox) and serotonergic psychiatric medications. US Food and Drug Administration website. http://www.fda.gov/Drugs/DrugSafety/ ucm276251.htm. Accessed May 22, 2013.

15. Ramsey TD, Lau TT, Ensom MH. Serotonergic and adrenergic drug interactions associated with linezolid: a critical review and practical management approach [published online April 2, 2013]. Ann Pharmacother. 2013;47(4):543-560. doi:10.1345/aph.1R604.

16. US Department of Health and Human Services; Centers for Disease Control and Prevention. Antibiotic resistance threats in the United States, 2013. April 23, 2013;1-114. http://www.cdc.gov/drugresistance/threat-report-2013/. Accessed November 4, 2013.

17. Charlson M, Szatrowski TP, Peterson J, Gold J. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245-1251.

18. National Cancer Institute. SEER-Medicare: Calculation of Comorbidity Weights. http://healthservices.cancer.gov/seermedicare/program/comorbidity.html.

19. DeNavas-Walt C, Proctor BD, Smith JC. US Census Bureau, Current Population Reports, P60-243, Income, Poverty, and Health Insurance Coverage in the United States: 2011. US Government Printing Offi ce, Washington, DC; 2012.

20. Starner CI, Fenrick B, Coleman J, Wickersham P, Gleason PP. Rosiglita zone prior authorization safety policy: a cohort study. J Manag Care Pharm. 2012;18: 225-233.

21. Gleason PP, Phillips J, Fenrick BA, Delgado-Riley A, Starner CI. Dalfampridine prior authorization program: a cohort study. J Manag Care Pharm. 2013;19:18-25.

22. Bergeson JG, Worley K, Louder A, Ward M, Graham J. Retrospective database analysis of the impact of prior authorization for type 2 diabetes medications on health care costs in a Medicare Advantage Prescription Drug Plan population. J Manag Care Pharm. 2013;19(5):374-384.

23. Walthour A, Seymour L, Tackett R, Perri M. Assessment of changes in utilization of health-care services after implementation of a prior authorization policy for atypical antipsychotic agents. Ann Pharmacother. 2010;44:809-817
Issue: March/April 2014
More on AJMC.COM