Out-of-Pocket Costs and Prescription Reversals With Oral Linezolid

Published Online: September 18, 2013
Margaret K. Pasquale, PhD; Anthony M. Louder, PhD, RPh; Michael C. Deminski, MS, RPh; Richard B. Chambers, MSPH; and Seema Haider, MSc
Objective: To determine the relationship between benefit design, out-of-pocket costs, and prescription reversals, and the impact of reversals on rehospitalizations and total healthcare costs among Medicare members prescribed oral linezolid.

Study Design: Medicare members from a national health plan prescribed oral linezolid posthospitalization for skin and soft tissue infection (SSTI) or pneumonia were followed retrospectively.

Methods: Members were identified by an oral linezolid prescription between June 1, 2007, and April 30, 2011, where the index event was a prescription fill or reversal less than 2 days before or 10 days after discharge. Associations between out-of-pocket costs and reversal, and between reversal and rehospitalization 30 days postindex, were compared for prescription fills versus reversals. A generalized linear model calculated adjusted total healthcare costs per member controlling for age, sex, geographic region, and clinical characteristics.

Results: Reversal rates rose progressively from 2% for members with out-of-pocket costs of $0 to 27% for members with out-of-pocket costs higher than $100 (P <.0001). Infection-related rehospitalizations were 23% versus 9% for members with a  prescription reversal versus a fill (P <.0001). While postdischarge prescription drug costs were $1228.78 lower (P <.0001), adjusted mean medical costs were $2061.69 higher (P = .0033) and total healthcare costs were $1280.93 higher (P = .0349) for reversal versus fill members.

Conclusions: Higher out-of-pocket costs were associated with higher rates of reversal, and reversals were associated with higher rates of rehospitalization and adjusted total healthcare costs among Medicare members prescribed oral linezolid posthospitalization for SSTI or pneumonia.

Am J Manag Care. 2013;19(9):734-740
High out-of-pocket costs (coinsurance rather than copay) were associated with prescription reversals among Medicare members prescribed oral linezolid after hospitalization for an uncomplicated or complicated skin infection or pneumonia. Also, members with prescription reversals experienced higher rates of rehospitalization and higher total healthcare costs than members with prescription fills.
  • Reversal rates rose from 2% for out-of-pocket costs of $0 to 27% for out-of-pocket costs of more than $100.

  • Infection-related rehospitalizations were 23% for reversal members versus 9% for fill members.

  • Adjusted mean postdischarge healthcare costs were $1280.93 higher for members with reversals than for fill members.
Linezolid is indicated for the treatment of vancomycin-resistant Enterococcus faecium infections, complicated and uncomplicated skin and soft tissue infections (SSTIs), and nosocomial and community-acquired pneumonia (eAppendix available at www.ajmc.com).1 Pathogens for such infections include Staphylococcus aureus (methicillin-susceptible and resistant strains), Streptococcus pneumoniae (including multidrug-resistant strains), Streptococcus pyogenes, and Streptococcus agalactiae. Among these, methicillin-resistant Staphylococcus aureus (MRSA) infections have received particular  attention in the 2000s commensurate with evidence indicating a dramatic rise in the rate of MRSA-related hospital admissions.2-4 Whereas more recent studies suggest community-onset and hospital-onset MRSA infections may have tapered and declined somewhat since 2005,5,6 the burden of SSTIs overall remains substantial, and if these infections are not appropriately treated they can result in serious life-threatening consequences.

Among antibiotics used to treat SSTIs and pneumonia, linezolid is available in both intravenous and oral forms. Oral  bioavailability is approximately 100%,1 allowing for sequential intravenous to oral administration without changing the drug or dosing regimen. The availability of intravenous and oral forms may allow for a shortened length of hospital stay if treatment is continued orally after discharge, resulting in lower total costs of treating the infection.7 However, due to oral linezolid’s high out-of-pocket costs, patients have been known to decline purchase of (reversals) their prescriptions and receive treatment with an alternative antibiotic or forgo treatment altogether.8

Previous research by Ball and colleagues7 based on Humana Inc health plan members examined whether rehospitalization rates and total healthcare costs increased for members with a prescription reversal versus a fill of oral linezolid. Although members with a claim reversal were rehospitalized at higher rates and had higher medical costs compared with those who had a fill, they did not have higher total healthcare costs than members with a prescription fill for oral linezolid. This implied that oral linezolid and  alternative antibiotics or the absence of treatment were similarly cost-effective. However, one limitation of the study by Ball and colleagues was that diagnosis for the initial hospitalization was not confirmed for an infection indicated for linezolid treatment. A second limitation of the study by Ball and colleagues was that members were followed for as long as 60 days postdischarge, which potentially led to inclusion of healthcare utilization and costs unrelated to the initial infection and its consequences.

This research sought to refine the study by Ball and colleagues by restricting the identification of members to those whose initial hospitalization was for complicated or uncomplicated SSTI or pneumonia diagnoses (eAppendix), as well as shortening the postdischarge time period to 30 days to examine acute consequences more likely related to the initial hospitalization. Members from both commercial and Medicare lines of business were initially identified for the study, but all analyses were conducted separately by line of business because of significant differences in plan reimbursement. This study focuses on the Medicare line of business, which comprised a majority (71%) of the total membership.


Study Data

This study utilized data from Humana’s SAS database which contains enrollment, medical, and pharmacy claims data for Humana’s Medicare membership. All data sources were merged using de-identified member data. The finalized protocol was approved by a central independent institutional review board.

Study Design

We performed a retrospective cohort analysis of all Medicare members identified as having a prescription claim for oral linezolid after discharge from an inpatient stay for complicated  or uncomplicated SSTI or pneumonia (eAppendix).Members were identified during the time period of June 1, 2007, to April 30, 2011. The service date of the first linezolid prescription claim was  used to identify the date of the index event (fill or reversal). Members who were identified with a reversal in the pharmacy claims  but who filled the prescription for oral linezolid within 3 days after the reversal were recategorized as fill members. Members with a claim reversal were compared with those without a reversal in terms of plan design (whether members paid a copay or had coinsurance), member out-of-pocket costs, infection-related (complicated or uncomplicated SSTI or pneumonia) and all-cause rehospitalization (inpatient admission with overnight stay), and healthcare costs (prescription, medical, and total) in  the 30 days post discharge.

Study Population

Study subjects were fully insured Medicare Advantage members aged 18 to 89 years who were continuously enrolled for 120 days before and 30 days after the index event (linezolid  fill or reversal) and whose index linezolid claim was processed no more than 2 days before or 10 days after hospital discharge. A diagnosis of complicated or uncomplicated SSTI or pneumonia in any position on the inpatient claim was required for the initial hospitalization.

Members were excluded from analysis if they were enrolled as administrative services–only populations (members of  employer-funded plans excluded by contract from research), had a claim for pregnancy (International Classification of  Diseases, Ninth Revision codes 630.xx-679.xx, V22.xx, and V23.xx), or were in a skilled nursing facility/nursing home any time during the study period.

Statistical Analysis

Claims data for Medicare members prescribed oral linezolid and discharged from an inpatient stay for complicated or uncomplicated SSTI or pneumonia were examined for benefit design, out-of-pocket costs, reversals, rehospitalizations, and healthcare costs. Visual inspection was used to distinguish between copay and coinsurance because the medical claims did not contain an explicit indicator for copay or coinsurance. All integer values (ie, $6, $10, $25, $30, $100, $150) and known noninteger values of Medicare Part D copays (ie, $5.60, $6.30) were classified as copay, while all remaining noninteger values (ie, $57.43, $238.59) were classified as coinsurance. For all descriptive analyses, means were compared using 2-sample t tests and count variables were compared using x2 tests. Demographic and clinical characteristics included age, sex, geographic region, low-income status and dual eligibility (Medicare and Medicaid eligibility), characteristics of the initial broader window typically necessary for medical claims–based comorbidity scores such as the Charlson Comorbidity Index score.14

The impact of the reversal on postindex healthcare costs (plan payment plus member medical cost) was modeled using a generalized linear model (GLM) with a gamma distribution as its probability distribution and log link as its link function. Generalized linear models are commonly utilized to account for distributions of highly skewed data, characteristic of medical expenditures.15 The log link function for the GLM is specified below, where μ refers to postindex healthcare costs:

log u = reversal + Out-of-PocketCategory + age

+ gender + region + LowIncomeSubsidy-DualEligible

+ RxRiskV + ICUstay + surgery + pre-indexhealth

care costs

Covariates included in the model were age, sex, geographic region, low-income subsidy/dual eligibility, baseline RxRisk-V score, a surgical procedure or an intensive care unithospitalization such as surgery or intensive care unit stay, and the RxRisk-V comorbidity score, a surgical procedure or an intensive care unit stay during the initial hospitalization, out-of-pocket costs, and preindex healthcare costs (per $1000). In order to include data on members with no costs during the follow-up period, $1 was added to all member costs. The models provided adjusted mean costs and 95% confidence intervals for the prescription fill and reversal groups.


A total 1062 Medicare members were available for analysis. Among the total sample, 16.5% of the members reversed their prescription for oral linezolid. Demographic and clinical characteristics by fill versus reversal groups indicated there were no statistical differences in age, sex, or geographic region (Table 1). However, a higher percentage of the members filling their linezolid prescription had low-income subsidy/ dual-eligibility status compared with members reversing their linezolid prescription (P <.0001). A majority of the characteristics of the initial hospitalization were similar, with the exception that a statistically higher percentage of reversal members were hospitalized for complicated or uncomplicated SSTI (P = .0148). That corresponded to a higher percentage of fill members hospitalized for pneumonia (P = .0106). The RxRisk-V comorbidity scores and preindex total healthcare costs were not statistically different between the 2 groups.

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