Modeling the Frequency and Costs Associated with Postsurgical Gastrointestinal Adverse Events for Tapentadol IR versus Oxycodone IR

Background

Few studies have estimated the economic effect of using an opioid that is associated with lower rates of gastrointestinal (GI) adverse events (AEs) than another opioid for postsurgical pain.

Objective

To estimate the number of postsurgical GI events and incremental hospital costs, including potential savings, associated with lower GI AE rates, for tapentadol immediate release (IR) versus oxycodone IR, using a literature-based calculator.

Methods

An electronic spreadsheet–based cost calculator was developed to estimate the total number of GI AEs (ie, nausea, vomiting, or constipation) and incremental costs to a hospital when using tapentadol IR 100 mg versus oxycodone IR 15 mg, in a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids for postsurgical pain. Data inputs were chosen from recently published, well-designed studies, including GI AE rates from a previously published phase 3 clinical trial of postsurgical patients who received these 2 opioids; GI event–related incremental length of stay from a large US hospital database; drug costs using wholesale acquisition costs in 2011 US dollars; and average hospitalization cost from the 2009 Healthcare Cost and Utilization Project database. The base case assumed that 5% (chosen as a conservative estimate) of patients admitted to the hospital would shift from oxycodone IR to tapentadol IR.

Results

In this hypothetical cohort of 1500 hospitalized patients, replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100-mg use predicted reductions in the total number of GI events from 1095 to 1085, and in the total cost of GI AEs from $2,978,400 to $2,949,840. This cost reduction translates to a net savings of $22,922 after factoring in drug cost. For individual GI events, the net savings were $26,491 for nausea; $12,212 for vomiting; and $7187 for constipation.

Conclusion

Using tapentadol IR in place of a traditional μ-opioid shows the potential for reduced GI events and subsequent cost-savings in the postsurgical hospital setting. In the absence of sufficient real-world data, this literature-based cost calculator may assist hospital Pharmacy & Therapeutics committees in their evaluation of the costs of opioid-related GI events.Pain is a global health problem that affects 1 of 5 adults in the community1 and occurs in 43% to 77%2–4 of the approximate 35.1 million patients who are hospitalized annually in the United States.5 Pain is ubiquitous among the nearly 30.2 million people who undergo inpatient surgery annually in the United States.5 Opioid analgesics are a mainstay of postsurgical pain management,6 but are often associated with treatment-limiting gastrointestinal (GI), central nervous system, and respiratory adverse events (AEs).7 Of these, opioid-related GI AEs are the most common,8–10 with an incidence rate of 10% to 32% for nausea and/or vomiting and 15% to 41% for constipation.7,11–14 These GI AEs are particularly troublesome after surgery, because they can exacerbate anesthesia-induced nausea and decreased GI motility, sometimes resulting in ileus.7 Furthermore, GI AEs are associated with increased healthcare resource utilization because of additional medications used to manage the GI AEs and an increase in hospital length of stay (LOS).7,10,15–17

KEY POINTS

• ▸ Opioid analgesics, a key to postsurgical pain management, are associated with lower gastrointestinal (GI) and other adverse event rates.
• ▸ Unlike traditional opioids, such as oxycodone IR, that exert analgesic activity by binding to μ-opioid receptors, tapentadol IR has a second mechanism involving norepinephrine reuptake inhibition, which may help to minimize GI events.
• ▸ Previous studies have shown that tapentadol IR causes fewer GI events than oxycodone IR in the postsurgical setting.
• ▸ This new study compared the total GI events and associated incremental costs for tapentadol IR versus oxycodone IR in the postsurgical setting from a hospital perspective, using a cost calculator and a hypothetical cohort of 1500 hospitalized patients requiring short-acting opioids.
• ▸ Replacing 5% of oxycodone IR 15-mg use with tapentadol IR 100 mg reduced the total number of postsurgical GI events from 1095 to 1085, which was associated with a cost reduction from $2,978,400 to $2,949,840.
• ▸ Individual GI event net savings for the 5% use of tapentadol IR instead of oxycodone IR were $26,491 for nausea, $12,212 for vomiting, and $7187 for constipation.
• ▸ The potential cost-savings associated with reduced GI events seen with tapentadol IR versus oxycodone IR in the postsurgical setting may suggest the need to look beyond drug-acquisition cost to consider the effect on net costs of care when making formulary decisions.

The guidelines for managing surgery-related pain advocate a multimodal, opioid-sparing approach to improve analgesic activity and to minimize the risk for opioid-related AEs.6,18 Most traditional opioids exert analgesic activity by binding to μ-opioid receptors in the brain; these receptors are also present in the GI tract. Tapentadol is a centrally acting analgesic with 2 mechanisms of action—μ-opioid receptor agonism and norepinephrine reuptake inhibition.19,20 These 2 mechanisms of action may account for the significant analgesia, along with the lower incidence and intensity of AEs that are normally associated with traditional μ-opioid receptor agonists, such as oxycodone.21In 2 phase 3 studies of patients with acute pain, including postoperative pain, the incidence of GI AEs was lower with tapentadol immediate release (IR) than with oxycodone IR at equianalgesic doses, including dose strengths other than tapentadol IR 100 mg.22,23We chose oxycodone IR as the traditional opioid because of its inclusion in guidelines for surgery-related pain,6 the availability of pivotal clinical studies comparing oxycodone IR with tapentadol IR,23,24 and its spectrum of AEs that is similar to that of tapentadol IR.23,24Although the clinical benefits of using opioids with different mechanisms of action are well documented, few studies have examined the potential economic effect of this strategy in postsurgical populations.The objective of this study was to estimate the number of potential reductions in postsurgical GI AEs and incremental hospital costs for GI event rates associated with tapentadol IR versus oxycodone IR, using a literature-based calculator. The analysis focused on data related to postsurgical GI AE rates, because of their availability in the published literature.