The prevalence of opioid-related major potential drug-drug interactions and their impact on health care costs in chronic pain patients

J Manag Care Spec Pharm. 2014 May;20(5):467-76. doi: 10.18553/jmcp.2014.20.5.467.


Background: Literature has shown that chronic pain patients prescribed opioids are at an increased risk for experiencing drug-drug interactions as a result of polypharmacy. In addition, chronic, noncancer pain patients who experience drug-drug interactions have been shown to have greater health care utilization and costs. However, no study has focused on the health economics of major clinically significant drug-drug interactions associated with long-acting opioids.

Objectives: To (a) estimate the prevalence of major drug-drug interactions among patients prescribed a long-acting opioid and (b) evaluate the potential impact of major drug-drug interactions on health care costs.

Methods: This study was a retrospective cohort analysis using claims data from the MarketScan Commercial Claims and Encounter Database between 2008 and 2010. Patients with at least 1 prescription for a long-acting opioid for ≥ 30 days were placed into cohorts according to the expected clinical impact of the potential drug-drug interaction: major versus none. Propensity score matching was used to mitigate differences in baseline characteristics between the cohorts. Health care costs were based on payments for all covered health care services, which consisted of inpatient and outpatient medical, emergency department, and outpatient prescription costs.

Results: Among 57,752 chronic, noncancer pain patients who met all inclusion and exclusion criteria, 5.7% (3,302) were exposed to a potential major drug-drug interaction. The costs associated with a potential interaction versus no potential interaction were significantly more after baseline characteristics of the cohorts were normalized by propensity score matching. Monthly health care costs in the 90-day post-index period were significantly greater ($3,366 vs. $2,757, a $609 difference) in patients exposed to a potential drug-drug interaction of major clinical significance, compared with those not exposed to a drug-drug interaction. The higher health care costs were mainly driven by outpatient and inpatient medical costs.

Conclusions: Exposure to potential drug-drug interactions may result in unnecessary and unintended health care costs. Physicians should be made aware of commonly administered cytochrome P450 (CYP450) metabolized drugs in the chronic pain patient and consider prescribing non-CYP450 metabolized opioid and nonopioid analgesics. Managed care's use of utilization management tools to avoid these exposures may reduce costs.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / economics
  • Analgesics, Opioid / pharmacokinetics
  • Biotransformation
  • Chi-Square Distribution
  • Chronic Pain / diagnosis
  • Chronic Pain / drug therapy*
  • Chronic Pain / economics*
  • Chronic Pain / epidemiology
  • Cost Savings
  • Cytochrome P-450 Enzyme Inhibitors / adverse effects
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Costs
  • Drug Interactions*
  • Health Care Costs*
  • Humans
  • Least-Squares Analysis
  • Linear Models
  • Managed Care Programs / economics*
  • Multivariate Analysis
  • Polypharmacy
  • Prevalence
  • Propensity Score
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • United States / epidemiology


  • Analgesics, Opioid
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System