Exposure to potential CYP450 pharmacokinetic drug-drug interactions among osteoarthritis patients: incremental risk of multiple prescriptions

Pain Pract. 2011 Jul-Aug;11(4):325-36. doi: 10.1111/j.1533-2500.2010.00438.x. Epub 2010 Dec 28.


Patients taking more than one drug metabolized through the cytochrome P450 (CYP450) enzyme system experience a drug-drug exposure (DDE), which puts them at risk for a potential pharmacokinetic drug-drug interaction (DDI), defined as two or more drugs interacting in such a way that the effectiveness and/or toxicity of one or all drugs are changed. Any patient subjected to a DDE is at risk for a potentially serious DDI, the epidemiology of which has not been thoroughly studied. Many drugs are metabolized primarily via the CYP450 enzyme system, including certain opioids used to manage moderate to severe chronic pain. We conducted a retrospective analysis of a large commercial claims database and a Medicare database to assess the prevalence of DDEs among patients with osteoarthritis taking CYP450-metabolized opioids. The overall prevalence of DDEs in this population was 26%, with females more likely to experience DDEs than males (28.4% vs. 21.0%, respectively). The number of unique concurrent prescriptions at baseline, gender, age, and Charlson Comorbidity Index were statistically significant predictors of DDEs (P < 0.05). This study challenged previous assumptions about DDEs in that advanced age was not positively associated with the risk of DDE. However, the number of prescriptions the patient received in the 90-day window prior to the index date was a risk factor. For patients taking at least two medications in the 90-day period prior to the index date, every additional prescription taken increased their risk for a DDE during the observation period by 138% (on average). The risk of DDE during the study period was threefold greater for patients with one medication in the 90-day period before index date compared with similar patients with no prescriptions in that same period before the index date. DDEs are more common than may be generally believed in patients with osteoarthritis, regardless of age, and can occur even in patients taking few medications. When selecting an opioid analgesic to treat osteoarthritis, physicians should consider the potential for exposure of these patients to drugs that could interact unfavorably.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cytochrome P-450 Enzyme System / metabolism*
  • Databases, Factual
  • Drug Interactions
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoarthritis / drug therapy*
  • Osteoarthritis / metabolism
  • Polypharmacy*
  • Retrospective Studies
  • Sex Factors


  • Cytochrome P-450 Enzyme System