Exposure to Potential CYP450 Pharmacokinetic Drug–Drug Interactions among Osteoarthritis Patients: Incremental Risk of Multiple Prescriptions

Abstract

Abstract: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 Address correspondence and reprint requests to: Joseph V. Pergolizzi

Economic impact of potential drug–drug interactions in opioid analgesics

“…While the global incidence of PK DDIs is not known, a sharp increase in such DDIs was noted among seniors from 1992 to 2005, with a prevalence of 19.2% in patients 70 years of age 16 . Previous research found a 27% prevalence of DDEs with the potential to cause PK DDIs among ambulatory chronic low back pain patients using CYP450 opioid analgesics 17 and 26% in osteoarthritis 18 .…”

The Prevalence of Opioid-Related Major Potential Drug-Drug Interactions and Their Impact on Health Care Costs in Chronic Pain Patients

“…In addition, we further improved upon previous work by controlling for exposure to various precipitant/concomitant drugs in the 90-day observation these studies, the exposure of patients with chronic low back pain and osteoarthritis treated with opioids to potential pDDIs was approximately 30%. 16,17 In patients with osteoarthritis taking a CYP450 metabolized opioid, the risk of exposure to a potentially interacting drug was higher in females and increased with age and the number of medications at baseline before receiving an opioid. 18 These data are in agreement with our current results and suggest that many chronic users of opioids are at high risk for potential pDDIs.…”

“…16,17,20,21 These studies comparing costs of exposures, regardless of the clinical importance, could have confounding effects and potentially result in improper estimation of the impact of pDDIs on health care costs. To mitigate this potential, the current study used strict inclusion criteria to focus on patients expected to be most affected by pDDIs (pDDI-Major) as well as obtain patient cohorts that were very similar in terms of baseline characteristics.…”

“…15 Previous research has reported a 27% prevalence of pDDIs among ambulatory chronic low back pain patients using CYP450 opioid analgesics and 26% in patients with osteoarthritis. 16,17 Among patients using opioids, regardless of diagnosis, the mean 6-month health care costs after pDDIs were significantly higher versus matched patients without pDDIs (difference of $667). 18 Thus, pDDIs seem to lead to side effects that incur increased health care costs.…”

“…19 Some studies have been published on the topic of CYP450 related pDDIs between opioids and precipitant drugs. [16][17][18][19][20][21] However, one major limitation associated with these studies was that the pDDI was simply defined as a concurrent exposure between an opioid metabolized through the CYP450 system and a precipitant drug (inducer or inhibitor), which was also metabolized through the CYP450 system.…”