Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone

Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown. This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients.

A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015-2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records.

After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91-1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45-1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86-2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06-1.50), but not to the same extent.

Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.