The opioids hydrocodone and oxycodone, both schedule II drugs since 2014 recognized to have a high potential for misuse, are commonly prescribed for strong short-term pain, such as from an injury or surgery, and long-term pain, such as from a chronic cough, cancer, or arthritis. Both hydrocodone and oxycodone can be taken alone or in combination with other drugs. As the opioid epidemic continues to kill up to 70,000 individuals on average annually 1, with both hydrocodone and oxycodone contributing to the issue 2, their associated risks remain an important area of active investigation.
In general, oxycodone has been theorized to have heightened misuse risks due to its greater likability scores and minimal negative subjective effects as compared to hydrocodone and morphine 3. However, a study of commercially insured patients identified that the probability of long-term use following a first prescription was 5.1% for short-acting hydrocodone, in contrast to 4.7% for short-acting oxycodone. Short-acting hydrocodone and oxycodone were both associated with a lower risk of long-term use compared to long-acting opioids and other schedule II short-acting opioids 4.
Most recently, a large retrospective analysis of multiple Oregon-based public health datasets sought to assess the risk of opioid-related adverse events, in the form of either an opioid overdose or chronic use, following a first prescription of hydrocodone or oxycodone to opioid naïve patients 5. Overall, data revealed that nearly 3% of individuals developed chronic opioid use and 0.3% experienced an overdose.
After adjusting for patient and initial prescription characteristics, patients receiving hydrocodone experienced a higher risk of developing chronic use than did patients receiving oxycodone. Meanwhile, patients receiving oxycodone, either alone or in combination with acetaminophen, experienced a higher risk of overdose. An overdose may represent the most dangerous outcome following the initiation of opioid therapy. Research has identified older patients and individuals affected by multiple medical comorbidities or certain psychiatric conditions as being the most vulnerable to overdose 6.
As such, data suggested that oxycodone monotherapy strongly increases the risk of opioid overdose as compared to hydrocodone. As such, in order to reduce overdose-related deaths, hydrocodone may need to be favored, despite having a higher rate of chronic use.
However, this study was limited in a number of respects. First, the data analysis was carried out in a retrospective way and based upon a dataset created for administrative purposes which may have overlooked key clinical nuances. Second, up to half of the ethnicity data had to be imputed, compromising the accuracy of any race and ethnicity-related findings. Third, the data did not control for the indication of the first prescription, such as major surgery, an injury, or a chronic illness. This may have compromised the applicability of the findings to all clinical contexts.
When comparing the side effects of the two drugs, research shows that hydrocodone and oxycodone result in similar negative side effects. These include depressed respiration, drowsiness, nausea and vomiting, lethargy, a dry mouth, itching, and impaired motor skills 7.
In addition, oxycodone is more likely to incur side effects such as dizziness and drowsiness, alongside headaches and fatigue, while hydrocodone is more likely to cause constipation and stomach pain. Severe side effects of hydrocodone, though less common, also include seizures, tachycardia, painful urination, and patient confusion.
Additional unbiased research thoroughly controlling for any confounding factors is warranted to elucidate the relative risks associated with the use of hydrocodone vs. oxycodone in order to determine the safest use of opioids for pain relief. Meanwhile, a thorough analysis of their risks and benefits will need to be carried out to inform their use in a patient-specific context.
References
1. About the Epidemic | HHS.gov. Available at: https://www.hhs.gov/opioids/about-the-epidemic/index.html.
2. Cicero, T. J., Ellis, M. S., Surratt, H. L. & Kurtz, S. P. Factors influencing the selection of hydrocodone and oxycodone as primary opioids in substance abusers seeking treatment in the United States. Pain (2013). doi:10.1016/j.pain.2013.07.025
3. Wightman, R., Perrone, J., Portelli, I. & Nelson, L. Likeability and Abuse Liability of Commonly Prescribed Opioids. J. Med. Toxicol. (2012). doi:10.1007/s13181-012-0263-x
4. Shah, A., Hayes, C. J. & Martin, B. C. Characteristics of Initial Prescription Episodes and Likelihood of Long-Term Opioid Use — United States, 2006–2015. MMWR. Morb. Mortal. Wkly. Rep. (2017). doi:10.15585/mmwr.mm6610a1
5. Weiner, S. G. et al. Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone. PLoS One 17, e0266561 (2022). doi: 10.1371/journal.pone.0266561.
6. Weiner, S. G. et al. Factors Associated with Opioid Overdose after an Initial Opioid Prescription. JAMA Netw. Open (2022). doi:10.1001/jamanetworkopen.2021.45691
7. Oxycodone vs. Hydrocodone for Pain Relief. Available at: https://www.healthline.com/health/pain-relief/oxycodone-vs-hydrocodone#side-effects.