Background    This Fast Fact reviews controlled release oxycodone (CRO) usage in palliative care.

Indication    CRO is indicated for moderate to severe pain requiring continuous, around-the-clock analgesia for an extended period in patients ≥ 18 years of age.  CRO is FDA approved in opioid-tolerant pediatric patients over 11 years old (1).

Pharmacology    Oxycodone is a semi-synthetic opioid that interacts with both mu- and kappa-opioid receptors. Patients typically experience analgesia starting an hour after taking a CRO dose, and Tmax occurs around 4-h (2,3). Oxycodone is metabolized in the liver to active metabolites that are renally excreted and so should be used with caution in patients with renal and/or liver impairment. Oxycodone and its metabolites are removed by hemodialysis (unlike morphine) (4,5), however opioids which are mostly liver-metabolized are preferred drugs for patients on hemodialysis (methadone, buprenorphine, fentanyl). Head-to-head studies with other opioids (mostly morphine) suggest that oxycodone’s side effects are of similar magnitude to other commonly used opioid analgesics (6).

Efficacy     CRO has been extensively studied in cancer pain, showing its efficacy is similar to other commonly used opioids (6).

Euphoria, addiction-risk, and abuse-deterrent formulations   CRO played a uniquely important role in the opioid overdose epidemic in the US starting in the 2000s (7). This was due to many factors, including illegal & misleading marketing of CRO as “safe” and its widespread availability to be diverted for non-medical use. Additionally, there are data to suggest that oxycodone is more euphorigenic/rewarding than other commonly used opioids and it is believed that oxycodone is more addictive than other commonly prescribed opioid analgesics (8). This may be due to oxycodone’s strong kappa-opioid receptor agonism which is unique amongst commonly prescribed opioids (9). In response to CRO’s role in the opioid overdose epidemic, all currently available CRO products in the US are ‘abuse-deterrent.’ These formulations make it difficult for users to crush/dissolve CRO products such that they can be inhaled or injected. Note: patients can still experience euphoria, sedation, fatal overdose, or develop opioid use disorder using unaltered, swallowed abuse-deterrent CRO products. However, there are modest data showing both currently available abuse-deterrent formulations reduce the risk of overdose (8).  

• OxyContinTM: OxyContin was re-formulated in the 2010s to be abuse-deterrent. If crushed it forms a viscous gel that cannot be injected and is difficult to administer nasally. OxyContin is available in pill strengths of 10, 15, 20, 30, 40, 60, 80 mg.
• Xtampza ERTM is a capsule containing abuse-deterrent oxycodone microspheres that dissolve slowly in the gut and clump & gel if crushed. Xtampza ER capsules can be safely opened and taken orally with soft foods for patients with dysphagia or suspended in water and flushed down a gastrostomy tube. Xtampza ER capsules come as 9, 13.5, 18, 27, 36 mg. While not bioequivalent, for most patients the analgesic strength of an Xtampza ER capsule will be like its closest OxyContin pill strength (e.g. 27 mg of Xtampza ER is similar in strength to 30 mg OxyContin).

Equianalgesic Information    Studies comparing round the clock immediate-release oxycodone to CRO products demonstrate equivalent results. The conversion factor between morphine and oxycodone has been controversial, but the most accepted data suggests that 30 mg of oral morphine is equivalent to 20 mg of oxycodone.  Since all equianalgesic values are rough guidelines, prescribers need to use their clinical judgment in determining the most appropriate starting dose (see Fast Fact #36).

Dosage    The starting dose of CRO in an opioid naïve patient is 10 mg q12 hours; it can be dose escalated every 24-48 hours (see Fast Fact #20). For opioid-tolerant patients, the starting dose should be determined using standard opioid-conversion dosing strategies (see Fast Fact #36). A substantial minority of patients will experience end-of-dose failure of a CRO dose by about 10 hours and require q8h dosing. CRO is not approved for rectal administration.

Cost    CRO remains one of the most expensive extended-release opioids on the market. There are currently no generic CRO product on the market.

Summary    CRO is an effective long-acting oral opioid for cancer pain. Due to its increased risks (of developing dependency and OUD) and costs, it is not a first-line agent compared with other extended-release opioids. There are no data that CRO offers any analgesic benefit compared to other opioids.  

References 

1. Hain R, Miser A, Devins, et al.  Strong opioids in pediatric palliative medicine.  Pediatr Drugs. 2005; 7:1-9.
2. OxyContin Prescribing Information. US Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/022272s027lbl.pdf. Accessed April 21, 2025.
3. Xtampza ER Prescribing Information. US Food and Drug Administration. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208090s000lbl.pdf. Available April 21, 2025.
4. Odoma VA, Pitliya A, AlEdani E, et al. Opioid prescription in patients with chronic kidney disease: a systematic review of comparing safety and efficacy of opioid use in chronic kidney disease patients. Cureus. 2023;15(9):e45485.
5. Coluzzi F, Caputi FF, Billeci D, et al. Safe use of opioids in chronic kidney disease and hemodialysis patients: tips and tricks for non-pain specialists. Ther Clin Risk Manag. 2020;16:821-837.
6. Schmidt-Hansen M, Bennett MI, Arnold S, et al. Oxycodone for cancer-related pain. Cochrane Database Syst Rev. 2022;6(6):CD003870.
7. Gadd S, Cox N, Samuelson J, Kenney A, Turner K, Cochran G. Abuse-deterrent opioid formulations and the opioid crisis: a pharmacist’s perspective. Therapeutic Drug Monitoring. 2021;43(1):35-41.
8. Wightman R, Perrone J, Portelli I, Nelson L. Likeability and abuse liability of commonly prescribed opioids. J Med Toxicol. 2012;8(4):335-340.
9. Kibaly C, Alderete JA, Liu SH, et al. Oxycodone in the opioid epidemic: high “liking”, “wanting”, and abuse liability. Cell Mol Neurobiol. 2021;41(5):899-926.

Version History:  This Fast Fact was originally edited by David E Weissman MD. 2nd Edition was edited by Drew A Rosielle MD and published October 2007; 3rd Edition was edited by Sam Maiser MD in June 2015; 4th Edition by Drew A Rosielle MD and was published in May 2025.
Conflicts of Interest: None to disclose.