A 43-year-old woman with metastatic breast cancer was admitted with constipation. She had liver metastases, ascites and impaired synthetic function (Child-Pugh B),1 but aspartate aminotransferase and alanine aminotransferase were within normal limits.
Her analgesia was changed from sustained-release morphine to a combination product of prolonged-release oxycodone with naloxone. Within two hours of the first dose she developed severe pain. This was uncontrolled by morphine and ketamine infusion.
The pain persisted for 12 hours after receiving the prolonged-release oxycodone with naloxone. The patient was recommenced on her previous morphine regimen and achieved ongoing stable pain control.
A 50-year-old man with metastatic prostate cancer had increasing pain despite increasing doses of prolonged-release oxycodone with naloxone (up to 40/20 mg twice daily) plus controlled-release oxycodone (10 mg twice daily). The man reported no effect from using immediate-release oxycodone for breakthrough pain. He had liver metastases but aspartate aminotransferase and alanine aminotransferase were within normal limits (Child Pugh A).
The prolonged-release oxycodone with naloxone was ceased and controlled-release oxycodone 20 mg twice daily was commenced (a significantly lower opioid dose). Within two days, the patient’s pain and functional status greatly improved enabling his cancer therapy to be resumed.
A 51-year-old man with a sacral chondrosarcoma and poorly controlled pain became narcotised (life-threatening overdose) when prolonged-release oxycodone with naloxone was ceased while on a stable dose of methadone. Once the methadone was cleared over the next few days his analgesia was significantly improved on a comparatively lower dose morphine infusion (without the multiple adjuvant analgesics previously required). He had no liver metastases, normal aspartate aminotransferase and alanine aminotransferase (Child-Pugh A) with fatty liver on ultrasound.
- not using prolonged-release oxycodone with naloxone if there is any degree of liver dysfunction as there is a risk of poor analgesia or withdrawal
- avoiding prolonged-release oxycodone with naloxone in combination with other long-acting opioids, especially methadone
- further research to understand how to safely cease or rotate the prolonged-release oxycodone with naloxone when prescribed alone or with other opioids to reduce the risk of opioid toxicity.
Conflicts of interest: none declared
- Sloss A, Kubler P. Prescribing in liver disease. Aust Prescr 2009;32:32-5.
- Pain: opioid therapy in palliative care. In: eTG complete [Internet]. Melbourne: Therapeutic Guidelines Limited; 2017. [cited 2017 Jul 1]
- Gelston EA, Coller J, Lopatko O, James H, Schmidt H, White J, et al. Methadone inhibits CYP2D6 and UGT2B7/2B4 in vivo: a study using codeine in methadone- and buprenorphine-maintained subjects. Br J Clin Pharmacol 2012;73:786-94.
- Burns E, McWilliams K, Ross C. A cautionary tale of oral naloxone. J Pain Symptom Manage 2014;47:e1-e2.
- Kang JH, Lee GW, Shin SH, Bruera E. Opioid withdrawal syndrome after treatment with low-dose extended-release oxycodone and naloxone in a gastric cancer patient with portal vein thrombosis. J Pain Symptom Manage 2013;46:e15-7.
- Mercadante S, Ferrera P, Adile C. High doses of oxycodone-naloxone combination may provide poor analgesia. Support Care Cancer 2011;19:1471-2.