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 prolongedrelease 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. Case 2A 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 controlledrelease 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. Case 3A 51-year-old man with a sacral chondrosarcoma and poorly controlled pain became narcotised (lifethreatening 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. 2017;40:156-7 https://doi.org/10.18773/ austprescr.2017.018 Alicia Ward Consultant Michaela del Campo Pharmacist Kathy HauserConsultant Central Adelaide Palliative Care Services Adelaide Aust Prescr CommentThe combination of prolonged-release oxycodone with naloxone is marketed to reduce pain and opioidinduced constipation. Naloxone aims to counteract the effect of oxycodone on the gut over 12 hours as it antagonises opioid receptors in the gastrointestinal tract. As naloxone then undergoes extensive first-pass metabolism in the liver, insignificant amounts enter the systemic circulation. In healthy people its bioavailability is less than 3%. The combination is contraindicated in moderate-severe liver dysfunction (Child-Pugh B-C).We have observed prescription of higher than recommended doses and the commencement or continuation of prolonged-release oxycodone with naloxone despite deteriorating liver function. This needs to be avoided. If a patient with liver impairment is changed from oxycodone with naloxone to a single opioid formulation, start with a lower equivale...
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