Oxycodone and a Useful Book

Opioids are the backbone of the management of moderate to severe pain as defined by the World Health Organization ladder. In most patients, morphine is the favored drug, however, in some the intolerable side effects and lack of efficacy dictates the use of another opioid, such as oxycodone. Oxycodone is a semisynthetic derivative of thebaine, an opium alkaloid, and can also be made by modifying morphine. It has the same structural relationship to codeine that oxymorphone has to morphine and is a potent opioid mu-receptor agonist. Oxycodone is 10 times as potent as codeine and is demethylated and conjugated in the liver. It is excreted in the urine with part of its analgesic effect mediated by active metabolites. The half-life is 2 to 3 hours and the duration of action is 4 to 5 hours. Oxycodone is at least half as potent orally as administered parenterally, so it is usually given orally. In a study of 20 patients, Glare and Walsh found single-entity oxycodone to be equianalgesic with morphine when using the oral route during chronic administration for cancer pain. Oxycodone has been used clinically since 1917, with varying patterns of use worldwide. The annual use of oxycodone has increased 42-fold in the United Kingdom and 3-fold in the United States from 1999 to 2003. It is widely used in the United States in a low dose combined with a nonopioid analgesic drug. The formulation is usually given as a tablet containing 5 mg oxycodone in a fixed combination with a nonopioid analgesic such as acetaminophen (Percocet, Endocet, Tylox) or aspirin (Percodan, Endodan) to name a few examples. It is considered a weak opioid analgesic because the dose cannot be increased above 10 mg every 4 hours due to the risk of liver damage from acetaminophen or gastrointestinal distress from aspirin. However, based on their study, Glare and Walsh have advocated that single-entity oxycodone be reclassified as a strong opioid analgesic. In a follow up to the initial study, Glare and Walsh studied 24 patients with advanced cancer and chronic pain who were treated with oxycodone every 4 hours. Of the 24 patients, 20 completed the study. The median starting dose was 15 mg (range of 5 to 30 mg) and of the 20 patients who completed the study, the median stable dose was 20 mg (range of 15 to 60 mg). Although not statistically significant, patients less than 65 years had a higher median stable dose, that is, 45 mg versus 20 mg for the older patients. Side effects were mild, commonly being sedation, constipation, and nausea/vomiting. Pain relief was achieved with doses up to 60 mg every 4 hours and was the preferred analgesic in the vast majority of the patients. Several interesting observations were made by the authors from this study. First, the effective doses of oxycodone were similar to oral morphine with most patients experiencing pain relief at a dose of 30 mg every 4 hours or less. Second, patients older than 65 years required less oxycodone, which is like the pharmacokinetics of morphine where patients older than 50 years have significantly higher plasma levels than those younger than 50 years given the same single doses. Third, the side effects of oxycodone did not differ from other opioids. Finally, the authors concluded that oral oxycodone was versatile, flexible, and provided durable analgesia in patients with advanced cancer and chronic pain much like oral morphine. In a more recent study, Reid et al reported the results of a meta-analysis of randomized controlled trials on the use of oxycodone for cancer-related pain. Four studies comparing oral oxycodone to either oral morphine or oral hydromorphone were ultimately identified and analyzed. The study found no differences between analgesic efficacy or the adverse side effect profile of oxycodone compared to morphine, again, confirming the use of oxycodone for cancer-related pain. In this issue of the Journal, Mercadante et al report the results of their study of the use of high dose oxycodone in an acute palliative care unit. The reader is encouraged to read the entire article, but this study confirms the previous findings that oxycodone, including the controlled release formulation, is safe and as effective as morphine in the treatment of chronic pain and that doses were significantly lower in older patients. So, after the above review of the use of oxycodone rather than morphine for the treatment of chronic pain, what is the equianalgesic ratio of the 2 drugs? Cannot remember? Do not know where to look? Well, a good source for this answer is the just published book entitled Demystifying Opioid Conversion Calculations. A Guide for Effective Dosing by Mary Lynn McPherson. Dr McPherson is Professor and Vice Chair,