Use of Hydromorphone, with Particular Reference to the OROS® Formulation, in the Elderly

Abstract

The prevalence of pain increases with age. However, pain is often inadequately managed in elderly people, which undermines quality of life. Pain has been associated with depression, sleep disturbances, impaired ambulation, and increased healthcare use and costs. Effective treatment of pain improves the overall quality of life. However, pain management is complicated by the presence of multiple co-morbidities in elderly people, which increases the likelihood of polypharmacy, and therefore increases the chance of potential drug-drug interactions. Polypharmacy is also associated with poor adherence to therapy. Age-related pharmacokinetic and pharmacodynamic changes reduce the therapeutic index of drugs. Therefore, elderly people are more likely to suffer from adverse events and increased sensitivity to the analgesic properties of opioids. OROS hydromorphone (Jurnista) is a once-daily, extended-release formulation that uses the OROS push-pull technology to provide controlled release of the semi-synthetic opioid hydromorphone. Compared with conventional immediate-release hydromorphone, OROS hydromorphone provides more consistent delivery of hydromorphone with lower peak concentrations and less variability in plasma concentrations over time. The bioavailability of hydromorphone from OROS hydromorphone is minimally affected by food or alcohol (ethanol). Hydromorphone is mainly metabolized in the liver and is excreted in the urine. Unlike morphine, hydromorphone does not have an active 6-glucuronide metabolite. This metabolite of morphine can accumulate in the presence of renal failure; therefore, the lack of an active 6-glucuronide metabolite makes hydromorphone a useful alternative to morphine in elderly patients with renal failure. However, hydromorphone is similar to morphine in that it is metabolized to hydromorphone-3-glucuronide, which may be neuroexcitatory. Because of its low plasma protein binding and low probability of interfering with the metabolism of other drugs, hydromorphone may be especially suitable for patients taking multiple medications. OROS hydromorphone is an effective analgesic that is well tolerated and provides more stable plasma concentrations than immediate-release forms of hydromorphone. Its once-daily administration offers an advantage over immediate-release forms and longer-acting formulations that require twice-daily administration. This means OROS hydromorphone will be more convenient for elderly patients and may improve adherence, resulting in improved pain relief and quality of life.