To review the pharmacodynamics, pharmacokinetics, efficacy, tolerability, dosing, and role of oral oxymorphone immediate-release (IR) and extended-release (ER).
A MEDLINE/PUBMED search (1970 to September 2006) of English language studies. Additional references were obtained from their bibliographies.
All human studies of oxymorphone were reviewed.
Oral oxymorphone IR/ER tablet formulations were approved in June 2006. Oxymorphone, a semi-synthetic -opioid receptor agonist structurally similar to hydromorphone, has an oral bioavailability of approximately 10%. Oxymorphone is extensively metabolized to oxymorphone-3-glucuronide and the active 6-hydroxyoxymorphone. Rapid clearance mandates every four- to six-hour dosing (IR) and every 12-hour dosing (ER). Hepatic impairment, renal impairment, and aging enhance systemic exposure. Oxymorphone IR was superior to placebo and oxycodone IR (acute pain studies). Oxymorphone ER was superior to placebo and equivalent to oxycodone CR and morphine CR (one acute and five chronic pain studies). Oxymorphone exhibits the expected opioid side effects, being comparable to oxycodone and morphine in clinical trials. Coadministration with ethanol causes "dose-dumping" (ER) and increases intersubject variability in drug absorption. Oxymorphone IR is indicated for the relief of moderate-to-severe pain, while oxymorphone ER is indicated for persistent pain. Initial doses (opioid-naïve) are 10 mg to 20 mg every 4 to 6 hours (IR) and 5 mg every 12 hours (ER). Dosage adjustment is recommended in mild hepatic impairment (Child-Pugh class A), renal impairment (creatinine clearance below 50 mL/min), and in the elderly.
Oxymorphone is the newest oral opioid to enter a crowded marketplace now totaling 12 Schedule 2 opioids. It does not appear to have any unique assets or liabilities and should be considered as one of many oral opioids for the management of acute and persistent pain of moderate-to-severe intensity.
"Oral oxymorphone IR/ER tablet formulations are a semisynthetic opioid receptor agonist structurally similar to hydromorphone. Elderly patients can have increased plasma levels and systemic effects (Guay 2007 "
[Show abstract][Hide abstract] ABSTRACT: The evaluation of pain and the subsequent issue of pain control is a clinical challenge that all healthcare providers face. Pain in the elderly population is especially difficult given the myriad of physiological, pharmacological, and psychological aspects of caring for the geriatric patient. Opiates are the mainstay of pain treatment throughout all age groups but special attention must be paid to the efficacy and side effects of these powerful drugs when prescribing to a population with impaired metabolism, excretion and physical reserve. In a random chart review of 300 US veterans, 44% of those receiving an analgesic also received opioids. The increasing use of opiates for pain management by healthcare practitioners requires that those prescribing opioids be aware of the special considerations for treating the elderly. This article will address the precautions one must take when using opiates in the geriatric population, as well as the side effects and ways to minimize them.
Clinical Interventions in Aging 02/2008; 3(2):273-8. · 2.08 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study assessed the potential effects of age, sex, and prior opioid use on the response to oxymorphone extended release (ER) in patients with moderate to severe chronic low back pain.
Combined data from 2 placebo-controlled clinical trials with an enriched-enrollment, randomized-withdrawal design were analyzed. In patients aged > or =18 years with chronic low back pain, the dose of oxymorphone ER was titrated to a stable, tolerable, effective dose. Patients who completed titration were randomly assigned to a 12-week double-blind study period with oxymorphone ER or placebo. Oxymorphone immediate release 5 mg was permitted q4-6h, as needed for rescue medication or withdrawal symptoms, for 4 days after randomization and restricted to 10 mg/d thereafter. Pain intensity (100-mm visual analog scale [VAS]; 0 = no pain to 100 = worst pain imaginable) and time to study discontinuation due to lack of efficacy were compared with stratification by age (<65 vs > or =65 years), sex, and prior opioid use. Adverse events were categorized by severity and relation to study medication.
Of 575 patients, 348 completed titration and 347 entered the double-blind study phase. There were no significant between-group differences in demographic variables, except that the mean age in the oxymorphone ER group was significantly higher (P = 0.04), and the proportion of men was significantly lower (P = 0.01). There was no significant age difference between the oxymorphone ER and placebo groups stratified by age (<65 vs > or =65 years). Fewer patients aged > or =65 years versus <65 years completed titration (45.0% [36/80] vs 63.0% [312/495]; P = 0.002). The least-squares mean (SEM) differences in VAS pain scores between the oxymorphone ER (n = 174) and placebo (n = 169) groups were significant at each postbaseline assessment (P < 0.001) and at study completion (12.3 [2.8] mm; P < 0.001) and was not significantly affected by age, sex, or prior opioid use. Age and sex had no significant influence on adverse events or discontinuations due to lack of efficacy. More discontinuations due to lack of efficacy occurred among patients in the placebo group (hazard ratio, 5.01; P < 0.001) and among opioid-experienced patients. The latter effect was limited to opioid-experienced patients who received placebo. The rates of discontinuation due to lack of efficacy were similar between oxymorphone ER-treated opioid-naive and opioid-experienced patients (11.4% vs 11.6%). The proportion of patients who experienced opioid-related adverse events was significantly greater in the oxymorphone ER group compared with the placebo group (25.7% vs 16.3%; P = 0.03). The most frequent treatment-emergent adverse events in the oxymorphone ER group were nausea (8.0%), constipation (6.3%), vomiting (4.6%), and diarrhea (4.0%); in the placebo group were nausea (5.8%), diarrhea (4.7%), and increased sweating (2.3%).
In the enriched population of patients who successfully titrated to oxymorphone ER, oxymorphone ER was effective and generally well tolerated, independent of patients' age, sex, or previous opioid use.
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