Morphine is the archetypal opioid analgesic. Because it is a short-acting opioid, its use has been limited to the management of acute pain. The development of extended-release formulations have resulted in the increased utilization of morphine in chronic pain conditions. This review documents the history of morphine use in pain treatment, and describes the metabolism, pharmacodynamics, formulations, and efficacy of the currently available extended-release morphine medications.

Urine drug monitoring is used by physicians treating chronic pain patients with opioid therapy. Patients are tested in part to insure that they are not taking other drugs. Therefore, the finding of codeine in a patient who is only prescribed morphine has clinical implications. Morphine preparations are known to have small amounts of codeine as an impurity estimated to be about 0.04%. In a population of 535 pain patients prescribed morphine, Kadian, MS Contin, and/or Avinza, the investigators observed 24 samples that contained codeine >20 ng/mL. Fifteen of the 24 contained codeine >20 and <50 ng/mL. Of the 9 samples that were >50 ng/mL, 7 had high levels of codeine (indicating codeine use), 1 was from a patient who had a prescription for codeine, and 1 was also positive for 6-acetylmorphine, indicating heroin use. A control group of 680 patients taking oxycodone was negative for codeine. The finding of codeine was ascribed to the manufacturing process of the morphine medications. Clinicians and laboratories testing urine for drugs should be aware of this possibility.

This multicenter trial compared the efficacy, safety, and effect on quality of life and work limitation of once-daily extended-release morphine sulfate capsules (AVINZA, A-MQD) and twice-daily controlled-release oxycodone HCI tablets (OxyContin, O-ER) in subjects with chronic, moderate to severe low back pain. After randomization and a period of opioid dose titration, subjects (n=266) underwent an eight-week evaluation phase and an optionalf our-month extension phase (n=174 in extension phase). Subjects were assessed using the 12-item Short-Form Health Survey (SF-12) and the Work Limitations Questionnaire (WLQ). In both groups, significant improvements were observed in the SF-12 mean scores forp hysicalf unctioning (p < 0.001), role physical (p < 0.0001), bodilyp ain (p < 0.0001), physical summary (p < 0.001), and mental component summary (p < 0.005). At the end of the titration period, greater relative improvements from baseline were seen in the SF-12 section on physical components in the A-MQD group versus the O-ER group, with significant differences observed for physical functioning (p = 0.0374), role physical (p = 0.0341), bodily pain (p = 0.0001), andp hysical summary (p = 0.0022). In both groups, SF-12 mean scores improved significantly for mental health (p < 0.01), role emotional (p < 0.01), socialfunctioning (p < 0.0005), vitality (p < 0.005), and the mental component summary (p < 0.005), but no significant differences were noted between the two groups. Both groups reported improvement from baseline in WLQ physical demands scores, with no significant differences noted between the two groups. At the end of the evaluation phase, fewer subjects were unable to work due to illness or treatment in the A-MQD group than in the O-ER group (8.5 percent versus 19.4 percent, respectively; p = 0.0149). In conclusion, compared to twice-daily OxyContin, once-daily A VINZA resulted in significantly better and earlier improvement ofp hysicalf unction and ability to work.

This large, open-label, randomized, parallel-group, multicenter study compared two oral sustained-release opioids (SROs)--AVINZA (A-MQD), morphine sulfate extended-release capsules given once a day, and OxyContin (O-ER), oxycodone modified-release tablets given twice a day--in SRO-naive subjects ages 30 to 70 with chronic, moderate to severe low back pain. Of the 392 subjects enrolled and randomized, 266 (132 in the A-MQD group and 134 in the O-ER group) completed the opioid dose titration phase and entered an eight-week evaluation phase. During the evaluation phase, A-MQD achieved significantly better pain control than O-ER, as demonstrated by a greater decrease from baseline in pain scores obtained four times daily during weeks one, four, and eight (p = 0.002). The number of breakthrough-pain rescue medication doses adjusted for the number of patient days was significantly lower in the A-MQD group (p < 0.0001). Better pain control with A-MQD was achieved with a significantly lower daily opioid dose than with O-ER (mean 69.9 mg and 91 mg morphine equivalents, respectively; p = 0.0125). Quality of sleep was significantly better with A-MQD for the entire evaluation phase (p = 0.0026). The incidence and severity of elicited opioid side effects were similar in the two groups. This trial demonstrated that once-daily A-MQD provides consistent around-the-clock pain relief in patients with low back pain. In patients who completed opioid dose titration, A-MQD was significantly better than O-ER for reducing pain and improving sleep, while requiring a lower daily opioid dose.

This study evaluated the clinical effects and pattern of use of AVINZA((r)), morphine sulfate extended-release tablets, under real-world treatment conditions. Opioid-naive subjects or subjects who have failed other opioids were eligible if they had chronic moderate-to-severe noncancer pain with an average pain score > or =4 (0-10 scale) in the preceding month. Subjects answered in-depth monthly questionnaires in three months. For the 491 evaluable subjects enrolled, the median AVINZA dose was 30 mg at baseline, titrated to 60 mg by month 1, and remained at 60 mg through month 3. Adherence was high, with almost 90% of the subjects reporting never having forgotten to take AVINZA. Mean daily pain scores (scale 0-10) significantly improved from 7.83 at enrollment to 5.77 at month 1 (P < 0.01) and then remained at this level through month 3. Significant improvements were seen in all sleep measures, and the mean Composite Sleep Score, a global measure of sleep quality (scale 0-10), significantly improved from 5.73 at baseline to 4.96 at month 3 (P < 0.01). Physical functioning was improved for activities requiring a moderate effort (P = 0.053), such as climbing one flight of stairs (P = 0.008). Two hospitalizations for nausea and vomiting were the only reported drug-related serious adverse events. This study showed that once-daily AVINZA significantly reduced pain scores, and resulted in improved sleep and physical functioning in patients with chronic moderate-to-severe pain. These results were achieved with a stable daily morphine dose over the three-month study period.

Avinza is a once-daily, extended-release oral morphine preparation. It has a pharmacokinetic profile that exhibits less peak-to-trough fluctuations in plasma concentration whilst providing analgesia statistically identical to that produced by MS Contin (controlled-release morphine sulfate), Oxycontin (oxycodone HCl controlled-release) and six doses of oral morphine sulfate administered every 4 h. Avinza improves quality of sleep by several measures but interestingly gives the best sleep improvement when given in the morning rather than at night. It causes the same side effects of other opioids: constipation, nausea, vomiting, somnolence and mood swings. Doses of 30 - 60 mg/day have been shown to be well tolerated by patients with osteoarthritis (even in the elderly), who have failed other medications.