In patients with knee osteoarthritis, a once-a-day extended-release (ER) formulation of Tramadol (Ultram) appears to improve symptoms of chronic pain, new research suggests. The findings were presented here Saturday at the American College of Rheumatology (ACR) 66th Annual Scientific Meeting.
The current form of Tramadol, marketed as Ultram, has a short half-life that necessitates dosing every four to six hours. In contrast, once-daily Tramadol ER “offers the advantage of patient convenience and should minimize peak-to-trough fluctuation,” said Kenneth Albert, PhD, senior author and researcher with Biovail Technologies in Chantilly, Virginia.
Filing for U.S. Food and Drug Administration approval of Tramadol ER is “on target” to happen in mid-2003, Dr. Albert told Medscape.
To evaluate the efficacy of Tramadol ER compared with placebo, Dr. Albert and colleagues conducted a randomized trial of 246 patients with radiographically confirmed knee osteoarthritis. All patients were at least 50 years of age and experienced morning stiffness of less than 30 minutes in duration or crepitus, or both.
Patients underwent a two- to seven-day washout period during which they stopped taking any analgesics. When pain at the knee joint reached a level of 40 mm on a visual analogue scale (VAS) scale of 0 to 100 mm, they were randomized to receive Tramadol ER (n=124) or placebo (n=122).
Tramadol ER was first given at a dose of 100 mg once daily, and this was increased to 200 mg once daily after one week. When necessary, subsequent doses of 300 mg or 400 mg per day were given. Overall, the mean study dose was 275 mg per day.
Various measures of arthritis pain and functional ability were assessed, including arthritis pain intensity VAS, WOMAC VAS, stiffness, physical function subscale scores, patient and physician global assessment of therapy, and sleep quality.
Over 12 weeks, average decrease from baseline in arthritis pain intensity VAS was 30.1 mm in patients receiving Tramadol ER compared with 16.1 mm in patients receiving placebo (P>.001), the researchers report.
Other measures of arthritis pain and disability were also improved with Tramadol ER compared with placebo, with significance levels of differences ranging from P>.001 to P>.05. Differences from placebo were evident as early as week one, they point out.
Regarding safety, “over 90% of adverse events were rated mild or moderate in severity,” the researchers report. However, the incidence of adverse events was significantly greater in patients receiving Tramadol ER compared with those receiving placebo, and included nausea, vomiting, fatigue, and dizziness.
Sidney Block, MD, an ACR member and rheumatologist in private practice in Bangor, Maine, told Medscape that the study does indicate that Tramadol ER is effective and relieves pain more than placebo. He also pointed out that the extended-release version is likely to result in a more even dose and a potential reduction in adverse effects such as dizziness and grogginess compared with the current form of Tramadol.
However, Dr. Block noted that the study did not directly compare the effectiveness of Tramadol ER to Tramadol or other medications, “for example, we don’t know how its efficacy compares to that of codeine, nonsteroidal anti-inflammatory drugs, and other pain medications,” he said.
“Tramadol ER will be used,” he said, “but my prediction is that its use will be limited because of cost.” Attempts to change diet and lifestyle and less expensive treatments such as acetaminophen, glucosamine, and propoxyphene napsylate (Darvocet) are indicated before the use of Tramadol, he said.
The study was funded by Biovail Corporation.
Revision date: July 5, 2011
Last revised: by Sebastian Scheller, MD, ScD