Tapentadol Extended Release Investigated for Low Back Pain

Allison Gandey

October 13, 2009

October 13, 2009 (Baltimore, Maryland) — New pain inventory results suggest that tapentadol extended release may ease chronic low back pain. Presenting here at the 134th annual meeting of the American Neurological Association, investigators suggest the new formulation relieves pain with fewer gastrointestinal effects than oxycodone. However, at 75.5%, the incidence of treatment-emergent adverse effects with tapentadol is still high.

An immediate-release oral tablet (Nucynta, Johnson & Johnson) has already been approved by the US Food and Drug Administration (FDA) for moderate to severe acute pain. The drug acts as both an opioid and nonopioid agent. The new molecular entity is structurally similar to tramadol (Ultram, Grünenthal). Tapentadol is as a μ-opioid-receptor agonist but also inhibits reuptake of norepinephrine, which may have an analgesic effect.

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Dr. Mila Etropolski describes the challenge of adverse events with analgesics.

Researchers hope the dual-action approach will improve efficacy and circumvent many of the adverse events associated with opioids such as constipation, nausea, and vomiting, which often lead to the discontinuation of therapy.

As reported by Medscape Neurology in May, results from a recent phase 3 placebo-controlled trial showed that the new extended-release formulation of tapentadol appears to be safe and effective in low back pain. The work was funded by Johnson & Johnson in New Jersey and Grünenthal in Germany. These latest results are based on the pain inventory questionnaire from the original 15-week trial.

Investigators studied 981 patients with low back pain. Participants were randomly assigned to receive placebo, tapentadol 100 to 250 mg, or oxycodone HCI controlled release 20 to 50 mg.

During a poster session walking tour at the meeting, Mila Etropolski, MD, senior director and clinical leader for Johnson & Johnson, gave a short talk. "Tapentadol extended release reduced the interference of pain on physical function," she said.

Pain Inventory Results

Analgesic Reduction in Pain Interference Subscale Score (P Value) Pain Subscale Score (P Value) Total Score (P Value)
Tapentadol <.001 <.001 <.001
Oxycodone =.023 <.001 =.002

Dr. Etropolski emphasized the safety profile of the new formulation, including fewer gastrointestinal events than oxycodone. According to a recent FDA news release, the most common adverse events with tapentadol are nausea, vomiting, dizziness, sleepiness, and headaches.

The incidence of treatment-emergent adverse events during the trial was 59.6% for placebo, 75.5% for tapentadol, and 84.8% for oxycodone.

During the question period at the meeting, attendees wanted to know about the risk for addiction with tapentadol. Current labeling for the immediate-release formulation includes warnings about the risk for respiratory depression; addictive depressive effects on the central nervous system when taken with alcohol, other opioids, or illicit drugs; and the potential for abuse.

Second-Line Therapy

Asked by Medscape Neurology to comment on the trial when it was first presented this spring, Roger Chou, MD, from the Oregon Health and Science University in Portland, said: "Since there were no differences in pain relief, the potential advantage of tapentadol really lies in its superior safety profile."

However, Dr. Chou questioned the discontinuation numbers in the study. "It's interesting that tapentadol had a lower risk for discontinuation due to adverse events, but overall discontinuation rates were similar. This suggests that people stopped tapentadol for other reasons — possibly because it was less beneficial," he said.

Dr. Chou explained that he would like to see more information on how the researchers evaluated safety and also more on why people discontinued the different drugs. He said that because the 2 treatments showed similar effects in terms of pain relief, it makes sense from a clinical standpoint to use oxycodone first and to only consider tapentadol, which will likely be more expensive, for patients who develop intolerable adverse effects.

This study was supported by Johnson & Johnson Pharmaceutical Research and Development and Grünenthal GmbH. Senior investigator Dr. Mila Etropolski is a senior director and clinical leader at Johnson & Johnson.

American Neurological Association 134th Annual Meeting: Poster M5. Presented October 12, 2009.


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