New post hoc data from a 1-year safety study of tapentadol extended release show that the drug is well tolerated in low back pain and osteoarthritis.
Investigators presenting here at the American Pain Society 29th Annual Scientific Meeting showed that tapentadol extended release has a strong safety profile and is sometimes better tolerated than oxycodone controlled release.
Still, the most common adverse events with tapentadol are nausea, vomiting, dizziness, sleepiness, and headaches.
Some experts say that even though the Johnson & Johnson product, known as Nucynta, is becoming increasingly well known, it makes sense to use opioids as first-line therapy and to try tapentadol only if the adverse effects become intolerable.
"I'm never quick to jump on the bandwagon for new drugs before the postmarketing surveillance has had an opportunity to identify problems," Gilbert Fanciullo, MD, from Dartmouth-Hitchcock Medical Center in Lebanon, New Hampshire, who was not involved in the study, told Medscape Neurology. "I'm very proprietary of my patients and would never want to put them at risk."
Dr. Fanciullo pointed out that current opioid therapies have more postmarketing experience and are the best first option. "Tapentadol could be initiated second line in patients who are experiencing difficulties," he said. "I am hopeful about the potential for this drug."
Tapentadol acts as both an opioid and nonopioid agent. The new molecular entity is structurally similar to tramadol (Ultram, Grünenthal). "It has 2 mechanisms of action," poster presenter David Biondi, MD, said during an interview. Dr. Biondi works for Ortho-McNeil Janssen, a Johnson & Johnson company. Tapentadol is a μ-opioid-receptor agonist that also inhibits reuptake of norepinephrine, he explained, which could have an analgesic effect.
Tapentadol extended release was initially evaluated in a phase 3, randomized, open-label, 1-year safety study. The work was funded by Johnson & Johnson in New Jersey and Grünenthal in Germany.
The study involved 1117 patients with moderate to severe chronic low back pain or osteoarthritis. Investigators report that tapentadol had similar analgesic effects to oxycodone.
The post hoc analysis of this study focused on the rate of treatment-emergent adverse events. The researchers suggest that tapentadol is associated with better gastrointestinal tolerability than oxycodone.
Treatment-Emergent Adverse Events in at Least 10% of Patients
Extended Release, %
(n = 894)
Controlled Release, %
(n = 223)
|Gastrointestinal|| 52.0|| 64.1|
| - Constipation|| 22.6|| 38.6|
| - Nausea|| 18.1|| 33.2|
| - Vomiting|| 7.0|| 13.5|
| Nervous system|| 45.4|| 39.9|
| - Somnolence|| 14.9|| 11.2|
| - Dizziness|| 14.8|| 19.3|
| - Headache|| 13.3||
In the tapentadol group, 22% of patients experienced an adverse event leading to the discontinuation of treatment; in the oxycodone group, 37% did.
Dr. Biondi and his team did not discuss the overall rate of discontinuation in their poster, but according to previous reports, these numbers were high in both groups (46% for tapentadol and 57% for oxycodone).
Asked by Medscape Neurology to comment on these numbers when they were first presented last spring, Roger Chou, MD, from the Oregon Health and Science University in Portland, said that "since there were no differences in pain relief, the potential advantage of tapentadol really lies in its superior safety profile."
Dr. Gary Vorsanger
However, Dr. Chou wondered about the discontinuation numbers in the study. "It's interesting that tapentadol had a lower risk for discontinuation because of adverse events, but that overall discontinuation rates were similar. This suggests that people stopped tapentadol for other reasons — possibly because it was less beneficial," he said.
Dr. Chou suggests that because the 2 treatments show similar efficacy, it makes sense from a clinical standpoint to use oxycodone first and to only consider tapentadol, which is more expensive, for patients who develop intolerable adverse effects.
The investigators conducted a second post hoc analysis of the study, another poster presentation at the meeting, which evaluated the effect of previous opioid experience on treatment.
About half the patients in the original 1-year safety study had previously taken opioids: 53% of the tapentadol group and 50% of the oxycodone group.
Dr. Biondi reports that patients who had previously taken opioids were less likely to discontinue study treatments.
Effect of Previous Opioid Use on Discontinuations
|No previous opiods ||25.2||53.2|
|Previous opioids ||19.5||20.5|
Coauthor Gary Vorsanger, MD, also from Ortho-McNeil Janssen, pointed out that regardless of a patient's previous opioid use, tapentadol extended release was associated with fewer treatment-related adverse events, gastrointestinal disorders, and discontinuations than oxycodone.
"It is well tolerated and the trends we are seeing are similar to the original safety study," Dr. Vorsanger said during an interview.
The researchers point out that, irrespective of opioid exposure, the most common treatment-related adverse events were typical of μ-opioid-receptor agonists and included gastrointestinal and nervous system disorders.
The studies were supported by Johnson & Johnson and Grünenthal GmbH. Dr. Gilbert Fanciullo reports serving on an early advisory panel for tapentadol. Dr. David Biondi and Dr. Gary Vorsanger report working for Ortho-McNeil Janssen, which is owned by Johnson & Johnson. Dr. Roger Chou has disclosed no relevant financial relationships.
American Pain Society (APS) 29th Annual Scientific Meeting: Posters 265 and 267. Presented May 6, 2010.
Allison Gandey • Medscape Medical News © 2010 Medscape, LLC