Adverse event profile of tramadol in recent clinical studies of chronic osteoarthritis pain

Abstract

Objective:

To review the safety profile of tramadol hydrochloride (tramadol) in the treatment of chronic osteoarthritis pain, with specific reference to the incidence of adverse events (AEs) reported in large clinical trials.

Methods:

An extensive review of published clinical trials with tramadol was conducted, using literature searches in MEDLINE and EMBASE (since 1997) and the key search terms: tramadol, immediate-release (IR), extended-release (ER), sustained-release (SR), chronic pain, and osteoarthritis. Studies were included based on appropriate study design, appropriately reported safety data, and chronic osteoarthritis as a pain condition. Secondary analyses of previously published pain studies were excluded.

Results:

Fifteen studies met the inclusion criteria. The most common AEs reported across all tramadol formulations were nausea, dizziness, constipation, vomiting, somnolence, and headache. Most AEs were mild to moderate in severity and occurred more commonly during initial treatment than during maintenance treatment. Differences in the rates of selected gastrointestinal and central nervous system AEs were seen between long-acting and immediate-release tramadol formulations, both within individual studies and across all studies. AEs appeared to be dose-dependent in fixed-dose studies.

Conclusions:

This review provides a robust base for descriptive assessment of AEs associated with long-acting tramadol formulations. Although the actions of different tramadol formulations are biologically similar, differences in pharmacokinetics, drug-release patterns, and availability may influence the incidence of AEs associated with tramadol. Because of the limitations of a qualitative safety analysis across studies with different populations and study designs, any observed differences should be interpreted with caution, but these differences may help educate healthcare providers about tramadol treatment in patients with chronic osteoarthritis pain and help them select the optimal dose for specific patients.

Key words::

• Chronic pain
• Extended-release
• Immediate-release
• Nonmalignant
• Osteoarthritis
• Randomized
• Sustained-release
• Tramadol

Transparency

Declaration of funding

This work was supported by Ortho–McNeil Janssen Scientific Affairs, LLC.

Declaration of financial/other relationships

P.C.L. has disclosed that he is a consultant to Johnson & Johnson. C.J.-B. and J.R.S. have disclosed that they are employees and stockholders of J&J. A.D.P. has disclosed that at the time of the study, she worked at Xcenda and was a consultant to J&J. Currently she is an employee and stockholder of J&J. K.A.B. has nothing to disclose.

Some peer reviewers receive honoraria from CMRO for their review work. The peer reviewers of this paper have disclosed that they have no relevant financial relationships.

Acknowledgment

Jonathan Latham provided medical editing assistance on behalf of Ortho–McNeil Janssen Scientific Affairs. The authors thank Byron DeLemos for his critical review of the manuscript.

Notes

* Contramid is a registered trade name of Labopharm, Inc., Laval, Québec, Canada.

† SmartCoat is a trademark of Biovail Laboratories International SRL and is used under license by Biovail Corporation, Mississauga, Ont., Canada.