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.