Tramadol extended-release formulations in the management of pain due to osteoarthritis

Abstract

Tramadol is a centrally acting, synthetic analgesic. Its mechanism of action involves weak binding to the μ-opioid receptors and inhibition of reuptake of both norepinephrine and serotonin. It has been used to treat moderate-to-severe pain for 30 years in Europe and more than 10 years in the USA. Initially available in immediate-release form (dosing four- to six-times daily), in recent years, a variety of once-daily formulations have been developed utilizing different extended-release technologies, which provide different pharmacokinetic characteristics (time to reach therapeutic plasma levels, time to steady state and plasma levels at 24 h), leading to different clinical implications (e.g., titration schedule, time to onset and adverse events). This review addresses the efficacy and safety of the four marketed once-daily formulations with published data in studies on osteoarthritis. Analgesic efficacy and safety results from double-blind clinical studies utilizing 100–400 mg daily doses of these once-daily formulations have been published. Most subjects took tramadol 200 or 300 mg/day. Each once-daily formulation demonstrated statistically superior efficacy compared with placebo or similar efficacy to immediate-release or twice-daily tramadol. Availability of short- and long-term safety data varies among the formulations. Generally, adverse events are typical of tramadol (constipation, nausea, dizziness and somnolence). Descriptively, a trend to comparable or lower incidence and severity of adverse events seems apparent with the various once-daily formulations. Tramadol once-daily formulations are more effective than placebo and at least as effective and well tolerated as immediate-release formulations in the treatment of pain due to osteoarthritis, and offer a reduced dosing regimen, which is especially valuable in elderly patients.

Keywords::

• analgesia
• controlled release
• once-daily formulation
• pain
• tramadol

Acknowledgement

The author would like to thank Wendy Smith for her help with the English of this paper.

Financial & competing interests disclosure

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.