Extended-release tramadol (ULTRAM®ER):: A pharmacotherapeutic, pharmacokinetic, and pharmacodynamic focus on effectiveness and safety in patients with chronic/persistent pain

Tramadol is a centrally acting synthetic opioid analgesic that has a dual mechanism of action, binding to mu-opioid receptors and weakly inhibiting the neuronal reuptake of norepinephrine and serotonin. Extended-release (ER) tramadol tablets (ULTRAM(R)ER) are indicated for the management of moderate to moderately severe chronic (also referred to as persistent) pain in adults who require around-the-clock treatment of pain for an extended period of time. Because once-daily tramadol ER results in less frequent fluctuations in plasma concentrations than equivalent daily doses of short-acting tramadol, it may benefit patients experiencing pain throughout the dosing interval. On the basis of computer-generated pharmacokinetic models, one can easily transition patients who are receiving short-acting tramadol for chronic/persistent pain to tramadol ER, by calculating the current total daily close of short-acting tramadol and starting tramadol ER at the nearest lower 100-mg-close increment. In clinical studies, tramadol ER significantly reduced pain in patients with chronic pain from osteoarthritis and improved pain-related sleep parameters, joint stiffness, and physical function. Tramadol ER has been shown to be safe and well-tolerated and may be a suitable alternative for patients with inadequate analgesic response or contraindications (eg, cardiovascular disease, gastrointestinal ulcer) to use of nonsteroidal anti-inflammatory drugs (NSAIDs) or cyclooxygenase-2 (COX-2) inhibitors. The proven efficacy and safety profile-and the low potential for abuse-make tramadol ER a viable therapeutic option for the management of chronic/persistent nonmalignant pain in some patients. This article reviews the pharmacology, pharmacokinetics, pharmacodynamics, dosage, delivery system, administration, analgesic efficacy, and safety and tolerability profile of tramadol ER.