Tramadol Extended-Release Tablets in Moderate to Moderately Severe Chronic Pain in Adults1

Abstract

In the management of chronic pain, the oral (least approved in the US; it utilises SmartcoatTM (Biovail invasive) route is preferred for administration of Corporation) technology.[11] This polymer diffuanalgesics.[5] Nonscheduled opioids, such as sion-based film technology[12] is a semi-permeable tramadol, are among the pharmacological agents coating composed of at least one water-insoluble but recommended for the management of chronic pain, water-permeable film-forming polymer, at least one along with NSAIDs and paracetamol.[6] An initial plasticiser and at least one water-soluble polylow dose of analgesic is followed by titration to a mer.[13] The semi-permeable membrane allows dose that alleviates pain without causing dose-limitwater into the tablet core with resulting dissolution ing adverse effects;[5,6] several weeks of pharmaof drug on the core surface.[12,13] Controlled release cotherapy may be required before such therapeutic of drug occurs as an osmotic process that is indepenbenefit appears.[6] dent of the effects of pH or alcohol.[11,14] Tramadol is a synthetic, centrally acting opioid Tramadol ER is administered once daily[15] and is analgesic with well established efficacy in the treattherefore likely to enhance patient convenience and ment of moderate to moderately severe pain.[7] For compliance relative to tramadol IR. The features and the treatment of chronic pain, frequent administraproperties of tramadol ER are presented in table I. tion (at least four times daily) of oral, immediateAt steady state in healthy adult volunteers, release (IR) tramadol is required because of the tramadol ER 200mg administered once daily was rapid (within 2 hours) attainment of peak plasma equivalent in bioavailability to tramadol IR 50mg concentrations (Cmax) and short (≈5–6 hours) elimiadministered four times daily at 6-hour intervals nation half-life of the drug.[8] Consequently, oral formulations of tramadol have been developed that (n = 32)[16] or at a clinically realistic administration provide a more gradual release of the drug, with the schedule of 7:00am, 12:00 noon, 6:00pm and aim of reducing the frequency of administration.[9,10] 10:00pm (n = 15).[17] Absorption of tramadol was prolonged and peak plasma concentrations were The extended-release tablet formulation of lower in subjects who received tramadol ER, relatramadol (tramadol ER) [ULTRAM® ER]2 is the first once-daily, oral formulation of tramadol to be tive to those receiving tramadol IR.[16]