A postmarketing surveillance program to monitor Ultram (R) (tramadol hydrochloride) abuse in the United States

Tramadol HCl, marketed as Ultram(R) in the USA, was introduced as a non-sch eduled drug in April 1995 based on the assumption that the risk of abuse wa s sufficiently low to warrant a non-scheduled status. However, approval was contingent upon the development of an innovative proactive surveillance pr ogram, to be overseen by an independent steering committee, which would det ect unexpectedly high levels of abuse. The postmarketing surveillance progr am consisted of systematic collection and scientific evaluation of reports of suspected abuse in high-risk populations surveyed through an extensive k ey informant network of drug abuse specialists and all spontaneous reports of abuse received through the FDA MedWatch system. Methods to estimate the number of patients prescribed tramadol were also developed. Monthly rates o f abuse were calculated as an index of the risk-benefit ratio (i.e., abuse cases per 100 000 patients prescribed the drug). The data for the 3 years s ince the drug was introduced show that the reported rate of abuse has been low. Although a period of experimentation seemed to occur in the first 18 m onths after its introduction-which reached a peak rate of approximately two cases per 100 000 patients exposed-during the 2 year period prior to June 1998, the reported rate of abuse has significantly (P = 0.011) declined, re aching levels of less than one case per 100 000 patients in the last 18 mon ths. The overwhelming majority of abuse cases (97%) have been found to occu r among individuals with a history of substance abuse and the abuse has bee n confined to isolated pockets around the country-notably none of which hav e significant populations of street drug abusers. Thus, the data support th e decision not to schedule tramadol and, furthermore, suggest that a proact ive post-marketing surveillance program can be successfully developed to ef fectively monitor abuse of new medications. (C) 1999 Elsevier Science Irela nd Ltd. All rights reserved.