Voluntary warnings and the limits of good prescribing behavior: the case for de-adoption of meperidine

BACKGROUND: Meperidine (pethidine) offers little to no therapeutic advantage over other opioids, may be more prone to abuse, and produces a neurotoxic metabolite with a long half-life. The Institute for Safe Medication Practices (ISMP) issued warnings in 2004 and 2005 suggesting that meperidine be avoided, and when used, it should be in limited doses (<600 mg/24 h) and for a limited duration (<48 hours). Hospitals have responded to these warnings, but much less is known about meperidine prescribing in the community setting. This study examined the potential impact of ISMP warnings on the prescribing of meperidine using time series analysis. METHODS: A population-based longitudinal cross-sectional study was conducted to examine oral meperidine utilization among persons 16 years of age and older in Manitoba, Canada, between April 1, 2001 and March 31, 2014. Amounts of meperidine were expressed using defined daily doses (DDDs), the equivalent of 400 mg of meperidine per day. The number of meperidine prescriptions and users per quarter were determined and analyzed using regression analysis. RESULTS: There were 49,063 prescriptions for 442,641 DDDs of meperidine dispensed to 9,374 distinct users. The number of DDDs of meperidine per 1,000 persons peaked in the second quarter of 2003 at 11.75, and then dropped to a low of 5.36 by 2014. This represented a marked decline in the numbers of users and prescriptions over the study period. The piecewise regression model revealed a significant breakpoint in the last quarter of 2004 (F((3, 48))=337.00, P<0.0001). In contrast to these findings, among the remaining users, there was an increase in the amount of meperidine per prescription (increase of 0.34 DDDs/prescription/year; F(1, 50)=434, P<0.0001, R(2)=0.89) and the amount of meperidine per user (increase of 1.17 DDDs/user/year; F(1, 50)=653.5, P<0.0001, R(2)=0.93). CONCLUSION: Following the ISMP warnings, meperidine use dramatically declined. Unfortunately, the remaining users of meperidine are using more meperidine and receiving more meperidine in each prescription. This pattern of results suggests that there may be limits to voluntary safety warnings. Policy action such as removal of medication insurance coverage may represent a logical next step to reverse or de-adopt meperidine and further enhance patient safety.