Designing a tool allowing for a standardized assessment of resistance to drug diversion.

OBJECTIVES: Drug diversion is a growing problem in numerous countries. Some laboratories have developed tamper-resistant formulations. The problem for healthcare authorities is now to assess new formulations developed to limit the risk of diversion for administration by another mode and intended mode. It would be helpful to have a pertinent panel of in vitro tests allowing assessment of how a formulation may be altered, both for healthcare authorities and for laboratories, so as to implement adequate sanitary measures. We designed a methodology/tool allowing assessment, in a standardized manner, of the formulation's resistance to drug diversion. We present the various steps leading to the construction of the scale and to its first use. METHODS: Creating a Steering Committee - Choosing assays or parameters - standardized by a monograph of the European Pharmacopoeia and pragmatic assays related to users' behaviors - for the assessment of formulation resistance to drug diversion. Designing a scale: i) applying all these tests to a panel of formulations; ii) applying a score by drug and by test; and iii) attribution of weighting per test and calculating the total score for a drug. RESULTS: Eight tests or parameters and 14 drugs (diverted drugs and controls) were chosen. Buprenorphine Subutex® had the lowest score and flunitrazepam Rohypnol® the highest. CONCLUSIONS: Our tool allowed classification of the various drugs selected. This classification correlated with results of postmarketing authorization assessment. Rohypnol®, which was the object of many measures, including formulation changes, obtained the highest score in our study.

Suicidal poisonings with methadone in France: results of a two year national survey by the Toxicovigilance network.

CONTEXT: Methadone is used in France since March 1995, only for opioid maintenance treatment, in a syrup form. For the launching of a capsule form in April 2008, French health authorities requested a prospective survey of all cases involving exposure to methadone in either of the two available pharmaceutical forms. OBJECTIVE: The aim was to document, in different circumstances and compare the safety of the new capsule form to the syrup. This report presents the findings of one arm of the study, devoted to methadone-related suicide attempts. MATERIALS AND METHOD: From April 15, 2008 to April 15, 2010, all self-injurious methadone poisonings notified to or managed by the French Toxicovigilance Centers network were included. Analysis mainly focused on patients' age and gender, estimated quantity ingested, eventual concomitantly taken substances, distribution of symptoms, and site of treatment. RESULTS: 135 methadone-related suicide attempts were recorded. Analysis showed identical epidemiologic and clinical patient characteristics for the two pharmaceutical forms. Ten deaths occurred. The only discrepancy was a higher incidence of suicide attempts in the capsule group. However, as the number of capsule-treated patients increased during the second year, this difference remained significant but tended to decrease. DISCUSSION: Combining these results with Pharmacovigilance and Addictovigilance arms, health authorities estimated that the benefit/risk balance of this new pharmaceutical form remains positive. They revised their position on requirements for prescribing and dispensing of the capsule form, and made them slightly easier. Following this, this "suicide" arm of Toxicovigilance survey was suspended, whereas the second one, concerning accidental pediatric methadone-related poisonings, has been extended until April 2014. CONCLUSION: In France, suicide attempts were more likely to occur with the capsule formulation. The clinical severity of intoxication was similar between the capsule and liquid forms.