Trends in Reporting Methadone-Associated Cardiac Arrhythmia, 1997–2011 (original) (raw)
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Arrhythmia associated with buprenorphine and methadone reported to the food and drug administration
Addiction, 2015
Aim-To assess the relative frequency of reporting of adverse events involving ventricular arrhythmia, cardiac arrest, QTc prolongation, or torsade de pointes to the US Food and Drug Administration (FDA) between buprenorphine and methadone. Design-Retrospective pharmacoepidemiologic study Setting-Adverse drug events spontaneously reported to the FDA between 1969-June 2011 originating in 196 countries (71% events from the US). Cases-Adverse event cases mentioning methadone (n=14,915) or buprenorphine (n=7,283) were evaluated against all other adverse event cases (n= 4,796,141). Measurements-The primary outcome was the composite of ventricular arrhythmia or cardiac arrest. The secondary outcome was the composite of QTc prolongation or torsade de pointes. The proportional reporting ratio (PRR) was used to identify disproportionate reporting defined as a PRR>2, χ2 error>4, with ≥3 cases. Findings-There were 132 (1.8%) ventricular arrhythmia/cardiac arrest and 19 (0.3%) QTc prolongation/torsade de pointes cases associated with buprenorphine compared with 1729 (11.6%) ventricular arrhythmia/cardiac arrest and 390 (2.6%) QTc prolongation/torsade de pointes cases involving methadone. PRRs associated with buprenorphine were not significant for ventricular arrhythmia/cardiac arrest (1.1 95% confidence interval (CI) 0.9-1.3, χ2=1.2) or QTc prolongation/ torsade de pointes (1.0 95% CI 0.7-1.9, χ2=0.0006), but were for methadone (7.2 95% CI 6.9-7.5, χ2=9160; 10.6 95% CI 9.7-11.8, χ2=3305, respectively). Conclusion-In spontaneously reported adverse events, methadone is associated with disproportionate reporting of cardiac arrhythmias, whereas buprenorphine is not. Although these findings probably reflect clinically relevant differences, a causal connection cannot be presumed
Metabolites, 2021
Methadone-related deaths are characterized by a wide range of post-mortem blood concentrations, due to the high pharmacokinetic/dynamic inter-individual variability, the potential subjective tolerance state and to other risk factors or comorbidities, which might enhance methadone acute toxicity. In the present study, the association among pre-existing and external conditions and diseases and the resultant methadone death capacity have been investigated. Beside a systematic literature review, a retrospective case-control study was done, dividing cases in which methadone was the only cause of death (controls), and those with associated clinical-circumstantial (naive/non-tolerant state), pathological (pulmonary or cardiovascular diseases) or toxicological (other drugs detected) conditions. Methadone concentrations were compared between the two groups and the association with conditions/diseases was assessed by multiple linear and binomial logistic regressions. Literature cases were 139...
Methadone Toxicity Fatalities: A Review of Medical Examiner Cases in a Large Metropolitan Area*
Journal of Forensic Sciences, 2007
Over the past several years, Medical Examiners in Kentucky and around the nation have observed a dramatic rise in drug intoxication deaths involving the prescription medication methadone. This documented rise in methadone-related deaths requires a better understanding of methadone's pathophysiology and the ways it contributes to significantly increase morbidity and mortality. This study reviews 176 fatalities ascribed to methadone toxicity by the Office of the Chief Medical Examiner in Kentucky between 2000 and 2004. Postmortem toxicological analysis recorded a more than 10-fold increase in methadone toxicity fatalities, rising from 6 cases in 2000 to 68 cases in 2003. Of the 176 methadone-related fatalities, methadone was the only drug detected in postmortem blood and urine toxicological analyses in 11 (6.25%) cases. The mean methadone blood concentration of all 176 cases was 0.535 mg ⁄ L (0.02-4.0). The following psychoactive medications were detected: antidepressants (39.8%), benzodiazepines (32.4%), and other opioids in addition to methadone (27.8%). Cannabinoids were detected in 44 (28.4%) cases and cocaine or metabolite in 34 (21.9%) cases. Of the 95 cases with a known history of methadone use, 46 (48.4%) involved prescription by private physician. The interpretation of blood methadone concentrations alone or combined with other psychoactive drugs requires consideration of the subject's potential chronic use of and tolerance to the drug. A thorough investigation into the practices of procurement and use ⁄ abuse of methadone is essential to arrive at the proper designation of the cause of death.
Addiction, 2009
Aims To describe all people dying from unintentional overdoses of methadone or other opioid analgesics (OOA) in West Virginia in 2006. Design We analyzed medical examiner data supplemented by data from the state prescription drug monitoring program. We compared people whose deaths involved methadone with those whose deaths involved OOA. Findings The methadone group included 87 decedents, and the OOA group included 163 decedents. Most were male. Decedents in the methadone group were significantly younger than those in the OOA group: more than a quarter were 18-24 years of age. For both groups, approximately 50% had a history of pain, and 80% had a history of substance abuse. There was no intergroup difference in the prevalence of benzodiazepines at post-mortem. Methadone was significantly less likely to have ever been prescribed than OOA. Among those with prescriptions, the proportion prescribed within 30 days of death was significantly greater for methadone than for hydrocodone, but not for oxycodone. Ten (11.5%) of the methadone decedents were enrolled in an opiate treatment program (OTP) at the time of death. Conclusions The high prevalence of a substance abuse history and lack of prescriptions suggest that most of the deaths in both groups are related to substance abuse. There was no indication of a harmful effect from methadone's metabolic interaction with benzodiazepines, but provider or patient unfamiliarity with methadone may have been a risk factor. Prescribing methadone, especially to young males, requires extra care. Providers, OTPs and coroners/ medical examiners should use state prescription drug monitoring programs to monitor the use of controlled substances by their patients.
The effects of methadone and its role in fatalities
Human Psychopharmacology-clinical and Experimental, 2004
Methadone is a synthetic opioid, used both as an analgesic in severe pain relief and now mainly in the treatment of opiate dependence. Such use of the drug has increased as its advantages have become widely recognized. There are undesirable outcomes from its greater use, including a substantial market in diverted methadone and a high number of deaths where the drug has been implicated. It is important to understand how and why methadone causes death so that such fatalities can be minimized, and to disseminate such information. This paper presents an overview of the chief effects of methadone on the human body, considering its metabolism, drug interactions and tolerance. The principal mechanisms by which methadone causes death are discussed: respiratory depression, aspiration of vomit, pulmonary oedema, bronchopneumonia, cardiac problems and renal failure. Many such deaths are preventable, if drug interactions and polydrug use are avoided, its longer period of metabolism and individuals' tolerance levels are considered. It is hoped that this paper will (a) help guide health professionals in their management and treatment of patients participating in methadone treatment programmes, and (b) provide some basic information for those dealing with individuals who have consumed methadone.
Methadone-induced Torsade de pointes tachycardias
Swiss Medical Weekly Official Journal of the Swiss Society of Infectious Diseases the Swiss Society of Internal Medicine the Swiss Society of Pneumology, 2005
Methadone is a synthetic opioid frequently used in drug maintenance programs for heroin addicts. It prolongs the QT-interval and is mainly metabolized by the isoenzyme CYP3A4 of the hepatic cytochrome-P450-system, which is used by numerous other QT-prolonging agents. Its most severe side effect is the development of life-threatening Torsade de pointes ventricular tachycardia in the setting of a prolonged QT-interval. Since drug addicts are prone to concomitant medical conditions requiring additional medication as well as to continued abuse of cocaine, they are at higher risk for developing this major complication of methadone therapy. Before subjecting patients on methadone to other drugs, the QT-interval should be determined and it should be ascertained whether the new agent has the property to prolong the QT-interval or is metabolised by the cytochrome-P450 system.
Cardiotoxicity of Oral Methadone as an Analgesic–-Recommendations for Safe Use
Clinical Medicine. Therapeutics
Once used only as third-line therapy in the management of chronic pain states, methadone is now being used as first- and second-line therapy. Most risks and the stigma associated with methadone use have been known for years. Only over the past decade or so have the unique pharmacokinetic-pharmacodynamic properties and methods for conversion from other opioids to methadone been established. Pertinent English-language literature was obtained from MEDLINE/PUBMED and EMBASE searches (1966-June 2009). This paper provides an overview of the cardiotoxicity of oral methadone, with an emphasis on its use as an analgesic. Cardiotoxicity during its use in the maintenance of opioid addiction has also been reviewed due to the wealth of epidemiologic, risk factor, and correlative analytic data contained therein. A series of recommendations are provided to improve the cardiac safety profile of oral methadone used for analgesia. In addition, there is a discussion of settings and patient types which...