[1. World Health Organization. WHO model list of essential medicines, http://www.who.int/medicines/publications/essentialmedicines/en/index.html (2005).]Search in Google Scholar
[2. U.S. Food and Drug Administration. Methadone Hydrolcholoride. FDA alert [11/2006]: death, narcotic overdose, and serious cardiac arrhythmias. [updated 2008 August 23; cited 2006 Nov 29] Available from: http://www.fda.gov/cder/drug/advisory/methadone.htm]Search in Google Scholar
[3. Cruciani RA. Methadone: to ECG or not to ECG...That is still the question. J Pain Symptom Manage. 2008 Nov;36(5):545-52.10.1016/j.jpainsymman.2007.11.003]Search in Google Scholar
[4. Kristensen, K, Christensen, C, The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. Life Sci. 56, L45–L50 (1995).10.1016/0024-3205(94)00426-S]Search in Google Scholar
[5. Gorman, A.L., Elliott.The d- and l-isomers of methadone bind to the non-competitive site on the N-methyl-Daspartate (NMDA) receptor in rat forebrain and spinal cord. Neurosci. Lett. 223, 5–8 (1997).10.1016/S0304-3940(97)13391-2]Search in Google Scholar
[6. Corkery JM, Schifano F, Ghodse AH, Oyefeso A. The effects of methadone and its role in fatalities. Hum Psychopharmacol. 2004;19:565–76.10.1002/hup.63015378662]Search in Google Scholar
[7. Eap, C.B., Buclin, T. & Baumann, P. Interindividual variability of the clinical pharmacokinetics of methadone: implications for the treatment of opioid dependence. Clin. Pharmacokinet.41, 1153–1193 (2002).10.2165/00003088-200241140-0000312405865]Search in Google Scholar
[8. Gerber, J.G., Rhodes, R.J. & Gal, J. Stereoselective metabolism of methadone N-demethylation by cytochrome P4502B6 and 2C19. Chirality 16, 36–44 (2004).10.1002/chir.1030314628297]Search in Google Scholar
[9. Crettol, S. et al. Methadone enantiomer plasma levels CYP2B6, CYP2C19 and CYP2C9 genotypes, and response to treatment. Clin. Pharmacol. Ther. 78, 593–604 (2005).]Search in Google Scholar
[10. McCance-Katz EF, Sullivan LE, Nallani S. Drug interactions of clinical importance among the opioids, methadone and buprenorphine, and other frequently prescribed medications: a review. Am J Addict 2010; 19:4–16.10.1111/j.1521-0391.2009.00005.x333428720132117]Search in Google Scholar
[11. Faggiano F, Vigna-Taglianti F, Versino E, Lemma P. Methadone maintenance at different dosages for opioid dependence. Cochrane Database Syst Rev 2003; 3: CD00220810.1002/14651858.CD00220812917925]Search in Google Scholar
[12. Lasser KE, Allen PD, Woolhandler SJ, Himmelstein DU, Wolfe SM, Bor DH. Timing of new black box warnings and withdrawals for prescription medications. JAMA 2002;287:2215-20.10.1001/jama.287.17.221511980521]Search in Google Scholar
[13. Bazett HC. An analysis of the time-relations of electrocardiograms. Heart 1920; 7:353–70.]Search in Google Scholar
[14. Committee for Proprietary Medicinal Products (CPMP). Points to consider: the assessment of the potential for QT interval prolongation by non-cardiovascular medicinal products. The European Agency for the Evaluation of Medicinal Products. December 1997 [CPMP/986/96].]Search in Google Scholar
[15. Priori SG, Schwartz PJ, Napolitano C, et al. Risk stratification in the long-QT syndrome. N Engl J Med 2003;348:1866-74.10.1056/NEJMoa02214712736279]Search in Google Scholar
[16. Sanguinetti, M.C, Jiang, C, Curran, M.E. & Keating, M.T. A mechanistic link between an inherited and an acquired cardiac arrhythmia: HERG encodes the IKr potassium channel. Cell 81, 299–307 (1995).10.1016/0092-8674(95)90340-2]Search in Google Scholar
[17. Katchman, A.N. et al. Influence of opioid agonists on cardiac humanether-a-go-go-related gene K+ currents. J. Pharmacol. Exp. Ther. 303,688–694 (2002). xxx. Kornick, C.A. et al. QTc interval prolongation associated with intravenous methadone. Pain 105, 499–506 (2003).10.1016/S0304-3959(03)00205-7]Search in Google Scholar
[18. Kornick, C.A. et al. QTc interval prolongation associated with intravenous methadone. Pain 105, 499–506 (2003).10.1016/S0304-3959(03)00205-7]Search in Google Scholar
[19. Wieneke H, Conrads H, Wolstein J, Breuckmann F, Gastpar M, Erbel R, Scherbaum N. Levo-alphaacetylmethadol (LAAM) induced QTc-prolongation - results from a controlled clinical trial. Eur J Med Res. 2009 Jan 28;14(1):7-12.10.1186/2047-783X-14-1-7335220519258204]Search in Google Scholar
[20. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007 Dec 10;167(22):2469-75.10.1001/archinte.167.22.246918071169]Search in Google Scholar
[21. Krantz M. Heterogeneous Impact of Methadone on the QTc Interval: What Are the Practical Implications? J Addict Dis. 2008;27(4):5-9.10.1080/1055088080232431719042586]Search in Google Scholar
[22. Krantz M, Lowery C, Martell B, Gourevitch M and Arnsten J. Effects of Methadone on QT-Interval Dispersion. Pharmacotherapy 2005;25(11):1523–1529.10.1592/phco.2005.25.11.152316232014]Search in Google Scholar
[23. Martell B, MD, Arnsten J, Krantz M, and Gourevitch M. Impact of Methadone Treatment on Cardiac Repolarization and Conduction in Opioid Users. Am J Cardiol 2005;95:915–91810.1016/j.amjcard.2004.11.05515781034]Search in Google Scholar
[24. Maremmani I, Pacini M, Cesaroni C, Lovrecic M, Perugi G, Tagliamonte A. QTc interval prolongation in patients on long-term methadone maintenance therapy. Eur Addict Res. 2005;11(1):44-9.10.1159/00008141615608471]Search in Google Scholar
[25. Mayet S, Gossop M, Lintzeris N, Markides V, Strang J. Methadone maintenance, QTc and torsade de pointes: who needs an electrocardiogram and what is the prevalence of QTc prolongation? Drug Alcohol Rev. 2011 Jul;30(4):388-96.10.1111/j.1465-3362.2010.00237.x21355918]Search in Google Scholar
[26. MHRA and Commission on Human Medicines. Risk of QT interval prolongation with methadone. 2006 May. Report No.: 31.]Search in Google Scholar
[27. Perrin-Terrin A, Pathak A, Lapeyre-Mestre M. QT interval prolongation: prevalence, risk factors and pharmacovigilance data among methadone-treated patients in France. Fundam Clin Pharmacol. 2011 Aug;25(4):503-10.10.1111/j.1472-8206.2010.00871.x]Search in Google Scholar
[28. Anchersen K, Clausen T, Gossop M, Hansteen V, Waal H. Prevalence and clinical relevance of corrected QT interval prolongation during methadone and buprenorphine treatment: a mortality assessment study. Addiction. 2009 Jun;104(6):993-9.10.1111/j.1360-0443.2009.02549.x]Search in Google Scholar
[29. Peles E, Bodner G, Kreek MJ, Rados V, Adelson M. Corrected-QT intervals as related to methadone dose and serum level in methadone maintenance treatment treatment (MMT) patients: a cross-sectional study. Addiction. 2007 Feb;102(2):289-300.10.1111/j.1360-0443.2006.01668.x]Search in Google Scholar
[30. Eap CB, Crettol S, Rougier JS, Schlapfer J, Sintra Grilo L, Deglon JJ, Besson J, Croquette-Krokar M, Carrupt PA, Abriel H. Stereoselective Block of hERG Channel by (S)-Methadone and QT Interval Prolongation in CYP2B6 Slow Metabolizers. Clin Pharmacol Ther. 2007 May; 81(5):719-28.10.1038/sj.clpt.6100120]Search in Google Scholar
[31. Routhier DD, Katz KD, Brooks DE. QTc prolongation and torsades de pointes associated with methadone therapy. J Emerg Med. 2007 Apr;32(3):275-8. Epub 2007 Feb 2.10.1016/j.jemermed.2006.07.027]Search in Google Scholar
[32. Lamont P, Hunt SC. A twist on torsade: a prolonged QT interval on methadone. J Gen Intern Med. 2006 Nov;21(11):C9-C12.10.1111/j.1525-1497.2006.00588.x]Search in Google Scholar
[33. Sanchez Hernandez AM, Atienza Fernandez F, Arenal Maiz A, Gonzalez Torrecilla E, Puchol Calderon A, Almendral Garrote J. Torsades de pointes during methadone treatment. Rev Esp Cardiol. 2005 Oct;58(10):1230-2.10.1016/S1885-5857(06)60403-9]Search in Google Scholar
[34. U.S. Food and Drug Administration. Guidance for Industry: E14 Clinical Evaluation of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic Drugs. Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland; 2005.]Search in Google Scholar
[35. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004 Mar 4;350(10):1013-22.10.1056/NEJMra03242614999113]Search in Google Scholar
[36. Anchersen K, Hansteen V, Gossop M, Clausen T, Waal H. Opioid maintenance patients with QTc prolongation: congenital long QT syndrome mutation may be a contributing risk factor. Drug Alcohol Depend. 2010 Dec 1;112(3):216-9. doi: 10.1016/j.drugalcdep.2010.06.015. Epub 2010 Aug 10.10.1016/j.drugalcdep.2010.06.01520702049]Search in Google Scholar