title: Clinical pharmacology of methadone for pain.
abstract: BACKGROUND
  This topical review addresses methadone's pharmacology, its application in malignant and non-malignant pain conditions, practical issues related to methadone for the treatment of pain and its influence on QTc time.
  
  
  METHODS
  Relevant papers were identified in PubMed and EMBASE.
  
  
  RESULTS
  Methadone is advocated by experts as a second line opioid when first line opioids fail to provide a satisfactory balance between pain control and side effects (opioid switching). Although randomized-controlled studies are lacking, current evidence suggests that switching to methadone in this situation reduces pain intensity. However, interindividual variability in its pharmacokinetics make its application challenging and metabolism by CYP 3A4 and 2B6 implies a substantial risk of drug-drug interactions. Several ways of switching to methadone have been presented, with a gradual switch during 3 days or 'stop and go' as the dominating strategies. Episodes of torsade de pointes arrhythmia during methadone treatment have been reported in patients with other risk factors for arrhythmia, while small prospective studies have reported a small, lasting and stable increase in QTc time. The extensive use of methadone for opioid replacement in addicts has added additional patient barriers to its use for pain control.
  
  
  CONCLUSIONS
  In spite of challenges related to the variable pharmacokinetics and concerns regarding increase in QTc time, current evidence indicates that opioid switching to methadone improves pain control in a substantial proportion of patients who are candidates for opioid switching. Measures must be instituted to secure that patients receiving methadone for pain are not considered opioid addicts.
authors.affiliation: Pain and Palliation Research Group, Department of Circulation and Medical Imaging, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway. olavmagn@ntnu.no
authors.forename: O M S
authors.initials: OM
authors.lastname: Fredheim
authors.forename: K
authors.initials: K
authors.lastname: Moksnes
authors.forename: P C
authors.initials: PC
authors.lastname: Borchgrevink
authors.forename: S
authors.initials: S
authors.lastname: Kaasa
authors.forename: O
authors.initials: O
authors.lastname: Dale
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002908:Chronic Disease; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data; D004347:Drug Interactions; D006801:Humans; D008691:Methadone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D010146:Pain / Q000188:drug therapy*; D010166:Palliative Care / Q000379:methods
chemical_list: D000701:Analgesics, Opioid; D008691:Methadone