title: Usefulness of methadone plasma concentration measurement in patients receiving nevirapine or efavirenz.
abstract: OBJECTIVE
  To determine methadone plasma trough and peak concentrations in patients presenting opiate withdrawal symptoms after introduction of nevirapine or efavirenz. To describe the disappearance of these symptoms after methadone titration based on plasma concentrations rather than on the symptoms.
  
  
  METHODS
  Nine patients undergoing highly active antiretroviral therapy (HAART) and either nevirapine or efavirenz treatment were monitored daily for opiate withdrawal in a specialized drug addiction center. Methadone dose was titrated daily, and plasma concentrations were measured. The data are retrospective (case series).
  
  
  RESULTS
  Several patients complained of symptoms such as nausea, vomiting, accelerated intestinal transit, or insomnia. Even after methadone titration based on clinical symptoms, patients and health-care providers trained in infectious disease did not classify these as withdrawal symptoms and considered them as the side effects of HAART or anxiety. Methadone plasma trough concentration showed low levels of (R)- and (R,S)-methadone. Further methadone dose adjustment according to plasma level resulted in the disappearance of these withdrawal symptoms. The daily methadone dose was split when the peak/trough (R)-methadone ratio was more than 2.
  
  
  CONCLUSIONS
  When introducing efavirenz or nevirapine to patients undergoing methadone treatment, withdrawal symptoms should be monitored, especially those such as insomnia, vomiting, or nausea. Methadone plasma trough and peak measurements can be of value in preventing unnecessary side effects of HAART.
authors.affiliation: Department of Ambulatory Care and Community Medicine, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Pelet
authors.forename: Bernard
authors.initials: B
authors.lastname: Favrat
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Chin B
authors.initials: CB
authors.lastname: Eap
authors.forename: Jacques
authors.initials: J
authors.lastname: Besson
authors.forename: Martine
authors.initials: M
authors.lastname: Monnat
mesh_terms: D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects*; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008691:Methadone / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000188:drug therapy*
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz; D008691:Methadone