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.

• methadone
• pharmacokinetic
• plasma trough level and withdrawal symptoms

ACKNOWLEDGMENTS

We thank all patients for their participation in this study

Funding: This study was not supported by any funding.

Contribution of each author: Anne Pelet gathered the clinical information, performed statistical analysis, and wrote the manuscript. Bernard Favrat supervised the methodology and revised the manuscript. Matthias Cavassini revised the manuscript and supervised the HIV consultation including all HIV-related issues. Chin B. Eap provided useful insight concerning methadone titration, dosage, and trough and peak level interpretation, reviewed the manuscript, and consulted in the international literature review on methadone pharmacokinetics. Jacques Besson reviewed the manuscript and provided useful insights related to drug addiction issues. Martine Monnat supervised the writing of the manuscript and the clinical work related to drug addiction.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.