title: Methadone toxicity due to smoking cessation--a case report on the drug-drug interaction involving cytochrome P450 isoenzyme 1A2.
abstract: OBJECTIVE
  To report the potential clinically significant pharmacokinetic interaction that may result from smoking cessation in patients on methadone maintenance therapy.
  
  
  METHODS
  A 46-year-old white man was admitted to the step-down intensive care unit with decreased respirations and altered mental status related to methadone toxicity. The patient had been on a stable dose of methadone for chronic back pain, and he reported a 1 pack per day, 33-year history of cigarette smoking. After methadone was held for 3 days, his mental status improved. It was later revealed that he had initiated smoking cessation. He was discharged home on a reduced dose of methadone with no further complications.
  
  
  CONCLUSIONS
  While the potential for toxicity exists for patients who are maintained on methadone and decrease the number of cigarettes they smoke, to our knowledge, there is no recent peer-reviewed literature on this interaction. Methadone is a synthetic opioid primarily metabolized by CYP3A4 and, to a lesser degree, by other isoenzymes, including CYP1A2. Polycyclic aromatic hydrocarbons found in tobacco smoke are known CYP1A2 inducers. Decreased intake of cigarette smoke can lead to a reduction in methadone metabolism, resulting in higher serum concentrations. Our case is an example of methadone toxicity secondary to smoking cessation in a patient on methadone maintenance therapy. An objective causality assessment based on the Horn Drug Interaction Probability Scale revealed the interaction to be probable.
  
  
  CONCLUSIONS
  Patients on methadone should be monitored for signs of methadone toxicity upon the start of smoking cessation, and the dose of methadone should be adjusted accordingly. Additional information and reports cautioning clinicians and patients about this potential interaction would be beneficial.
authors.affiliation: Department of Pharmacy Practice, Irma Lerma Rangel College of Pharmacy, Texas A&M Health Science Center, Kingsville, TX, USA. Wahawisan@pharmacy.tamhsc.edu
authors.forename: Joy
authors.initials: J
authors.lastname: Wahawisan
authors.forename: Srikanth
authors.initials: S
authors.lastname: Kolluru
authors.forename: Tu
authors.initials: T
authors.lastname: Nguyen
authors.forename: Christina
authors.initials: C
authors.lastname: Molina
authors.forename: Joseph
authors.initials: J
authors.lastname: Speake
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D008875:Middle Aged; D012907:Smoking / Q000378:metabolism*; D016540:Smoking Cessation / Q000379:methods*; D014029:Tobacco Use Disorder / Q000534:rehabilitation
chemical_list: D000701:Analgesics, Opioid; D019388:Cytochrome P-450 CYP1A2; D008691:Methadone