Methadone induced torsade de pointes in a patient receiving antiretroviral therapy.

St James's Hospital, Dublin.
Irish medical journal (Impact Factor: 0.51). 100(10):631-2.
Source: PubMed

ABSTRACT Adverse drug reactions account for approximately 5% of acute medical admissions. A 34-year-old male patient receiving antiretroviral therapy, methadone and flurazepam presented to the emergency room following collapse with associated loss of consciousness. Cardiac monitoring demonstrated marked Q-T prolongation followed by the cardiac arrhythmia, torsade de pointes. The patient made a full recovery following withdrawal of the antiretroviral therapy and a reduction in methadone dose. Methadone is a recognised cause of this potentially fatal cardiac arrhythmia which is more likely to occur when methadone metabolism is inhibited by drugs such as HIV tease inhibitors.

5 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: We describe 2 cases of symptomatic ventricular tachycardia associated with prolonged QT interval. Both patients were infected with the human immunodeficiency virus and were receiving treatment with ritonavir-boosted atazanavir and methadone. Discontinuation of atazanavir in both cases resulted in a reduction in the QT interval and cessation of arrhythmia. We concluded that atazanavir contributed to prolonged corrected QT interval and subsequent ventricular tachycardia. © 2008 by the Infectious Diseases Society of America. All rights reserved.
    Clinical Infectious Diseases 09/2008; 47(3):e36-8. DOI:10.1086/589869 · 8.89 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: DESCRIPTION: An independent panel developed cardiac safety recommendations for physicians prescribing methadone. METHODS: Expert panel members reviewed and discussed the following sources regarding methadone: pertinent English-language literature identified from MEDLINE and EMBASE searches (1966 to June 2008), national substance abuse guidelines from the United States and other countries, information from regulatory authorities, and physician awareness of adverse cardiac effects. RECOMMENDATION 1 (DISCLOSURE): Clinicians should inform patients of arrhythmia risk when they prescribe methadone. RECOMMENDATION 2 (CLINICAL HISTORY): Clinicians should ask patients about any history of structural heart disease, arrhythmia, and syncope. RECOMMENDATION 3 (SCREENING): Obtain a pretreatment electrocardiogram for all patients to measure the QTc interval and a follow-up electrocardiogram within 30 days and annually. Additional electrocardiography is recommended if the methadone dosage exceeds 100 mg/d or if patients have unexplained syncope or seizures. RECOMMENDATION 4 (RISK STRATIFICATION): If the QTc interval is greater than 450 ms but less than 500 ms, discuss the potential risks and benefits with patients and monitor them more frequently. If the QTc interval exceeds 500 ms, consider discontinuing or reducing the methadone dose; eliminating contributing factors, such as drugs that promote hypokalemia; or using an alternative therapy. RECOMMENDATION 5 (DRUG INTERACTIONS): Clinicians should be aware of interactions between methadone and other drugs that possess QT interval-prolonging properties or slow the elimination of methadone.
    Annals of internal medicine 02/2009; 150(6):387-95. · 17.81 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Numerous established and potential drug interactions with methadone are clinically important in people treated with methadone either for addiction or for chronic pain. Methadone users often have comorbidities and are prescribed drugs that may interact with methadone. Methadone is extensively metabolized by cytochrome P450 (CYP) 3A4 and to a lesser extent by CYP 1A2, 2D6, 2D8, 2C9/2C8, 2C19, and 2B6. Eighty-six percent of methadone is protein bound, predominately to α1-acid glycoprotein (AGP). Polymorphisms in or interactions with CYPs that metabolize methadone, changes in protein binding, and other pathophysiological conditions affect the pharmacokinetic properties of methadone. It is critical for health care providers who treat patients on methadone to have adequate information on the interactions of methadone with other drugs of abuse and other medications. We set out to describe drug-drug interactions as well as physiological and pathophysiological factors that may impact the pharmacokinetics of methadone. Using MEDLINE, we conducted a systematic search for papers and related abstracts published between 1966 and June 2010. Keywords that included methadone, drug-drug interactions, CYP P450 and AGP identified a total of 7709 papers. Other databases, including the Cochrane Database of Systematic Reviews and Scopus, were also searched; an additional 929 papers were found. Final selection of 286 publications was based on the relevance of each paper to the topic. Over 50 such interactions were found. Interactions of methadone with other drugs can lead to increased or decreased methadone drug levels in patients and result in potential overdose or withdrawal, respectively. The former can contribute to methadone's fatality. Prescribers of methadone and pharmacists should enquire about any new medications (including natural products and over-the-counter medications) periodically, and especially when an otherwise stable patient suddenly experiences drug craving, withdrawal or intoxication.
    Critical Reviews in Clinical Laboratory Sciences 07/2011; 48(4):171-95. DOI:10.3109/10408363.2011.620601 · 3.69 Impact Factor
Show more