Itraconazole‐induced Torsade de Pointes in a patient receiving methadone substitution therapy

Robson, Noorzurani; Vicknasingam, Balasingam; Narayanan, Suresh

doi:10.1111/j.1465-3362.2009.00128.x

Cited by 15 publications

(7 citation statements)

References 20 publications

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“…Itraconazole, an antifungal pharmacological agent, has been reported to cause long QT and TdP in patients receiving terfenadine and also in patients undergoing methadone substitution therapy . Unfortunately, we were unable to test this interaction in our data.…”

Section: Discussionmentioning

confidence: 99%

Validation of a population‐based method to assess drug‐induced alterations in the QT interval: a self‐controlled crossover study

Iribarren

Round

Peng

et al. 2013

Pharmacoepidemiology and Drug

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Section: Discussionmentioning

confidence: 99%

Validation of a population‐based method to assess drug‐induced alterations in the QT interval: a self‐controlled crossover study

Iribarren

Round

Peng

et al. 2013

Pharmacoepidemiology and Drug

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“…Noorzurani et al 117 reported that a 44-year-old woman who was admitted following an episode of chest discomfort and syncope had been receiving 120 mg of methadone daily for the past nine months, and had consumed 200 mg of itraconazole, prescribed the day before. Her ECG (electrocardiogram) showed a QT c interval of 520 ms leading to torsade de pointes, which resolved spontaneously.…”

Section: Itraconazolementioning

confidence: 98%

Methadone: a review of drug-drug and pathophysiological interactions

Kapur

Hutson²,

Chibber

et al. 2011

Critical Reviews in Clinical Laboratory Sciences

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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.

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“…Rhabdomyolysis has been reported in patients on the combination of itraconazole and statins [ 36 ]. Prolonged QTc interval leading to Torsade de points has also been reported when co-administered with methadone [ 37 ] and terfenadine, but not the newer antihistamines [ 38 ]. Treatment will often require adjustments to the non-azole treatment and switching to a non-CYP3A4 metabolised alternative.…”

Section: Treatmentmentioning

confidence: 99%

The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis Centre Approach

Maghrabi

Denning

2017

Curr Fungal Infect Rep

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Purpose of ReviewChronic pulmonary aspergillosis (CPA) is a serious long-term fungal disease of the lung with a worldwide prevalence. Treatment of CPA is not straightforward given the often-multiple associated co-morbidities, complex clinical picture, drug interactions, toxicities and intolerances.Recent FindingsFirst line treatment is oral itraconazole or voriconazole. In the event of intolerance or toxicity, patients may be swapped from itraconazole to voriconazole or vice versa. In the event of resistance or further intolerance, third line treatment with posaconazole could be initiated. In those with pan-azole resistance, short-term courses of intravenous liposomal amphotericin B or micafungin are fourth line therapy, keeping in mind the nephrotoxic effects of amphotericin B.SummaryThe available evidence for current treatments in CPA is limited and based mostly on retrospective cohort studies. There is a real need to raise awareness of this devastating disease to enable early treatment as well as prospective drug trials and studies to identify potential patient factors that correlate with progression, severity and overall outcomes in order to target future therapies.

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Itraconazole‐induced Torsade de Pointes in a patient receiving methadone substitution therapy

Abstract: Implication: This cardiac arrhythmia was most likely due to drug interaction between methadone and itraconazole because the patient presented with no other risk factors.

Cited by 15 publications

References 20 publications

Validation of a population‐based method to assess drug‐induced alterations in the QT interval: a self‐controlled crossover study

Validation of a population‐based method to assess drug‐induced alterations in the QT interval: a self‐controlled crossover study

Methadone: a review of drug-drug and pathophysiological interactions

The Management of Chronic Pulmonary Aspergillosis: The UK National Aspergillosis Centre Approach

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