long QT (drug induced)

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Drugs associated with QT prolongation include (1):

  • tricyclic antidepressants
  • antiarrhythmics:
    • quinidine
    • disopyramide
    • procainamide
    • amiodarone
    • sotalol
  • non-sedative antihistamine toxicity
    • terfenadine
    • astemizole
  • antimalarials
    • especially halofantrine
  • antipsychotics
    • notably droperidol and thioridazine
  • cisapride

  • methadone

  • cocaine has been shown to increase QT intervals acutely (2)

  • citalopram (3)

  • ondansetron (3)

Normal QT interval (3):

  • QT interval varies with heart rate
  • females have a longer QT interval than males
  • definitions vary in the literature but as a guide, normal QTc intervals are <450 milliseconds (ms) for men and <460 ms for women
  • a QTc between these values and 500 ms is considered prolonged
    • a QTc >500 ms is considered clinically significant and is likely to confer an increased risk of arrhythmia

Magnitude of drug induced changes in QT interval (3):

  • the degree by which a drug changes the QTc interval from baseline is also important
    • an increase in baseline QTc of around 5 ms or less is not considered significant and this is the threshold for regulatory concern
    • for drugs that increase the QTc interval by less than 20 ms the data are inconclusive with regard to arrhythmic risk
      • a change in baseline QTc of >20 ms should raise concern and a change of >60 ms should raise greater concern regarding the potential for arrhythmias
      • evidence from congenital long QT syndrome indicates that for every 10 ms increase in QTc there is a 5-7% increase in risk of torsades de pointes
    • drug-induced QT prolongation is often dose related and risk of torsades de pointes is increased with intravenous administration (particularly if given rapidly).

Notes:

  • it is beyond the scope of GPnotebook to provide a list of all medicines that prolong the QT interval.  The American website http://www.crediblemeds.org/  has regularly updated lists of medicines which cause prolongation of the QT interval.  Information can also be found in the British National Formulary (BNF, available via http://www.evidence.nhs.uk/ ), Summaries of Product Characteristics (SPCs, www.medicines.org.uk) and Stockley’s Drug Interactions (subscription required).  Medicines information departments and pharmacists can help with determining the risks of individual medicines

Reference:

Last edited 10/2020 and last reviewed 10/2020

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