drug-induced prolonged QT interval

Drugs associated with QT prolongation include (1):

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:

CSM/MCA (1996), drug-induced prolongation of the QT interval, Current Problems in Pharmacovigilance, 33, 1-2.
RCGP (2007). Drug misuse and dependence: UK guidelines on clinical management
NHS Specialist Pharmacy Service (January 2020). What issues should be considered regarding drug-induced QT prolongation?

Last edited 10/2020 and last reviewed 12/2020

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