Issue 21, December 2012 Produced by NHS Greater Glasgow and Clyde Medicines Information Service
DRUG INDUCED QT PROLONGATION
Prolongation of the QT interval can lead to a
What is considered to be a prolonged QT interval?
Recent warnings have highlighted the risk of
The QTc interval is a surrogate marker of proarrhythmic
risk and literature differs with regard to the QTc interval
that would raise concern over development of arrhythmias. As a guide:
Extra vigilance is required by healthcare
professionals to be alert to the risk of drug
Borderline QTc interval >440 ms but <500 ms
Although literature differs, a QTc interval within these
values is considered borderline prolonged. Consideration should be given to dose reduction of QT prolonging drugs
or changing to an alternative non QT prolonging drug.
Prolongation of the QT interval can lead to a life
threatening ventricular arrhythmia known as torsades de
Prolonged QTc Interval >500 ms
pointes which can result in sudden cardiac death. There
A QTc interval >500 ms is clinically significant and likely to
are a number of widely used drugs which are known to
confer an increased risk of arrhythmia. Any drugs which
cause QT prolongation. Recently there have been
prolong the QT interval should be reviewed immediately.
warnings relating to drug-induced QT prolongation for
three commonly used drugs – citalopram, domperidone
and ondansetron.1,2,3 Extra vigilance is required by
Interpretation of the QT interval on an ECG is not
healthcare professionals to be alert to the risk of drug
always straightforward and the value noted on the
induced QT prolongation and drug interactions.
computerised printout may not always be accurate. The following website gives some guidance on
There are three mechanisms by which drugs can interact
interpretation of the QT interval:
and increase the risk of QT prolongation:
Pharmacodynamic Interaction: The concurrent use of
more than one drug that prolongs the QT interval increases
What is considered a significant drug induced
the risk of torsades de pointes and ventricular arrhythmia.
change in QTc interval? Pharmacokinetic Interaction: Some drugs which do
The degree by which a drug changes the QTc interval from
not prolong the QT interval themselves can increase the
baseline is also important. An increase in baseline QTc of
risk of QT prolongation by affecting the metabolism of
less than 5 ms is not considered significant and this is the
drugs that do. Commonly used examples of this include
threshold for regulatory concern. For drugs that increase
drugs such as macrolide antibiotics and antifungals which
the QTc interval by less than 20 ms the data is inconclusive
with regard to arrhythmic risk. A change in baseline QTc
of >20 ms should raise concern and a change of >60 ms
Effects on Electrolytes: Hypokalaemia and
should raise greater concern regarding the potential for
hypomagnesaemia can increase the risk of QT prolongation
arrhythmias.8 Experience in long QT syndrome indicates
e.g. diuretics can interact with QT prolonging drugs by
that for every 10 ms increase in QTc there is a 5% increase
in the risk of arrhythmic events.7 Drug induced QT
prolongation is often dose related. For example,
What is a normal QT interval?
citalopram 20 mg daily has been shown to cause a
mean change in baseline QTc of 7.5 ms; this increases to
The QT interval varies with heart rate. A number of
formulas are used to correct the QT interval for heart rate.
A drug induced increase in QTc interval should be assessed
Once corrected it is expressed as the QTc interval. The
in conjunction with the overall QTc interval.
QTc interval is reported on the ECG printout.
Normal QTc Interval <440 ms What are the risk factors for QT prolongation?
In individual cases of torsades de pointes there are often multiple risk factors present. The main risk factors which should be considered are:8,9,10,11
Electrolyte Disturbances (in particular hypokalaemia, hypomagnesaemia and more
rarely hypocalcaemia). Consider the risk of electrolyte disturbance if the patient has GI
Concomitant use of more than one drug that prolongs the QT interval
Cardiac Disease (of multiple origins, including congestive heart failure, ventricular
Impaired hepatic/renal function (due to effects on drug metabolism)
Thyroid Disease (more common with hypothyroidism and usually normalises with
What medications can cause QT prolongation?
It is not possible to include a full list of all medicines known to increase the QT interval in this
bulletin. A list of medications known to prolong the QT interval can be found at
bsite categorises drugs based on their risk. It is recommended
that you check the lists for drugs commonly used in your area of practice to familiarise yourself
Some of the more commonly encountered drugs that are known to prolong the QT interval are
Antimicrobials Antipsychotics (all have some risk) Antiarrhythmics Antidepressants
Protein kinase inhibitors e.g. sunitinib
Antiemetics Table 1: Drugs that can prolong the QT interval.
This list is not exhaustive but is designed to give examples of more commonly used drug
What can be done to minimise the risks of drug induced QT prolongation?
The risk of torsades de pointes depends on patient factors and medication history. A safe drug
in one patient may be potentially harmful in another. The risks and benefits must be
Consider the risk of QT prolongation when starting a new medicine (if unsure of
medicine related risk contact pharmacy for advice)
Assess patient’s risk factors for QT prolongation
Avoid QT prolonging drugs in patients with congenital long QT syndrome
Correct any modifiable risk factors such as electrolyte disturbance
Where a patient has risk factors and / or is prescribed an interacting medicine, the first line option is to change to an alternative drug that is not known to prolong the QT interval whenever possible. When would ECG monitoring be recommended?
It is not practical to recommend an ECG every time a QT prolonging medicine is prescribed,
particularly in primary care. The decision should be made on a case by case basis taking into
account any additional risk factors the patient has. The following could be considered as a
Consider carrying out a baseline ECG prior to starting a QT prolonging drug in
patients with risk factors then repeat when the medicine reaches steady state
Specialist areas that routinely use QT prolonging drugs may consider developing their
own protocols for baseline and follow up ECG monitoring
If there is no alternative to using two drugs in combination that are known to prolong
the QT interval, especially in patients with additional risk factors, carry out an ECG at
baseline and then repeat when the new medicine is likely to reach steady state
If long term use of two medicines that can prolong the QT interval is deemed
necessary the patient should be followed up and monitored via specialist clinic
Any patient on a QT prolonging drug who reports symptoms such as palpitations,
lightheadedness and dizziness should be referred for investigation.
If the decision is made to concurrently prescribe two drugs that are known to prolong the QT
interval this should be clearly documented in the medical notes. If the combination is contra-
indicated specialist advice must be sought.
See flowchart and patient scenarios for further information and guidance.
1. Medicines and Healthcare products Regulatory Agency. Citalopram and escitalopram: QT interval
prolongation – new maximum daily dose restrictions (including in elderly patients),
contraindications and warnings. Drug Safety Update Dec 2011, Vol 5, issue 5:A1
2. Medicines and Healthcare products Regulatory Agency. Domperidone: smal risk of serious
ventricular arrhythmia and sudden cardiac death. Drug Safety Update May 2012, vol 5, issue
3. Medicines and Healthcare products Regulatory Agency. Ondansetron (Zofran): risk of QTc
prolongation – important new intravenous dose restriction. Drug Safety Update Aug 2012, vol 6
4. Yap YG, Camm AJ. Drug Induced QT Prolongation and Torsades de Pointes. Heart
5. Al-Khatib SM, Allen LaPointe NM, Kramer JM, Califf RM. What clinicians should know about the
6. Zareba W. Drug induced QT prolongation. Cardiology Journal 2007;14(6):523-533
7. Taylor D, Paton C, Kapur S. The South London and Maudsley NHS Foundation Trust Oxleas NHS
Foundation Trust. Prescribing Guidelines in Psychiatry. 11th Edition 2012. Wiley Blackwell
Baxter K (ed), Stockley’s Drug Interactions. [online] London: Pharmaceutical Press
www.medicinescomplete.com (accessed April 2012).
9. Roden DM. Drug Therapy: Drug induced prolongation of the QT interval. NEJM
10. Heist EK, Ruskin JN. Drug-induced arrhythmia. Circulation 2010;122:1426-1435
11. Drew BJ, Ackerman MJ, Funk M, Gibler B, Kligfield P, Menon V et al. Prevention of Torsades de
Pointes in hospital settings. A scientific statement from the American Heart Association and the
American College of Cardiology Foundation. Circulation 2010;121:1047-1060
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