Fatal arrhythmias — drugs and the QT

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Practice points | Why is the QT interval important? | Understanding the QT interval | Do you need to perform an ECG? | Recent medicine safety updates | Information for patients |


The potential for some medicines to cause serious cardiac arrhythmias, which could lead to sudden death, has been the subject of recent medicine safety updates from the TGA and the US FDA.

Health professionals need to be aware of which medicines have known QT effects and to consider the risks before prescribing them.

Practice points

  • Know QT-prolonging medicines
    Be aware of which medicines may prolong the QT interval.
  • Check family history
    Before prescribing medicine(s) with known potential for QT effects, take a complete patient history and determine whether there is a family history of long-QT syndrome.
  • Know risk groups
    Groups with a higher risk of fatal arrhythmia due to QT prolongation include:1,2
    • people with a known history or family history of QT-interval prolongation such as those with torsades de pointes, congenital long-QT syndrome, bradyarrhythmias or uncompensated heart failure
    • people taking other medicines known to increase the QT interval or affect the metabolism of QT-interval-affecting medicines (Table 1)
    • people with proarrhythmic conditions such as uncorrected hypokalaemia or hypomagnesaemia
    • older people and those with cardiac disease, who may be more susceptible to QT-interval prolongation effects.
  • Check OTC medicines
    Be aware that some OTC medicines, such as the antihistamine loratadine, may also have QT-prolongation effects.
  • Advise patients
    Advise the patient of potential adverse effects of the medicine and ensure they know what to do if they experience any signs or symptoms.
  • When to assess
    In high-risk patients assess QT interval before and after starting a medicine with a potential for QT interval effects.
  • When to avoid medicines with QT effect
    In high-risk patients avoiding medicines with known potential for QT effects may be prudent.

Why is the QT interval important?

The QT interval is the time between depolarisation and repolarisation of the ventricles in readiness for the next contraction, and when this is prolonged the interval between myocardial contractions increases. QT-interval prolongation is associated with potentially fatal cardiac arrhythmias.3

Drugs and the QT interval

The evidence that some medicines produce QT-interval effects has been accumulating since the 1960s.3,4

Documented cases of sudden death due to arrhythmias resulted in several medicines being removed from the market or their use severely restricted.3,4 As a result, regulatory bodies such as the TGA require the QT effect of any new medicine to be fully assessed before approval.5,6

QT-prolonging medicines — a growing list

Due to the regulatory requirements surrounding QT interval effect investigation, there is now a comprehensive and continually updated list of drugs that have been shown to have the potential to affect the QT interval.1,2,5,6

Table 1 summarises drugs most commonly associated with QT-interval prolongation.6 This list is by no means exhaustive; however, other resources are available to help with medicine choice:

  • the TGA provides regular updates on safety advice regarding QT-interval prolongation1
  • other sources of information may be helpful when deciding on medicine choice.

Table 1. Some of the medicines identified as having potential QT-interval effects (recent updates and warnings in bold)1,6

Anti-arrhythmic drugs



Some SSRIs: citalopram, escitalopram, fluoxetine
Most tricyclic antidepressants






fluoroquinolones: ciprofloxacin, moxifloxacin, sparfloxacin
Macrolides: azithromycin,2 clarithromycin, erythromycin, roxithromycin
Antifungals: fluconazole, voriconazole
Antimalarials: chloroquine mefloquine
Other antimicrobials: pentamidine

Other drugs


Understanding the QT interval

The QT interval is measured from the start of the QRS complex to the end of the T wave in an  ECG.7 It is the time between myocardial contractions, when the ventricular myocardium is repolarising in readiness for the following contraction4,7 (Figure 1).

Prolongation of the QT interval is a delay in cardiac repolarisation and is considered a biomarker for serious tachyarrhythmias, in particular, torsade de pointes, which can degenerate into ventricular fibrillation and sudden death.4,5

Pathology of EGC traces

Figure 1. ECG trace showing normal sinus rhythm, QT prolongation and torsade de pointes.

Factors that contribute to cardiac arrhythmia

In addition to certain drugs, a variety of other factors can contribute to QT-interval prolongation such as:3,4,6,8

  • familial long-QT syndrome
  • cardiac pathology
  • electrolyte abnormality
  • thyroid dysfunction.

It is important to remember that factors other than the medicine itself may increase the risk of fatal arrhythmia.

Some medicine combinations may lead to pharmacokinetic interactions and changes in drug metabolism that may exacerbate a QT-interval effect.6 For example, ketoconazole is known to exacerbate the effects of cisapride by inhibiting its metabolism by the cytochrome P450 enzyme 3A4.6

Prescribing practices may put patients at risk

A US study of prescribing practice in about 5 million patients found that around 20% of patients filled prescriptions for medicines with known QT-interval effects.9 Of these patients, 9.4% filled prescriptions for medicine combinations that placed them at an increased risk of QT prolongation.This was either through the prescription of more than one medicine with a known QT effect or through the prescription of medicines that affect drug clearance.9

Do you need to perform an ECG?

Evidence is lacking on how to effectively assess risk–benefit in individual patients.6

The reliability of ECG in identifying QT interval effects and predicting which individuals will go on to develop serious cardiac arrhythmias is low.6,8

The most accurate way to measure QT interval is with high-resolution 12-lead ECG from continuous Holter monitor recordings.6 A computer algorithm is used to estimate the QT length.6

Assessment in general practice

It may not be practical to perform a 12-lead ECG in every patient for whom a medicine is being considered with potential QT-interval effects.

Consider assessing QT interval only in patients suspected of being at high risk of developing torsade de pointes before and after starting a medicine with known QT effects (see Practice points).8

Avoiding medicines with known QT effects altogether may be prudent in particularly high-risk patients, such as those with existing cardiac disease, bradyarrhythmias, long-QT syndrome and older people.8

Managing arrhythmia

Stop suspect medicines if a patient experiences brief self-terminating episodes of ventricular tachycardia.7 No other treatment for tachycardia is specifically required except for treatment of any metabolic abnormalities that may have precipitated the event.7

Recent medicine safety updates

The most recent TGA and FDA medicine safety updates have highlighted QT-interval effects in three medicines — ondansetron,1 domperidone1 and azithromycin.2 The FDA and TGA recommend caution when prescribing these medicines, particularly in patients at increased risk of developing QT-interval prolongation.


The 32 mg intravenous dose of ondansetron is no longer recommended, while the recommendations for oral and rectal formulations remain the same.1


There is evidence that increased risk of QT-interval prolongation occurs with daily doses of domperidone > 30 mg, or in patients older than 60 years.1 Therefore domperidone should be started at the lowest effective dose and adjusted upward with caution.


The FDA recommend the QT-interval prolongation risk with azithromycin be weighed against its need as an alternative antimicrobial agent, as other medicines in the macrolide or fluoroquinolone classes also affect the QT interval.2

Information for patients

If prescribing medicines with known QT effects ensure the patient is fully aware of the risks and warning signs of dangerous heart rhythms such as palpitations or syncope.

  • Advise patients to notify their GP if they develop conditions that may put them at increased risk of QT-interval prolongation, such as severe gastroenteritis.1
  • Reassure patients that dangerous heart rhythm is a rare event even when they are taking medicines that prolong the QT interval.
  1. Australian Government Department of Health and Ageing, Therapeutic Goods Administration. Medicines Safety Update. December 2012;3. http://www.tga.gov.au/hp/msu-2012-06.htm (accessed 18 March 2013).
  2. U.S. Food and Drug Administration. FDA Drug Safety Communication: Azithromycin (Zithromax or Zmax) and the risk of potentially fatal heart rhythms. Drug Safety Communications 2013. http://www.fda.gov/drugs/drugsafety/ucm341822.Htm (accessed 18 March 2013).
  3. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med 2004;350:1013–22. [PubMed]
  4. Zareba W. Drug induced QT prolongation. Cardiol J 2007;14:523–33. [PubMed]
  5. Australian Government Department of Health and Ageing, Therapeutic Goods Administration. EU Guidelines – as adopted in Australia by the TGA – with amendment. Note for guidance on the clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs. CHMP/ICH/2/04. 2006. http://www.tga.gov.au/pdf/euguide/ich000204entga.pdf (accessed 18 February 2013).
  6. Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol 2012;Nov 20.doi:10.1111/bcp.12040 [Epub ahead of print]. [PubMed]
  7. Jayasinghe R, Kovoor P. Drugs and the QTc interval. Aust Prescr 2002;25:63–5.
  8. Al-Khatib SM, LaPointe NM, Kramer JM, et al. What clinicians should know about the QT interval. JAMA 2003;289:2120–7. [PubMed]
  9. Curtis LH, Ostbye T, Sendersky V, et al. Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients. Am J Med 2003;114:135–41. [PubMed]