Drug-Induced QTc Interval Prolongation

- February 13, 2020

The risk of developing a life threatening arrhythmia at any given QTc interval (the QT interval corrected for heart rate) varies widely between patients. In patients with a high baseline risk of QTc prolongation, QTc prolonging drugs should be either avoided or the QTc interval should be monitored closely.

QTc Prolongation


Predisposing Risk Factors


Drug Interactions

  • Prolonged QTc interval can lead to Torsades de Points (TdP), ventricular tachycardia, ventricular fibrillation, and sudden death.
  • QTc prolongation is a QTc interval
    > 440 milliseconds (ms) in men or
    > 460 ms in women (definition varies between sources).
  • Risk of arrhythmia increases with increasing QTc interval AND predisposing risk factors.
  • Some drugs prolong cardiac repolarisation. This usually occurs on starting the offending drug(s), and is apparent within days, it is often dose-related and the risk is increased with intravenous administration.
  • Congenital long QT syndrome or past history of long QT.
  • Family history of sudden cardiac death.
  • Structural heart disease (e.g. cardiomyopathy).
  • Hypokalaemia, hypomagnesaemia and hypocalcaemia.
  • Thyroid dysfunction.
  • Bradycardia.
  • Female gender.
  • Age over 65 years.
  • Renal or hepatic impairment can lead to high drug concentrations of drugs that prolong QTc.
  • Two or more drugs that cause QTc prolongation independently will have an additive effect and increase the risk of TdP.
  • One or more drugs may cause electrolyte disturbance (e.g. diuretics, β-agonists, proton pump inhibitors), bradycardia (e.g. β-blockers, donepezil) or other effects that predispose the individual to the QTc prolonging effects of another drug.

Some drugs that can prolong the QTc interval:

Antimalarial drugs Anti-arrhythmic drugs
chloroquine*, mefloquine amiodarone*, disopyramide*, flecainide*, sotalol*
Macrolides Antiemetic drugs
azithromycin*, clarithromycin*, erythromycin*, roxithromycin* domperidone* (doses > 30 mg daily), droperidol*, ondansetron*
Quinolones Antidepressant drugs
ciprofloxacin*, levofloxacin*, moxifloxacin* SSRIs (e.g. citalopram*, escitalopram*), tricyclic antidepressants
Triazole antifungals Antipsychotic drugs
fluconazole*, itraconazole, ketoconazole, voriconazole
Most antipsychotics have a dose related risk of QTc prolongation
artemisia annua, donepezil*, lithium, methadone*, solifenacin, tacrolimus, tamoxifen, tolterodine

*These drugs are classified by CredibleMeds® as a ‘known’ risk of TdP. List is not exhaustive.

Report suspected adverse effects to CARM (including those associated with complementary and alternative medicines (CAMs)).


Prevention of Drug-Induced QTc Prolongation

  • Address modifiable risk factors:
    • Limit the use of QTc prolonging drugs in patients with known risk factors.
    • Use the lowest possible dose and/or administer at a slow rate.
    • Avoid drug interactions, particularly multiple drugs associated with QTc prolongation.
    • Avoid electrolyte disturbances.
  • Review any available ECGs prior to prescribing a QTc prolonging drug, and obtain an ECG prior to starting a second or subsequent potentially QTc-prolonging drug. Dose reduction or discontinuation is recommended if the QTc is > 500 ms or if it increases > 50 ms compared with baseline. Consider cardiology review if prolonged QTc doesn’t resolve with drug discontinuation.
  • Advise patients to seek immediate medical attention if symptoms such as light-headedness, dizziness, palpitations, shortness of breath, or fainting occur.
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