What can increase the corrected QT (QTc) interval?

From the Guidelines

QTc prolongation can be caused by various medications, electrolyte abnormalities, and medical conditions, and it is crucial to monitor and manage these factors to prevent potentially fatal ventricular arrhythmias, as recommended by the 2016 ESC position paper 1. The medications that can increase QTc include antiarrhythmics, certain antibiotics, antipsychotics, antidepressants, and antiemetics, as well as cancer therapies such as arsenic trioxide and tyrosine kinase inhibitors (TKIs) 1. Some of the key medications that can prolong QTc are:

• Antiarrhythmics (amiodarone, sotalol, procainamide)
• Certain antibiotics (macrolides like azithromycin, fluoroquinolones like ciprofloxacin)
• Antipsychotics (haloperidol, quetiapine)
• Antidepressants (citalopram, escitalopram)
• Antiemetics (ondansetron) Electrolyte disturbances that can prolong QTc include:
• Hypokalemia
• Hypomagnesemia
• Hypocalcemia Medical conditions that can increase QTc include:
• Congenital long QT syndrome
• Heart failure
• Bradycardia
• Hypothyroidism The mechanism typically involves delayed repolarization of cardiac cells due to blockade of potassium channels, which extends the action potential duration and manifests as QT prolongation on ECG, as explained in the American Heart Association scientific statement 1. It is essential to check baseline ECG, monitor electrolytes, avoid combining multiple QT-prolonging drugs, and be especially cautious in patients with existing cardiac disease or risk factors, as recommended by the European Society of Cardiology 1. In patients receiving treatment with arsenic trioxide, weekly ECG monitoring is recommended, and treatment should be temporarily interrupted if QTc is ≥500 ms or QTc prolongation is ≥60 ms above baseline, with electrolyte abnormalities corrected and cardiac risk factors controlled before resuming treatment at a reduced dose 1.

From the FDA Drug Label

Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin. Fatalities have been reported Avoid clarithromycin in the following patients: patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, including torsades de pointes patients receiving drugs known to prolong the QT interval patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents.

The following can increase QTc:

• Clarithromycin itself
• Drugs known to prolong the QT interval
• Uncorrected hypokalemia or hypomagnesemia
• Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents 2

From the Research

Factors that can Increase QTc

• Hypokalemia (low potassium levels) 3, 4, 5
• Female sex 6, 3, 4
• Advanced age (>65 years) 6, 3, 4
• Uncorrected electrolyte disturbances 6
• Bradycardia (slow heart rate) 3, 4
• Heart failure with reduced ejection fraction 3
• Hypomagnesemia (low magnesium levels) 3, 4
• Hypocalcemia (low calcium levels) 3
• Treatment with diuretics 3, 5
• Use of QTc-prolonging drugs, such as:
  • Antifungal agents 3
  • Macrolide antibiotics (except azithromycin) 3
  • Antidepressants (e.g. bupropion, duloxetine, fluoxetine, paroxetine) 3, 7
  • Antipsychotics (e.g. thioridazine, ziprasidone) 7
• Drug interactions, such as:
  • Concurrent use of multiple QTc-prolonging drugs 3
  • Use of drugs that inhibit the metabolism of QTc-prolonging drugs 3
• Genetic predisposition 4
• History of a prolonged QTc interval or Torsades de Pointes 4
• Familial history of cardiovascular disease 5

Medications that can Increase QTc

• QTc-prolonging medications, such as:
  • Antiarrhythmic drugs 3, 5
  • Antidepressants (e.g. citalopram) 7
  • Antipsychotics (e.g. thioridazine, ziprasidone) 7
• Medications that can cause electrolyte disturbances, such as:
  • Diuretics 3, 5