What medications increase the QT(c) (corrected QT) interval?

From the Guidelines

Medications that can increase the QTc interval include antiarrhythmic drugs, antibiotics, antipsychotics, antidepressants, antiemetics, antimalarials, methadone, and some antihistamines, with the most significant risk associated with drugs like thioridazine, ziprasidone, and quetiapine, as reported in a study published in 2016 1. These medications can affect cardiac repolarization by blocking potassium channels in heart cells, delaying the return to resting state after contraction. The risk of QTc interval prolongation is also increased with the use of certain medications such as chloroquine and hydroxychloroquine, as noted in a 2020 study 1. Other medications that can increase the QTc interval include:

• Antiarrhythmic drugs like amiodarone, sotalol, procainamide, and quinidine
• Antibiotics including macrolides, fluoroquinolones, and pentamidine
• Antipsychotics such as haloperidol, thioridazine, ziprasidone, and quetiapine
• Antidepressants like citalopram, escitalopram, and tricyclic antidepressants
• Antiemetics like ondansetron and domperidone
• Antimalarials like chloroquine and hydroxychloroquine
• Methadone and some antihistamines like terfenadine and astemizole Patients with existing heart conditions, electrolyte abnormalities, or those taking multiple QTc-prolonging medications are at higher risk for developing dangerous arrhythmias like Torsades de Pointes, as highlighted in a 2006 guideline 1 and a 2017 guideline 1. Regular ECG monitoring is recommended when these medications are prescribed, particularly in high-risk patients, as suggested in a 2014 proposal for clinical management 1. It is essential to assess cardiac risk before initiation of treatment, evaluate the QT interval before and during treatment, and avoid concomitant treatment with more than one drug that can prolong the QT interval.

From the FDA Drug Label

In clinical trials, quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10. 1)] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS (7.1)] . 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.

The following medications may increase the QTc interval:

• Quetiapine 2: may increase QTc interval, especially in patients with concomitant illness or taking medicines known to cause electrolyte imbalance or increase QT interval.
• Clarithromycin 3: has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Medications to avoid with quetiapine or clarithromycin due to increased risk of QT prolongation:
• Class 1A antiarrhythmics (e.g., quinidine, procainamide)
• Class III antiarrhythmics (e.g., amiodarone, sotalol)
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine)
• Antibiotics (e.g., gatifloxacin, moxifloxacin)
• Other medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

From the Research

Medications that Increase QTc Interval

The following medications have been associated with an increased QTc interval:

• Antipsychotics:
  • Thioridazine 4, 5, 6, 7
  • Haloperidol 4, 5, 6, 7
  • Ziprasidone 4, 5, 6, 7
  • Quetiapine 5, 6, 7
  • Olanzapine 5, 6, 7
  • Risperidone 5, 6, 7
  • Sertindole 6
  • Pimozide 5, 6
  • Clozapine 5 (although some studies suggest no association 7, 8)
• Antidepressants:
  • Citalopram 4
  • Amitriptyline 6
  • Imipramine 6
  • Doxepin 6
  • Trazadone 6
  • Fluoxetine 6
• Other medications:
  • Droperidol 6
  • Valproate 7 (although used as an alternative in patients with prolonged QTc interval)
  • Benzodiazepines 7 (although used as an alternative in patients with prolonged QTc interval)

Factors that Influence QTc Interval

In addition to medications, the following factors can influence the QTc interval:

• Age 6, 8
• Sex (female gender) 5, 6
• Congestive heart failure 5
• Hypokalemia 5
• Hypomagnesemia 5
• Bradycardia 5
• Polymorphisms of genes coding ion channels or enzymes involved in drug metabolism 5
• Polygenic variation 8
• Potassium serum concentrations 8