What medications are most likely to prolong the QT (quantum time) interval?

From the Guidelines

Medications that are most likely to prolong the QT interval include antiarrhythmics, certain antibiotics, antipsychotics, and antidepressants, with Class IA antiarrhythmics (quinidine, procainamide, disopyramide) and Class III antiarrhythmics (amiodarone, sotalol, dofetilide) carrying the highest risk. The risk of QT interval prolongation is increased with the use of certain medications, including:

• Antiarrhythmics: Class IA (quinidine, procainamide, disopyramide) and Class III (amiodarone, sotalol, dofetilide) 1
• Antibiotics: macrolides (erythromycin, clarithromycin, azithromycin) and fluoroquinolones (moxifloxacin, levofloxacin, ciprofloxacin) 1
• Antipsychotics: haloperidol, thioridazine, and ziprasidone 1
• Antidepressants: citalopram, escitalopram, and tricyclic antidepressants 1
• Other medications: ondansetron, methadone, hydroxychloroquine, and domperidone 1 The risk of QT interval prolongation is also increased in patients with:
• Pre-existing heart conditions
• Electrolyte abnormalities (especially hypokalemia)
• Congenital long QT syndrome
• High drug concentrations, often due to drug interactions
• Rapid rate of intravenous drug administration
• Baseline QT prolongation
• Ventricular arrhythmia
• Left ventricular hypertrophy
• Certain DNA polymorphisms
• Severe hypomagnesemia
• Concomitant use of 2 or more drugs that prolong the QT interval 1 It is essential to note that the risk of QT interval prolongation can be minimized by avoiding the use of multiple QT-prolonging medications, monitoring electrolyte levels, and using the lowest effective dose of the medication 1.

From the FDA Drug Label

5.12 QT Prolongation 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)] . The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

1. 2 QT Prolongation Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointeshave 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 [see also Contraindications (4. 2)] 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.

Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. There have been reports of QTc prolongation, with or without TdP, in patients taking amiodarone when fluoroquinolones, macrolide antibiotics, or azoles were administered concomitantly

The medications most likely to prolong the QT interval are:

• Class 1A antiarrythmics (e.g., quinidine, procainamide)
• Class III antiarrythmics (e.g., amiodarone, sotalol)
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine)
• Antibiotics (e.g., gatifloxacin, moxifloxacin, clarithromycin)
• Other medications (e.g., pentamidine, levomethadyl acetate, methadone) 2, 3, 4

From the Research

Medications that Prolong the QT Interval

The following medications have been associated with QT interval prolongation:

• Macrolides, such as clarithromycin 5, 6, 7, erythromycin 6, and azithromycin 7
• Quinolones 8
• Azoles 8
• Pentamidine 8
• Protease inhibitors 8
• Antimalarial drugs 8
• Cotrimoxazole 8
• Amiodarone 5
• Tramadol 5
• Haloperidol 5
• Fentanyl 5
• Glyceryl trinitrate 5
• Betalactamase inhibitors, such as piperacillin + tazobactam 5
• Quetiapine, particularly when co-prescribed with strong CYP3A4 inhibitors like clarithromycin 7

Risk Factors for QT Interval Prolongation

The following risk factors have been identified:

• Congestive heart failure 5
• Ischemic cardiopathy 5
• Diabetes 5
• Renal failure 5
• Arrhythmias 5
• Hypothyroidism 5
• Bradycardia 5
• Female sex 6
• Older age 6
• Severe illness 6
• Concomitant administration of other QTc prolonging drugs or agents that are substrates for or inhibitors of CYP3A4 6