What medications can cause clinically significant QTc (QT interval corrected) prolongation?

From the Guidelines

Medications that can cause clinically significant QTc prolongation include antiarrhythmics, antibiotics, antipsychotics, antidepressants, antiemetics, and methadone, with the risk increasing with higher doses and combination therapy, as noted in the 2006 ACC/AHA/ESC guidelines 1. These medications can expose subclinical congenital long QT syndrome and interact with other factors such as female gender, hypokalemia, bradycardia, and congestive heart failure to increase the risk of torsades de pointes. Some of the specific medications that can cause QTc prolongation include:

• Antiarrhythmics: disopyramide, dofetilide, ibutilide, procainamide, quinidine, sotalol, and amiodarone 1
• Antibiotics: clarithromycin, erythromycin, halofantrine, pentamidine, and sparfloxacin 1
• Antipsychotics: chlorpromazine, haloperidol, mesoridazine, thioridazine, and pimozide 1
• Antiemetics: domperidone and droperidol 1
• Opioid dependence agents: methadone 1 It is essential to consider these risk factors and monitor patients closely when prescribing these medications, as intravenous magnesium and temporary pacing may be necessary to manage torsades de pointes 1. Key factors to consider when managing patients on these medications include:
• Checking baseline QTc and monitoring electrolytes
• Starting with lower doses when possible
• Considering ECG monitoring during treatment
• Avoiding combination therapy with multiple QT-prolonging medications whenever possible
• Being aware of the potential for drug interactions and genetic predisposition to increase the risk of QTc prolongation 1.

From the FDA Drug Label

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) Fluoroquinolones, macrolide antibiotics, and azoles are known to cause QTc prolongation. Elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using levofloxacin with concomitant drugs that can result in prolongation of the QT interval (e.g., Class IA or Class III antiarrhythmics) or in patients with risk factors for torsade de pointes (e.g., known QT prolongation, uncorrected hypokalemia)

The medications that can cause clinically significant QTc prolongation include:

• Class 1A antiarrhythmics (e.g., quinidine, procainamide) 2
• Class III antiarrhythmics (e.g., amiodarone, sotalol) 2
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine) 2
• Antibiotics (e.g., gatifloxacin, moxifloxacin) 2
• Fluoroquinolones (e.g., levofloxacin) 3
• Macrolide antibiotics 4
• Azoles 4
• Pentamidine 2
• Levomethadyl acetate 2
• Methadone 2

From the Research

Medications that Cause Clinically Significant QTc Prolongation

Medications that can cause clinically significant QTc prolongation include:

• Antiarrhythmic drugs such as amiodarone, sotalol, quinidine, procainamide, verapamil, and diltiazem 5
• Antipsychotic medications, particularly:
  • First-generation antipsychotics like chlorpromazine, intravenous haloperidol, sultopride, and levomepromazine 6
  • Certain atypical antipsychotics such as thioridazine and ziprasidone 7, 6
• Antibiotics including macrolides and fluoroquinolones 5, 8
• Antidepressants:
  • Tricyclic antidepressants 8
  • Selective serotonin reuptake inhibitors (SSRIs), with citalopram being more likely to induce QTc prolongation than others 7
• Antiemetics like ondansetron and prochlorperazine 5, 8
• Other medications such as domperidone, venlafaxine, and quetiapine, which may contribute to QTc prolongation, especially when used in combination with other medications or in patients with underlying risk factors 9

Risk Factors and Considerations

It's essential to consider the risk factors for QTc prolongation and torsades de pointes (TdP) when prescribing these medications, including:

• Polypharmacy, which can increase the risk of QTc prolongation 9
• Underlying electrolyte disturbances such as hypokalemia and hypomagnesemia 9, 8
• Female gender, bradycardia, and other clinical conditions that may predispose patients to QTc prolongation 8
• Close monitoring and regular ECG checks are crucial, especially in critically ill patients or those with multiple risk factors 5