What medications should be avoided in patients with QT interval prolongation?

From the Guidelines

Patients with prolonged QT interval should avoid medications that can further extend the QT interval, including antipsychotics, certain antibiotics, antiarrhythmics, antihistamines, antidepressants, anti-nausea medications, and methadone, as these can increase the risk of dangerous arrhythmias like Torsades de Pointes. These medications block potassium channels in heart cells, delaying cardiac repolarization and prolonging the QT interval 1. The risk of adverse events increases in patients with long QT syndrome with prolongation of the QTc >500 ms, and QT-prolonging medications should not be used in patients with long QT syndrome unless there is no suitable alternative 1. Some medications to avoid include:

• Antipsychotics (haloperidol, thioridazine, ziprasidone)
• Certain antibiotics (macrolides like azithromycin, erythromycin; fluoroquinolones like ciprofloxacin, levofloxacin)
• Antiarrhythmics (amiodarone, sotalol, procainamide)
• Antihistamines (diphenhydramine, hydroxyzine)
• Antidepressants (citalopram, escitalopram)
• Anti-nausea medications (ondansetron, domperidone)
• Methadone
• Certain antifungals (fluconazole)
• Antimalarials (chloroquine, hydroxychloroquine)
• The gastrointestinal drug cisapride Patients should inform all healthcare providers about their condition, maintain normal electrolyte levels (especially potassium, magnesium, and calcium), and consider regular ECG monitoring when starting new medications 1. Some medications may be used with caution at lower doses with appropriate monitoring if absolutely necessary, and concomitant treatment with more than one drug with the propensity of prolonging the QT interval should be avoided if possible 1. It is also important to note that hypokalaemia should be avoided during treatment with drugs capable of prolonging the QT interval, and the QT interval should be evaluated before initiation of treatment and during titration of dose 1. The QTc interval should be calculated by either of the two most standardised formulas, Bazett’s QT/(RR1/2) or Fridericia’s QT/ (RR1/3), and the comparative measurements during treatment should all utilise the same chosen method 1.

From the FDA Drug Label

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) Erythromycin should be avoided in patients with known prolongation of the QT interval, patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia, and in patients receiving Class IA (quinidine, procainamide) or Class III (dofetilide, amiodarone, sotalol) antiarrhythmic agents

Medications to Avoid in Patients with QT Interval Prolongation:

• 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)
• Other medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)
• Erythromycin, especially in patients with ongoing proarrhythmic conditions or those receiving Class IA or Class III antiarrhythmic agents 2 3

From the Research

Medications to Avoid in Patients with QT Interval Prolongation

• Antipsychotic drugs such as thioridazine, fluphenazine, haloperidol, quetiapine, risperidone, olanzapine, iloperidone, and ziprasidone, as they have been associated with QT interval prolongation 4, 5
• Antibiotics such as macrolide antibiotics (except azithromycin) and antifungal agents, as they can interact with other drugs to increase the risk of QT interval prolongation 6
• Antidepressants such as bupropion, duloxetine, fluoxetine, and paroxetine, as they can interact with other drugs to increase the risk of QT interval prolongation 6
• Cardiovascular drugs such as amiodarone, disopyramide, dofetilide, and pimozide, as they can interact with other drugs to increase the risk of QT interval prolongation 6
• Histamine H1-receptor antagonists, as they have been reported to prolong the QT interval 7

Alternative Medications

• For patients with psychosis and agitation, alternative medications such as aripiprazole, lurasidone, clozapine, and valproate may be considered, as they have a lower risk of QT interval prolongation 4
• For patients with a QTc interval of 500 ms or greater, medications such as aripiprazole, valproate, trazodone, and benzodiazepines may be used 4

Important Considerations

• Pharmacists play a crucial role in minimizing the risk of drug-induced QT interval prolongation by being aware of the medications that can cause QT interval prolongation and by monitoring patients for signs of QT interval prolongation 6
• Patients with risk factors for QT interval prolongation, such as congenital long QT syndrome, bradycardia, or heart disease, should be closely monitored for signs of QT interval prolongation 7
• Electrolyte imbalances, such as hypokalemia, hypomagnesemia, and hypocalcemia, should be corrected to reduce the risk of QT interval prolongation 6, 7