What medications can cause a prolonged QT (Quantitative T) interval?

From the Guidelines

Medications that can cause prolongation of the QT interval include antiarrhythmics, antibiotics, antipsychotics, antidepressants, and antiemetics, and removal of the offending agent is indicated in patients with drug-induced long QT syndrome 1. The list of medications that can cause QT prolongation is extensive and includes:

• Antiarrhythmics such as disopyramide, dofetilide, ibutilide, procainamide, quinidine, and sotalol 1
• Antibiotics like clarithromycin, erythromycin, halofantrine, pentamidine, and sparfloxacin 1
• Antipsychotics including chlorpromazine, haloperidol, mesoridazine, thioridazine, and pimozide 1
• Antiemetics like domperidone and droperidol 1
• Opioid dependence agents such as methadone 1
• Other medications like amiodarone, arsenic trioxide, bepridil, and cisapride 1 These medications can cause QT prolongation by blocking potassium channels in cardiac cells, delaying ventricular repolarization, and increasing the risk of potentially fatal arrhythmias like Torsades de Pointes 1. Risk factors that compound this effect include:
• Electrolyte abnormalities, especially hypokalemia and hypomagnesemia 1
• Female gender 1
• Bradycardia 1
• Recent conversion from atrial fibrillation 1
• Congestive heart failure 1
• Digitalis therapy 1
• High drug concentrations, often due to drug interactions 1
• Rapid rate of intravenous drug administration 1
• Baseline QT prolongation 1
• Ventricular arrhythmia 1
• Left ventricular hypertrophy 1
• Congenital long QT syndrome 1
• Certain DNA polymorphisms 1
• Concomitant use of two or more drugs that prolong the QT interval 1 In patients with drug-induced long QT syndrome, removal of the offending agent is indicated, and intravenous magnesium can suppress episodes of torsades de pointes without necessarily shortening QT, even when serum magnesium is normal 1.

From the FDA Drug Label

1. 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)] .
2. 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 In general, elderly patients may be more susceptible to drug-associated effects on the QT interval. Therefore, precaution should be taken when using Ciprofloxacin Tablets USP 250 mg, 500 mg and 750 mg 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 caused prolonged QTc are:

• Quetiapine 2
• Clarithromycin 3
• Ciprofloxacin 4

Key points to consider:

• QT prolongation can be a serious side effect of these medications
• Elderly patients may be more susceptible to drug-associated effects on the QT interval
• Concomitant use of other drugs that can prolong the QT interval should be avoided
• Risk factors for torsade de pointes, such as uncorrected hypokalemia, should be carefully monitored.

From the Research

Medications that Cause Prolonged QTc Interval

The following medications have been associated with a prolonged QTc interval:

• Antipsychotic drugs, such as:
  • Haloperidol, which can cause QTc prolongation ranging from 4-6 ms 5, 6, 7, 8, 9
  • Thioridazine, which can cause QTc prolongation of up to 35 ms 5, 7, 8
  • Olanzapine, which can cause QTc prolongation ranging from 4-6 ms 5, 7, 8
  • Quetiapine, which can cause QTc prolongation and is associated with an increased risk of ventricular arrhythmias and sudden cardiac death 8, 9
  • Risperidone, which can cause QTc prolongation of up to 4 ms 7, 8
  • Ziprasidone, which can cause QTc prolongation and has been associated with cases of TdP 8
• Antidepressants, such as:
  • Amitriptyline, imipramine, doxepin, and trazadone, which can depress the delayed rectifier potassium current (IKr) in a dose-dependent manner 8
  • Fluoxetine, which has been associated with QTc prolongation but no cases of TdP have been reported 8

Risk Factors for QTc Prolongation

The following risk factors can increase the likelihood of QTc prolongation:

• Female gender 7, 8
• Old age 6, 8, 9
• Congestive heart failure 7, 8, 9
• Hypokalemia 5, 6, 7, 8, 9
• Hypomagnesemia 7
• Bradycardia 7, 8
• Concomitant use of other QTc-prolonging drugs 5, 6, 7, 8, 9
• Substance abuse 8
• Electrolyte disorders 8
• Anorexia nervosa 8
• Congenital Long QT syndrome 8