What medications can cause prolonged QT intervals?

Medications That Cause Prolonged QT Intervals

Numerous medications can cause QT interval prolongation, with antiarrhythmic drugs posing the highest risk (1-10% incidence of torsades de pointes), while non-antiarrhythmic drugs generally carry lower but still significant risk. 1

High-Risk Medications (Frequent QT Prolongation)

Antiarrhythmic Drugs

• Class IA antiarrhythmics:

  • Disopyramide
  • Procainamide
  • Quinidine

• Class III antiarrhythmics:

  • Dofetilide
  • Ibutilide
  • Sotalol
  • Amiodarone (less frequent but still significant)

Moderate-Risk Medications (Less Frequent QT Prolongation)

Antibiotics/Anti-infectives

• Macrolides:
  • Clarithromycin
  • Erythromycin
• Fluoroquinolones:
  • Sparfloxacin
  • Moxifloxacin
• Other anti-infectives:
  • Pentamidine
  • Trimethoprim-sulfamethoxazole

Antipsychotics

• Chlorpromazine
• Haloperidol
• Thioridazine
• Pimozide
• Mesoridazine

Antiemetics

• Domperidone
• Droperidol

Opioid Dependence Agents

• Methadone

Other Notable Agents

• Arsenic trioxide
• Bepridil
• Cisapride
• Antimalarial drugs (halofantrine, chloroquine)
• Azole antifungals (particularly when combined with other QT-prolonging drugs)

Risk Factors for Torsades de Pointes

When prescribing QT-prolonging medications, consider these risk factors that increase the likelihood of developing torsades de pointes 1:

1. Patient-specific factors:

   • Female gender
   • Advanced age
   • Congenital long QT syndrome
   • Heart disease (especially left ventricular hypertrophy, ischemia, low ejection fraction)
   • Bradycardia
   • Electrolyte abnormalities (hypokalemia, hypomagnesemia, hypocalcemia)

2. Medication-related factors:

   • High drug concentrations (except quinidine)
   • Drug interactions (especially CYP3A4 inhibitors with QT-prolonging drugs)
   • Rapid IV administration
   • Concomitant use of multiple QT-prolonging drugs

Monitoring Recommendations

For patients receiving QT-prolonging medications:

1. Baseline assessment:

   • ECG with QTc measurement before starting therapy
   • Electrolyte panel (potassium, magnesium, calcium)
   • Review of concomitant medications

2. Ongoing monitoring:

   • ECG monitoring after initiation and dose increases
   • For high-risk antiarrhythmics (quinidine, procainamide, disopyramide, sotalol, dofetilide): 48-72 hours of monitoring
   • For ibutilide: 4-5 hours of monitoring
   • Document QTc in medical record at least every 8 hours during monitoring periods 1

3. Warning signs requiring immediate attention:

   • QTc >500 ms or increase of >60 ms from baseline
   • New bradycardia
   • Dizziness or syncope
   • T-wave alternans or polymorphic ventricular premature beats

Management of QT Prolongation

If significant QT prolongation occurs:

1. Discontinue the offending agent - this is a Class I recommendation 1
2. Correct electrolyte abnormalities (especially potassium >4 mEq/L)
3. Consider temporary pacing for recurrent torsades de pointes
4. Administer IV magnesium even if serum magnesium is normal

Special Considerations

• Drug interactions: Many QT-prolonging drugs are metabolized by CYP3A4. Inhibitors of this enzyme (ketoconazole, itraconazole, clarithromycin) can dramatically increase drug levels and QT risk 1, 2

• Amiodarone paradox: Despite causing marked QT prolongation, amiodarone has a relatively low incidence of torsades de pointes compared to other QT-prolonging antiarrhythmics 1

• Bedaquiline interactions: Avoid combining with other QT-prolonging drugs; requires ECG monitoring at baseline, 2 weeks, then monthly and after adding any new medication known to prolong QT 1

Always check updated resources like www.crediblemeds.org for the most current list of QT-prolonging medications, as this list continues to evolve with new evidence.