Which medications affect long QT syndrome?

Medications That Affect Long QT Syndrome

Multiple classes of medications can prolong the QT interval and potentially trigger life-threatening arrhythmias in patients with long QT syndrome, with antiarrhythmics, antipsychotics, antibiotics, and antiemetics being the highest risk categories. 1

High-Risk Medication Categories

Antiarrhythmic Drugs

• Class IA antiarrhythmics: Quinidine, procainamide, disopyramide (frequent QT prolongation) 1
• Class III antiarrhythmics: Sotalol, dofetilide, ibutilide (frequent QT prolongation) 1, 2
• Other antiarrhythmics: Amiodarone (less frequent but still significant risk) 1, 2

Antibiotics

• Macrolides: Clarithromycin, erythromycin, azithromycin 1, 3
• Fluoroquinolones: Ciprofloxacin, levofloxacin, moxifloxacin, sparfloxacin 1

Antipsychotics

• High risk: Thioridazine (25-30 ms QT prolongation), pimozide, ziprasidone (5-22 ms) 1, 4
• Moderate risk: Haloperidol, chlorpromazine, mesoridazine 1

Antiemetics

• Moderate to high risk: Domperidone, droperidol, ondansetron 1, 4

Other Notable QT-Prolonging Medications

• Antihistamines: Terfenadine, astemizole (now restricted in many countries) 1
• Antimalarials: Chloroquine, halofantrine 1
• Antidepressants: Tricyclic antidepressants, some SSRIs 5
• Opioid dependence agents: Methadone 1
• Gastrointestinal drugs: Cisapride 1

Risk Factors for Drug-Induced QT Prolongation

Several factors increase the risk of medication-induced QT prolongation:

1. Patient-specific factors:

   • Female gender
   • Advanced age (>65 years)
   • Congenital long QT syndrome
   • Cardiac disease (especially heart failure)
   • Bradycardia 1, 4

2. Metabolic factors:

   • Electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia)
   • Hepatic or renal dysfunction 1, 4

3. Drug-related factors:

   • High drug concentrations
   • Drug interactions (especially when combining multiple QT-prolonging drugs)
   • Rapid intravenous administration 1

Management Recommendations

1. For patients requiring QT-prolonging medications:

   • Obtain baseline ECG before initiating high-risk medications
   • Correct electrolyte abnormalities (maintain potassium >4 mM/L)
   • Avoid concomitant use of multiple QT-prolonging drugs 1, 4

2. For patients with drug-induced QT prolongation:

   • Immediate removal of the offending agent is indicated 1
   • Administer IV magnesium sulfate for episodes of torsades de pointes
   • Consider temporary pacing for recurrent torsades de pointes 1, 4

3. QTc monitoring thresholds:

   • High risk: >500 ms
   • Intermediate risk: 450-499 ms (males) or 470-499 ms (females)
   • Low risk: <450 ms (males) or <470 ms (females) 4

Common Pitfalls to Avoid

1. Failing to recognize drug interactions that potentiate QT prolongation
2. Overlooking electrolyte abnormalities, especially hypokalemia
3. Using amiodarone to treat torsades de pointes (potentially harmful in LQTS) 5
4. Administering Class IA antiarrhythmics (e.g., lidocaine, phenytoin) in patients with digitalis toxicity and severe ventricular arrhythmias 1
5. Using Bazett's formula at high heart rates (>80 bpm) instead of Fridericia's formula (QT/RR^1/3) 4

Special Considerations

• Amiodarone has a lower risk of inducing torsades de pointes compared to other Class III antiarrhythmics despite QT prolongation 1
• Concomitant use of CYP3A4 inhibitors (like azole antifungals) with QT-prolonging drugs can significantly increase the risk of arrhythmias 3
• Patients in intensive care units are particularly vulnerable to QT prolongation due to multiple risk factors and medication exposures 6

Understanding which medications affect long QT syndrome is crucial for preventing potentially fatal arrhythmias, particularly torsades de pointes, in susceptible patients.