What medications can cause a prolonged QT (QTc) interval?

Medications That Cause QTc Interval Prolongation

Multiple medication classes can cause QTc prolongation, with antipsychotics, antiarrhythmics, antibiotics, and antimalarials posing the highest risk, particularly when used in combination or in patients with other risk factors.

High-Risk Medication Classes

Antipsychotics

• First-generation antipsychotics:

  • Thioridazine (25-30 ms prolongation) 1
  • Haloperidol (7 ms prolongation) 1, 2
  • Pimozide (13 ms prolongation) 1
  • Chlorpromazine (significant QTc prolongation) 3

• Second-generation antipsychotics:

  • Ziprasidone (5-22 ms prolongation) 1
  • Quetiapine (6 ms prolongation) 1, 4
  • Clozapine (8-10 ms prolongation) 1
  • Lower risk options: Aripiprazole (0 ms), Olanzapine (2 ms), Risperidone (0-5 ms) 1

Antiarrhythmics

• Class IA: Quinidine, Procainamide 5, 6
• Class III: Amiodarone, Sotalol 6

Antibiotics

• Macrolides: Clarithromycin 5
• Fluoroquinolones:
  • Sparfloxacin (highest risk)
  • Levofloxacin 7
  • Moxifloxacin 4
  • Gatifloxacin 4
• Other antibiotics: Trimethoprim-sulfamethoxazole 5

Antimalarials

• Halofantrine
• Chloroquine
• Quinine 5

Other Medications

• Antiemetics: Ondansetron 8
• Antiviral drugs: Amantadine 5
• Antifungals: Ketoconazole and other azoles 5, 6
• Antiparasitic drugs: Pentamidine 5, 4
• Opioids: Methadone, Levomethadyl acetate 4

Risk Stratification

High-Risk Features for QTc Prolongation

1. Baseline QTc >450 ms (males) or >470 ms (females) 1
2. QTc >500 ms (high-risk category) 1
3. Increase of >60 ms from baseline QTc 1
4. Female sex 1, 2
5. Advanced age (>65 years) 1, 9
6. Underlying heart disease 1
7. Bradyarrhythmias 1
8. Electrolyte abnormalities (hypokalemia, hypomagnesemia) 1, 4
9. Concomitant use of multiple QT-prolonging medications 1, 4
10. Genetic predisposition to QT prolongation 5, 10

Monitoring and Management

Baseline Assessment

• Obtain baseline ECG before starting QT-prolonging medications 1
• Assess electrolyte levels (potassium, magnesium) 1
• Review medication list for potential drug interactions 1

Ongoing Monitoring

• Repeat ECG 7 days after initiation of QT-prolonging therapy 1
• Perform additional ECGs following any dosing changes 1
• Manually measure QT interval rather than relying on automated readings 1
• Maintain serum potassium between 4.5-5 mEq/L 1

Management of QTc Prolongation

• For QTc >500 ms: Discontinue offending QT-prolonging medications 1
• For QTc 470-500 ms (females) or 450-500 ms (males): Consider dose reduction or discontinuation 1
• Correct electrolyte abnormalities 1
• For Torsades de Pointes: Administer 2g IV magnesium sulfate regardless of serum magnesium level 1

Special Considerations

Drug Combinations to Avoid

• Multiple QT-prolonging drugs simultaneously 4, 6
• QT-prolonging drugs with cytochrome P450 inhibitors (e.g., macrolide antibiotics, imidazole antifungals) 5
• QT-prolonging drugs in patients taking diuretics (risk of electrolyte abnormalities) 6

Vulnerable Populations

• Elderly patients (>65 years) 1, 9
• Females (higher baseline QTc) 1, 2
• Patients with cardiovascular disease 1
• Patients with genetic polymorphisms affecting drug metabolism 5
• ICU patients (multiple risk factors) 8

Common Pitfalls

• Relying on automated ECG readings for QTc measurement 1
• Neglecting to monitor electrolytes regularly 1
• Failing to recognize drug-drug interactions that increase QT risk 6
• Not considering cumulative risk when multiple risk factors are present 10
• Overlooking the need for ECG monitoring after dose changes 1

By understanding which medications pose QTc prolongation risk and implementing appropriate monitoring strategies, clinicians can minimize the risk of potentially fatal arrhythmias like Torsades de Pointes.