Medications That Can Lengthen QT Interval
Many medication classes can prolong the QT interval, with antiarrhythmics, antipsychotics, and certain antibiotics posing the highest risk for QT prolongation and potentially fatal torsades de pointes. 1
High-Risk Medications (Frequent QT Prolongation)
Antiarrhythmic Medications
- Class IA antiarrhythmics: quinidine, procainamide, disopyramide 2
- Class III antiarrhythmics: sotalol, dofetilide, ibutilide 2
- Amiodarone (causes marked QT prolongation but has relatively lower risk of torsades de pointes compared to other antiarrhythmics) 2, 1
Antipsychotics
- Thioridazine, haloperidol, chlorpromazine, pimozide 2, 3
- Other antipsychotics like quetiapine also carry risk, though generally lower than first-generation agents 4, 5
- Ziprasidone and iloperidone have higher risk, while aripiprazole and lurasidone have minimal risk 6
Antimicrobial Agents
- Macrolide antibiotics: clarithromycin, erythromycin, azithromycin 2, 1
- Fluoroquinolones: sparfloxacin, moxifloxacin, levofloxacin, ciprofloxacin 2, 7
- Antifungals: ketoconazole and other imidazole antimycotics 2, 1
- Antimalarials: chloroquine, hydroxychloroquine, halofantrine 2, 1
- Pentamidine (used for Pneumocystis pneumonia) 2
Other Medications
- Antiemetics: ondansetron, dolasetron, domperidone, droperidol 2
- Methadone 2
- Cisapride (withdrawn from US market due to QT prolongation) 2
Risk Factors for Torsades de Pointes
The risk of developing torsades de pointes is significantly increased with:
- Female gender 2, 3
- Hypokalemia or hypomagnesemia 2, 8
- Bradycardia 2
- Recent conversion from atrial fibrillation 2
- Congestive heart failure 2
- Baseline QT prolongation or congenital long QT syndrome 2
- Advanced age 1, 7
- Renal or hepatic dysfunction 8, 7
- Concomitant use of multiple QT-prolonging drugs 2, 9
- Drug interactions that increase levels of QT-prolonging medications 2
Monitoring and Management
- Baseline ECG is recommended before starting QT-prolonging medications 1
- QTc intervals >500 ms or increases >60 ms from baseline warrant immediate attention 1
- Electrolyte monitoring (especially potassium and magnesium) is essential 2, 1
- In patients with drug-induced LQTS, removal of the offending agent is indicated 2
- For patients requiring QT-prolonging medications, consider alternatives with lower risk when possible 1
- Intravenous magnesium can suppress episodes of torsades de pointes even when serum magnesium is normal 2
Special Considerations
- Combination therapy significantly increases risk - antipsychotics plus antidepressants showed greater QT prolongation than antipsychotic monotherapy 9
- ICU patients are particularly vulnerable due to multiple risk factors and exposure to multiple QT-prolonging medications 10
- Elderly patients may be more susceptible to drug-associated effects on the QT interval due to reduced renal function and other comorbidities 7
- Genetic polymorphisms can increase susceptibility to drug-induced QT prolongation 2
Common Pitfalls and Caveats
- Not all QT prolongation leads to torsades de pointes - the risk varies by medication 2
- Amiodarone causes significant QT prolongation but has a relatively lower risk of torsades de pointes compared to other antiarrhythmics 1
- Many medications not primarily prescribed for cardiac conditions can cause QT prolongation 2
- Drug interactions can significantly increase the risk - always check for potential interactions when prescribing multiple medications 2
- QT prolongation risk is dose-dependent for most medications 2