Medications That Can Prolong QT Interval
Multiple medications can prolong the QT interval, including antiarrhythmics, antipsychotics, antibiotics, antiemetics, and antidepressants, all of which should be avoided or used with extreme caution in patients at risk for QT prolongation.
Common QT-Prolonging Medications by Class
Antiarrhythmics
Antibiotics
- Fluoroquinolones: moxifloxacin (highest risk), levofloxacin, ciprofloxacin (lowest risk) 1, 2
- Macrolides: erythromycin (highest risk), clarithromycin, azithromycin (lower risk) 3, 4
Antiemetics
Antipsychotics
Antidepressants
Other Medications
- Antimalarials: chloroquine, hydroxychloroquine 1
- Antifungals: ketoconazole, voriconazole, itraconazole, fluconazole 1
- Antiretrovirals: saquinavir 3
- Methadone 1
- Pentamidine 3
Risk Stratification of QT-Prolonging Medications
Highest Risk
- Antiarrhythmic drugs (Class IA and III): 1-10% incidence of Torsades de Pointes 1
- Moxifloxacin: greatest QT prolongation among fluoroquinolones 2
- Methadone 1
- Thioridazine and haloperidol 1
Moderate Risk
- Macrolide antibiotics (erythromycin > clarithromycin > azithromycin) 3, 4
- Levofloxacin, gemifloxacin 2
- Ondansetron and other 5-HT3 antagonists 3
Lower Risk
- Ciprofloxacin (lowest risk among fluoroquinolones) 2
- Azithromycin (lower risk than other macrolides) 3
Risk Factors for QT Prolongation
Several factors increase the risk of drug-induced QT prolongation:
- Female sex 3
- Advanced age (>65 years) 3
- Heart disease or bradyarrhythmias 3
- Electrolyte abnormalities (hypokalemia, hypomagnesemia) 1, 3
- Impaired hepatic/renal function 3
- Concomitant use of multiple QT-prolonging medications 3
- Baseline QT prolongation 1
Monitoring and Management
Baseline Assessment
- Obtain baseline ECG before starting QT-prolonging medications 1
- Check electrolytes (potassium, magnesium) 3
Ongoing Monitoring
- For high-risk medications like bedaquiline: ECG at baseline, 2 weeks, then monthly and after adding any new QT-prolonging medication 1
- Monitor electrolytes regularly 3
- Consider more frequent monitoring in ICU patients who are particularly vulnerable 6
QT Interval Classification
- Normal: <430 ms (males), <450 ms (females)
- Grade 1 prolongation: 450-480 ms
- Grade 2 prolongation: 481-500 ms
- Grade 3 prolongation: >501 ms 3
Safe Alternatives to QT-Prolonging Medications
Antiemetics
- Scopolamine (1.5 mg patch every 3 days)
- Antihistamines: meclizine, dimenhydrinate, diphenhydramine
- Trimethobenzamide, aprepitant, dexamethasone 3
Antibiotics
- When fluoroquinolones are necessary, ciprofloxacin has the lowest risk 2
- Consider non-macrolide, non-fluoroquinolone alternatives when possible
Important Precautions
- Avoid combinations of QT-prolonging drugs whenever possible 1, 3
- Correct electrolyte abnormalities before initiating QT-prolonging medications 3
- Discontinue the offending drug if QTc exceeds 500 ms or increases >60 ms from baseline 3, 5
- Use with extreme caution in patients with congenital long QT syndrome, history of Torsades de Pointes, or uncompensated heart failure 1, 5
- Consider drug interactions that may increase levels of QT-prolonging drugs (e.g., CYP inhibitors) 1
Common Pitfalls to Avoid
- Underestimating the risk of "safer" drugs - Even drugs considered safer (like ciprofloxacin) can cause QT prolongation in susceptible individuals 7
- Overlooking drug interactions - Combinations like levofloxacin with antidepressants can significantly increase QT prolongation risk 8
- Relying solely on automated ECG measurements of QTc interval 3
- Failing to account for multiple risk factors - The risk increases substantially when multiple factors are present 3
Remember that while the absolute risk of Torsades de Pointes with most non-antiarrhythmic drugs is low, the consequences can be fatal, making careful assessment and monitoring essential in patients receiving these medications.