What medications can cause QT (quantum time) interval prolongation in patients, especially those with a history of cardiovascular disease?

Medications That Cause QT Prolongation

High-Risk Drug Categories

The most clinically significant QT-prolonging medications include Class IA and III antiarrhythmics, certain antipsychotics (particularly thioridazine and IV haloperidol), macrolide antibiotics, fluoroquinolones, and specific antiemetics—all of which require baseline ECG monitoring and careful risk stratification before initiation. 1

Antiarrhythmic Medications

• Class IA antiarrhythmics (quinidine, procainamide, disopyramide) carry high risk and should be used with extreme caution 1
• Class III antiarrhythmics (sotalol, dofetilide, ibutilide) cause significant QT prolongation 1
• Amiodarone causes marked QT prolongation (often >40 ms) but paradoxically has lower torsades de pointes risk due to uniform repolarization delay across all myocardial layers 1
• Verapamil and diltiazem prolong PR interval through AV nodal blockade and create additive risk when combined with QTc-prolonging drugs 1

Antipsychotic Medications (Ranked by Risk)

• Thioridazine: 25-30 ms mean QTc prolongation with FDA black box warning—highest risk antipsychotic 1, 2
• Pimozide: 13 ms mean QTc prolongation 2
• Ziprasidone: 5-22 ms mean QTc prolongation 2
• Clozapine: 8-10 ms mean QTc prolongation 2
• IV Haloperidol: 7 ms mean QTc prolongation, dramatically higher risk than oral/IM routes 1, 2
• Quetiapine: 6 ms mean QTc prolongation 2, 3
• Olanzapine: 2 ms mean QTc prolongation—minimal risk 2
• Risperidone: 0-5 ms mean QTc prolongation 2
• Aripiprazole: 0 ms mean QTc prolongation—safest option 1, 2

Antimicrobial Agents

Macrolide Antibiotics:

• Clarithromycin, erythromycin (especially IV), and azithromycin all prolong QT interval with FDA warnings 1, 4, 5
• Erythromycin carries highest risk among macrolides, particularly with IV administration 6, 5
• Clarithromycin is contraindicated with cisapride or pimozide due to fatal arrhythmia risk 4

Fluoroquinolone Antibiotics:

• Sparfloxacin, moxifloxacin, levofloxacin, and ciprofloxacin cause QT prolongation 1
• Moxifloxacin causes more common QTc prolongation in hypokalaemia and proarrhythmic conditions 6
• Gatifloxacin carries significant risk 5

Antifungal Agents:

• Ketoconazole and other imidazole antimycotics prolong QT interval 1

Antimalarial Drugs:

• Chloroquine, hydroxychloroquine, mefloquine, quinine, and halofantrine cause QT prolongation 6, 1

Other Antimicrobials:

• Pentamidine (used for Pneumocystis pneumonia) significantly prolongs QT interval 6, 1

Antiemetic Medications

• 5-HT3 antagonists (ondansetron, granisetron, dolasetron) carry FDA warnings for QT prolongation 6, 1, 7
• Metoclopramide prolongs QT interval and should be used with extreme caution 6, 7
• Domperidone prolongs QTc and should be avoided entirely in at-risk patients 6, 7
• Droperidol causes QT prolongation 1
• Prochlorperazine is contraindicated when combined with other QT-prolonging medications 7

Antidepressants

• Tricyclic antidepressants (amitriptyline) cause mean QT prolongation of 24 ms, particularly dangerous in overdose 1
• Citalopram and escitalopram can prolong QT in patients with pre-existing cardiovascular disease 1

Other High-Risk Medications

• Methadone carries high risk with nearly 1 million Americans exposed; requires pretreatment ECG, 30-day follow-up ECG, and annual monitoring 1
• Cisapride (withdrawn from US market) causes QT prolongation 1
• Antivirals: Saquinavir increases ventricular arrhythmia risk 6

Critical Risk Factors for Torsades de Pointes

Patient-specific risk factors that exponentially increase arrhythmia risk include: 1

• Female sex—major independent risk factor 1, 7
• Age >65 years 1, 7
• Hypokalemia (especially K+ <4.5 mEq/L) or hypomagnesemia 1, 7
• Baseline QTc >500 ms or congenital long QT syndrome 1, 2
• Bradycardia 1
• Recent conversion from atrial fibrillation 1
• Congestive heart failure or left ventricular hypertrophy 1
• Concomitant use of multiple QT-prolonging drugs—creates additive/synergistic risk 1, 2
• Drug interactions increasing levels of QT-prolonging medications (particularly CYP3A4 inhibitors) 1, 4
• Genetic polymorphisms increasing susceptibility 1

Mandatory Monitoring Protocol

Baseline Assessment:

• Obtain ECG before starting any QT-prolonging medication to measure baseline QTc 1, 2, 7
• Check potassium (maintain >4.5 mEq/L), magnesium, and correct all electrolyte abnormalities before initiation 1, 7
• Review complete medication list for drug interactions and discontinue other QT-prolonging agents when possible 1, 7
• Obtain detailed cardiac history including family history of sudden cardiac death 1

Follow-up Monitoring:

• Repeat ECG 7-15 days after initiation or dose changes, then monthly during first 3 months 7
• For high-risk medications (methadone, IV haloperidol >5 mg), perform ECG within 30 days 1
• For IV haloperidol doses >5 mg or cumulative doses ≥100 mg, implement continuous telemetry monitoring 1

Action Thresholds:

• QTc >500 ms or increase >60 ms from baseline: Immediately discontinue medication and consider safer alternatives 1, 2, 7
• QTc 420-499 ms: Use extreme caution, avoid combining multiple QT-prolonging drugs, intensify monitoring 1

Management of Drug-Induced Torsades de Pointes

Immediate interventions when torsades occurs: 1, 7

1. Discontinue offending agent immediately 1
2. Administer IV magnesium sulfate 2g as first-line therapy, even if serum magnesium is normal 1, 7
3. Correct electrolytes: potassium to >4.5 mEq/L, normalize magnesium 1, 7
4. Non-synchronized defibrillation if sustained ventricular arrhythmias with hemodynamic instability 7
5. Temporary cardiac pacing is highly effective for recurrent episodes after electrolyte correction 1
6. Isoproterenol may be considered if pacing unavailable 1

Safer Alternatives by Clinical Scenario

For Agitation/Delirium:

• First-line: Aripiprazole (0 ms QTc prolongation) 2
• Second-line: Olanzapine (2 ms QTc prolongation) 2
• Avoid: Thioridazine, ziprasidone, IV haloperidol 2
• Route matters: Prefer oral or IM haloperidol over IV when haloperidol is necessary 1, 2

For Nausea/Vomiting in Patients with QT Prolongation:

• First-line: Antihistamines (meclizine, dimenhydrinate, diphenhydramine)—safest options 7
• Alternative: Scopolamine transdermal patch 7
• Avoid entirely: All 5-HT3 antagonists, metoclopramide, domperidone, prochlorperazine 7

For Infections:

• Consider azithromycin risk vs. benefit; use shortest effective duration 1
• Avoid combining macrolides with other QT-prolonging drugs 5
• Monitor closely if fluoroquinolones necessary in high-risk patients 6, 1

Critical Pitfalls to Avoid

• Do not use amiodarone to treat polymorphic VT in drug-induced LQTS—it worsens the underlying problem despite being effective for other VT types 8
• IV administration dramatically increases risk compared to oral/IM routes, particularly for haloperidol 1, 2
• Not all QT prolongation leads to torsades—risk varies significantly by medication, with amiodarone causing marked prolongation but relatively lower torsades risk 1
• Combining multiple QT-prolonging drugs exponentially increases risk, not just additively 1, 2
• QT prolongation is dose-dependent for most medications 1
• Many non-cardiac medications (antibiotics, antiemetics, antipsychotics) cause significant QT prolongation—always check complete medication list 1, 7
• Genetic vulnerabilities exist—some patients have polymorphisms increasing susceptibility to drug-induced QT prolongation 1