What drugs can cause prolonged QT intervals?

Drugs That Cause QT Prolongation

Multiple drug classes can prolong the QT interval, with antiarrhythmics, certain antipsychotics (especially thioridazine and haloperidol IV), macrolide antibiotics, fluoroquinolones, and methadone posing the highest risk for torsades de pointes. 1

High-Risk Antiarrhythmic Medications

Class IA and III antiarrhythmics carry the most significant risk:

• Class IA antiarrhythmics (quinidine, procainamide, disopyramide) should be used with extreme caution due to substantial QT prolongation risk 1
• Class III antiarrhythmics (sotalol, dofetilide, ibutilide) cause marked QT prolongation 1
• Amiodarone causes significant QT prolongation but paradoxically has a relatively lower risk of torsades de pointes compared to other antiarrhythmics due to uniform repolarization delay across all myocardial layers 1

Antipsychotic Medications (Ranked by Risk)

The degree of QT prolongation varies dramatically among antipsychotics:

• Thioridazine: 25-30 ms mean prolongation with FDA black box warning—highest risk 2
• Pimozide: 13 ms mean prolongation 2
• Ziprasidone: 5-22 ms mean prolongation 2
• Clozapine: 8-10 ms mean prolongation 2
• Haloperidol: 7 ms mean prolongation, with dramatically higher risk via IV route compared to oral or IM administration 1, 2
• Quetiapine: 6 ms mean prolongation 2, 3
• Risperidone: 0-5 ms mean prolongation 2
• Olanzapine: 2 ms mean prolongation—very low risk 2
• Aripiprazole and brexpiprazole: 0 ms mean prolongation—preferred when QT concerns exist 2

Critical caveat: IV haloperidol carries substantially higher torsades risk than oral or IM routes despite similar QT prolongation 1, 2

Antimicrobial Agents

Multiple antibiotic classes prolong QT:

• Macrolides: clarithromycin, erythromycin, azithromycin 1
• Fluoroquinolones: sparfloxacin, moxifloxacin, levofloxacin, ciprofloxacin 1
• Antifungals: ketoconazole and other imidazole antimycotics 1
• Antimalarials: chloroquine, hydroxychloroquine, halofantrine 1
• Pentamidine (for Pneumocystis pneumonia) 1

Gastrointestinal and Antiemetic Medications

• Ondansetron, dolasetron, domperidone, droperidol 1
• Metoclopramide (lower risk than high-risk medications but requires monitoring) 4
• Cisapride (withdrawn from US market) 1

Other High-Risk Medications

• Methadone poses significant QT risk—guidelines recommend pretreatment ECG, follow-up within 30 days, and annual monitoring 1
• Tricyclic antidepressants (especially amitriptyline) cause more QT prolongation than SSRIs, particularly in overdose (24 ms vs -1 ms) 1
• Citalopram and escitalopram can prolong QT in patients with pre-existing cardiovascular disease 1

Critical Risk Factors for Torsades de Pointes

These factors exponentially increase risk when combined with QT-prolonging drugs:

• Female gender 1, 4
• Age >65 years 1
• Hypokalemia (especially <4.5 mEq/L) or hypomagnesemia 1, 4
• Bradycardia 1
• Baseline QTc >500 ms or congenital long QT syndrome 1, 4
• Congestive heart failure or left ventricular hypertrophy 1
• Recent conversion from atrial fibrillation 1
• Concomitant use of multiple QT-prolonging drugs 1, 4
• Drug interactions increasing levels of QT-prolonging medications (especially CYP3A4 inhibitors with amiodarone or quinidine) 1

Monitoring Recommendations

Systematic ECG surveillance is essential:

• Obtain baseline ECG before initiating any QT-prolonging medication 1, 4
• Repeat ECG 7 days after starting therapy and after any dose change 4
• QTc >500 ms or increase >60 ms from baseline warrants immediate attention—adjust dose or discontinue medication 1, 4
• Correct electrolyte abnormalities (potassium >4.5 mEq/L, replete magnesium) before initiating therapy 1
• IV administration carries higher risk than oral dosing due to greater cardiac drug exposure and rapid infusion rates 1

Management of Drug-Induced QT Prolongation

When QTc becomes dangerously prolonged:

• Immediately discontinue the offending agent 1, 4
• Administer IV magnesium sulfate 2g as first-line therapy for torsades de pointes, regardless of serum magnesium level 4
• Correct all electrolyte abnormalities (potassium, magnesium, calcium) 1
• Consider temporary cardiac pacing for recurrent torsades after electrolyte repletion 1
• Isoproterenol IV (titrated to heart rate >90 bpm) when temporary pacemaker not immediately available 4

Common Pitfalls

• Not all QT prolongation leads to torsades de pointes—risk varies substantially by medication 1
• Route of administration matters critically—IV haloperidol has dramatically higher arrhythmia risk than oral/IM 1, 2
• Drug interactions can be more dangerous than individual drugs—combining CYP3A4 inhibitors (azole antifungals, macrolides, protease inhibitors) with amiodarone or quinidine is contraindicated 1
• Many non-cardiac medications cause QT prolongation—maintain high index of suspicion across all drug classes 1
• Women face higher risk of torsades de pointes with antipsychotics and other QT-prolonging drugs 2
• Genetic polymorphisms can increase susceptibility to drug-induced QT prolongation 1