What medications can prolong the QTc (QT corrected) interval?

Medications That Prolong the QTc Interval

Multiple drug classes can prolong the QTc interval, with antiarrhythmics, antipsychotics, certain antibiotics, and antiemetics posing the highest risk—thioridazine (25-30 ms), Class IA and III antiarrhythmics, and IV haloperidol require particular caution. 1

High-Risk Antiarrhythmic Medications

Class IA antiarrhythmics cause significant QTc prolongation and should be used with extreme caution: 1

• Quinidine 1
• Procainamide 1
• Disopyramide 1

Class III antiarrhythmics are among the most potent QTc-prolonging agents: 1

• Sotalol 1
• Dofetilide 1
• Ibutilide 1
• Amiodarone - causes marked QTc prolongation but paradoxically has relatively lower torsades de pointes risk due to uniform repolarization delay across myocardial layers 1

Antipsychotic Medications (Ranked by QTc Prolongation Risk)

Highest risk antipsychotics that should be avoided when possible: 2

• Thioridazine: 25-30 ms prolongation with FDA black box warning 2
• Pimozide: 13 ms prolongation 2
• Ziprasidone: 5-22 ms prolongation 2

Moderate risk antipsychotics: 2

• Clozapine: 8-10 ms prolongation 2
• Haloperidol: 7 ms prolongation (dramatically higher risk with IV route versus oral/IM) 1, 2
• Quetiapine: 6 ms prolongation 2, 3

Lower risk antipsychotics: 2

• Olanzapine: 2 ms prolongation 2
• Risperidone: 0-5 ms prolongation 2
• Aripiprazole: 0 ms prolongation (preferred when QTc is a concern) 2

Additional antipsychotics with QTc risk: 1

• Chlorpromazine 1

Antimicrobial Agents

Macrolide antibiotics pose significant QTc risk: 1

• Clarithromycin 1
• Erythromycin 1
• Azithromycin (dose-dependent with FDA warnings for torsades de pointes) 1

Fluoroquinolones can prolong QTc: 1

• Moxifloxacin 1
• Levofloxacin 1
• Ciprofloxacin 1
• Sparfloxacin 1
• Gatifloxacin 3

Antifungal agents: 1

• Ketoconazole and other imidazole antimycotics 1

Antimalarial drugs: 1, 4

• Chloroquine 1
• Hydroxychloroquine (FDA label explicitly warns against use with other QTc-prolonging drugs) 4
• Halofantrine 1

Other antimicrobials: 1

• Pentamidine (used for Pneumocystis pneumonia) 1
• Trimethoprim-sulfamethoxazole (via potassium channel blockade) 1

Antiemetic Medications

5-HT3 receptor antagonists carry FDA warnings for QTc prolongation and should be avoided in high-risk patients: 5

• Ondansetron 1, 5
• Dolasetron 1, 5
• Granisetron 5

Other antiemetics with QTc risk: 1, 5

• Domperidone 1, 5
• Droperidol (FDA black box warning) 1, 5
• Metoclopramide (use with extreme caution only) 5
• Prochlorperazine (contraindicated with other QTc-prolonging medications) 5

Opioids and Pain Medications

• Methadone - requires pretreatment ECG, follow-up within 30 days, and annual monitoring 1
• Levomethadyl acetate 3

Gastrointestinal Medications

• Cisapride (withdrawn from US market) 1

Cardiovascular Medications

Sympathomimetics and vasopressors: 1

• Adenosine 1
• Dopamine 1
• Epinephrine 1
• Dobutamine 1

Respiratory Medications

• Albuterol 1
• Terbutaline 1
• Phenylephrine 1

Antihistamines

• Diphenhydramine 1
• Hydroxyzine 1
• Loratadine 1

Antidepressants

• Citalopram and escitalopram (particularly in patients with pre-existing cardiovascular disease) 1
• Tricyclic antidepressants (especially amitriptyline in overdose, causing 24 ms prolongation versus -1 ms with SSRIs) 1

Critical Risk Factors for Torsades de Pointes

Patient-specific factors that dramatically increase risk: 1, 2

• Female gender 1, 2
• Age >65 years 1, 2
• Baseline QTc >500 ms or increases >60 ms from baseline 1, 2
• Hypokalemia (especially <4.5 mEq/L) or hypomagnesemia 1, 2
• Bradycardia 1, 2
• Recent conversion from atrial fibrillation 1
• Congestive heart failure 1, 2
• Congenital long QT syndrome 1, 2
• Concomitant use of multiple QTc-prolonging drugs 1, 2
• Drug interactions increasing levels of QTc-prolonging medications (especially CYP3A4 inhibitors) 1

Essential Monitoring Requirements

Baseline assessment before initiating any QTc-prolonging medication: 1, 2

• Obtain baseline ECG to measure QTc interval 1, 2
• Check electrolytes, maintaining potassium >4.5 mEq/L and normalizing magnesium 1, 2, 5
• Review complete medication list for drug interactions 1
• Obtain detailed cardiac history including family history of sudden cardiac death 1

Follow-up monitoring: 1, 2

• Repeat ECG within 7-30 days after starting therapy or dose changes 1, 2
• QTc >500 ms or increases >60 ms from baseline warrant immediate attention and medication adjustment 1, 2
• Regular electrolyte monitoring throughout treatment 1, 2

Management of Drug-Induced QTc Prolongation

Immediate interventions when QTc prolongation is identified: 1, 2

• Remove the offending agent immediately 1, 2
• Correct electrolyte abnormalities (potassium >4.5 mEq/L, normalize magnesium) 1, 2
• Administer intravenous magnesium sulfate (2g) for torsades de pointes even if serum magnesium is normal 1, 2
• Consider temporary cardiac pacing for recurrent torsades de pointes 1, 2
• Isoproterenol may be used if pacing unavailable 2

Critical Pitfalls to Avoid

Route of administration matters significantly: 1, 2

• IV haloperidol carries dramatically higher torsades risk than oral or IM routes 1, 2
• Rapid IV infusion increases cardiac drug exposure and risk 1

Drug interactions create multiplicative risk: 1

• CYP3A4 inhibitors (azole antifungals, macrolides, protease inhibitors) with amiodarone or quinidine dramatically increase levels 1
• Ketoconazole with amiodarone is contraindicated 1

Not all QTc prolongation carries equal torsades risk: 1

• Amiodarone causes significant QTc prolongation but has relatively lower torsades risk 1
• Risk is dose-dependent for most medications 1

Genetic polymorphisms increase individual susceptibility to drug-induced QTc prolongation 1