What medications can cause QT (quantum time) interval prolongation?

Medications That Cause QT Prolongation

Multiple drug classes cause QT prolongation, with antiarrhythmics, antipsychotics, and certain antibiotics posing the highest risk—thioridazine (25-30 ms), Class IA/III antiarrhythmics, and macrolides like erythromycin represent the most dangerous agents requiring careful patient selection and monitoring. 1

High-Risk Antiarrhythmic Medications

Class IA and Class III antiarrhythmics carry the highest risk for QT prolongation and should be used with extreme caution:

• Class IA antiarrhythmics including quinidine, procainamide, and disopyramide cause significant QT prolongation 1
• Class III antiarrhythmics including sotalol, dofetilide, and ibutilide prolong the QT interval substantially 1
• Amiodarone causes marked 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 by Risk Level

Antipsychotics demonstrate a wide range of QT prolongation effects, requiring risk-stratified selection:

Highest Risk Antipsychotics

• Thioridazine causes 25-30 ms mean QTc prolongation with an FDA black box warning—this is the most dangerous antipsychotic for QT prolongation 1, 2
• Pimozide causes 13 ms mean QTc prolongation 2
• Ziprasidone causes 5-22 ms mean QTc prolongation 2

Moderate Risk Antipsychotics

• Clozapine causes 8-10 ms mean QTc prolongation 2
• Haloperidol causes 7 ms mean QTc prolongation, with dramatically higher risk via IV route compared to oral or IM administration 3, 2
• Quetiapine causes 6 ms mean QTc prolongation 2, 4

Lower Risk Antipsychotics

• Olanzapine causes only 2 ms mean QTc prolongation 2
• Risperidone causes 0-5 ms mean QTc prolongation 2
• Aripiprazole causes 0 ms mean QTc prolongation and should be preferred when QT concerns exist 1, 2

Antibiotic-Induced QT Prolongation

Macrolides and fluoroquinolones represent the highest-risk antibiotic classes:

Macrolide Antibiotics

• Erythromycin and clarithromycin carry the greatest overall risk among commonly used antibiotics, directly blocking the IKr potassium channel (HERG channel) in cardiac tissue 5
• Clarithromycin has a malignant arrhythmia risk of approximately 3 per million prescriptions 5
• Azithromycin causes dose-dependent QT prolongation with specific FDA warnings about torsades de pointes risk 3, 5

Fluoroquinolone Antibiotics

• Sparfloxacin carries the highest risk with 14.5 malignant arrhythmias per million prescriptions 5
• Moxifloxacin and levofloxacin cause QT prolongation with FDA warnings to avoid use in patients with known QT prolongation or uncorrected electrolyte abnormalities 3, 5
• Ciprofloxacin carries the lowest risk among fluoroquinolones (approximately 1 per million) and should be preferred if a fluoroquinolone is necessary 5

Other Antibiotics

• Trimethoprim-sulfamethoxazole causes QT prolongation through potassium channel blockade, with genetic polymorphisms significantly increasing individual susceptibility 3, 5

Cardiovascular and Other High-Risk Medications

Multiple non-psychiatric cardiovascular medications prolong QT:

• Cardiac medications: Adenosine, dopamine, epinephrine, dobutamine 3
• Antiemetics: Ondansetron, dolasetron, domperidone, droperidol 3, 1
• Antimalarials: Chloroquine, hydroxychloroquine, halofantrine 1
• Antifungals: Ketoconazole and other imidazole antimycotics 1
• Methadone causes significant QT prolongation, with nearly 1 million Americans using it—guidelines recommend pretreatment ECG, follow-up ECG within 30 days, and annual monitoring 1
• Antihistamines: Diphenhydramine, hydroxyzine, loratadine 3
• Respiratory medications: Albuterol, terbutaline, phenylephrine 3

Critical Risk Factors for Torsades de Pointes

Multiple patient-specific factors dramatically increase the risk of life-threatening arrhythmias:

• Female sex is a major risk factor for developing torsades de pointes 1, 2
• Age >65 years increases risk substantially 1
• Baseline QTc >500 ms or congenital long QT syndrome 1, 2
• Hypokalemia (K+ <4.5 mEq/L) or hypomagnesemia must be corrected before initiating QT-prolonging medications 1
• Bradycardia increases torsades risk 1
• Recent conversion from atrial fibrillation 1
• Congestive heart failure or left ventricular hypertrophy 1
• Concomitant use of multiple QT-prolonging drugs creates additive risk 3, 1
• Drug interactions that increase levels of QT-prolonging medications through CYP3A4 inhibition (azole antifungals, macrolides, protease inhibitors) 1

Monitoring and Management Algorithm

Systematic monitoring prevents life-threatening complications:

Before Initiating QT-Prolonging Medications

• Obtain baseline ECG to measure QTc interval in all patients 1, 2
• Check baseline electrolytes, particularly potassium and magnesium 1
• Review complete medication list for drug interactions 3
• Obtain detailed cardiac history including family history of sudden cardiac death 3

During Treatment

• Perform follow-up ECG after dose titration or within 30 days for high-risk medications like methadone 1, 2
• QTc >500 ms or increases >60 ms from baseline warrant immediate medication adjustment or discontinuation 1, 2
• Monitor electrolytes regularly, maintaining potassium >4.5 mEq/L 1

Management of QT Prolongation

• Immediately discontinue the offending agent when torsades de pointes is suspected 2
• Administer intravenous magnesium sulfate to suppress episodes of torsades de pointes even when serum magnesium is normal 1, 2
• Correct electrolyte abnormalities aggressively 2
• Consider temporary cardiac pacing for recurrent torsades de pointes after electrolyte repletion 2

Common Pitfalls and Critical Caveats

Route of administration matters critically—IV haloperidol dramatically increases torsades risk compared to oral or IM administration, despite similar QT prolongation 3, 2

Not all QT prolongation leads to torsades de pointes—amiodarone causes significant QT prolongation but has relatively lower torsades risk due to uniform repolarization effects 1

Genetic polymorphisms can increase susceptibility to drug-induced QT prolongation even in patients without baseline abnormalities, particularly with trimethoprim-sulfamethoxazole 5

Many non-cardiac medications cause QT prolongation—antihistamines, respiratory medications, and neurologic agents are frequently overlooked 3

Drug interactions significantly amplify risk—combining CYP3A4 inhibitors with amiodarone or quinidine is explicitly contraindicated due to severe overdose risk 1

QT prolongation risk is dose-dependent for most medications, requiring careful attention to dosing in high-risk patients 1