What medications can cause QT (QT interval) prolongation?

QT Prolongation Medications

High-Risk Antiarrhythmic Drugs

Class IA and Class III antiarrhythmic agents represent the highest-risk medications for QT prolongation and should be used with extreme caution, requiring mandatory ECG monitoring. 1, 2

• Class IA antiarrhythmics (quinidine, procainamide, disopyramide) prolong the QT interval through potassium channel blockade and carry significant risk of torsades de pointes 1, 2, 3
• Class III antiarrhythmics (sotalol, dofetilide, ibutilide) are specifically designed to prolong repolarization and have well-documented arrhythmia risk 1, 2, 3
• Amiodarone causes marked QT prolongation (often >60 ms) but paradoxically has a relatively lower risk of torsades de pointes compared to other antiarrhythmics due to uniform repolarization delay across all myocardial layers 2, 3

Psychiatric Medications

Antipsychotics

• Thioridazine causes 25-30 ms QT prolongation and represents one of the highest-risk antipsychotics 1, 2
• Haloperidol (especially IV route) causes 7 ms prolongation with dramatically higher torsades risk via IV compared to oral or IM administration 1, 2
• Chlorpromazine, pimozide, sertindole, and quetiapine all prolong QT interval, with quetiapine causing approximately 6 ms prolongation 1, 4, 5

Antidepressants

• Tricyclic antidepressants (amitriptyline) cause more QT prolongation than SSRIs, with mean increase of 24 ms versus -1 ms with SSRI monotherapy, particularly dangerous in overdose 1, 2
• Citalopram and escitalopram have FDA/EMA dose restrictions due to QT effects, with maximum doses reduced for patients >60 years 1, 4
• SSRIs generally have lower risk than tricyclics but still require monitoring in high-risk patients 1, 4

Mood Stabilizers and Addiction Treatment

• Methadone causes pronounced QT prolongation and requires pretreatment ECG, follow-up within 30 days, annual monitoring, and additional evaluation if daily dose exceeds 100-120 mg 1, 2
• Lithium has divergent reports but bradycardia, T wave changes, and AV-block have been documented 1

Antimicrobial Agents

Antibiotics

• Macrolides: Erythromycin (especially IV) carries highest risk among macrolides, clarithromycin and azithromycin also prolong QT with dose-dependent effects and FDA warnings about torsades de pointes 1, 2, 6
• Fluoroquinolones: Moxifloxacin causes most common QTc prolongation, followed by levofloxacin and ciprofloxacin, with increased risk in hypokalemia and elderly patients 1, 2, 7

Antifungals

• Azole antifungals (ketoconazole, voriconazole, itraconazole, fluconazole) prolong QT and should not be coadministered with bedaquiline for more than 14 days due to CYP3A4 inhibition increasing drug levels 1, 2

Antimalarials

• Chloroquine, hydroxychloroquine, halofantrine, mefloquine, and quinine all cause QT prolongation 1, 2

Other Antimicrobials

• Pentamidine significantly prolongs QT interval 1, 2

Gastrointestinal Medications

• Domperidone prolongs QTc and should be avoided entirely in at-risk patients, particularly when combined with other QT-prolonging drugs like chlorpromazine 1, 2, 4
• Metoclopramide prolongs QT but has lower risk than high-risk medications like antiarrhythmics or methadone 1, 2, 4
• 5-HT3 antagonists (ondansetron, granisetron, dolasetron) carry FDA warnings for QT prolongation 1, 2
• Cisapride (withdrawn from US market) causes QT prolongation 2

Other Medications

• Bedaquiline (anti-TB drug) requires ECG at baseline, 2 weeks, then monthly, and after addition of any QT-prolonging medication 1
• Clofazimine prolongs QT interval 1

Critical Risk Factors for Torsades de Pointes

Multiple risk factors are often present simultaneously and create additive risk that must be identified before initiating QT-prolonging therapy. 1, 2

• Female gender (consistently identified across all guidelines) 1, 2
• Advanced age (>65 years, with elderly more susceptible to drug effects on QT) 1, 2, 7
• Baseline QTc >500 ms or increase >60 ms from baseline 2
• Hypokalemia (potassium <4.5 mEq/L) or hypomagnesemia 1, 2
• Bradycardia or bradyarrhythmias 1, 2
• Congestive heart failure, structural heart disease, or left ventricular hypertrophy 1, 2
• Congenital long QT syndrome or family history of sudden cardiac death 1, 2, 6
• Recent conversion from atrial fibrillation 2
• Concomitant use of multiple QT-prolonging drugs 1, 2
• Drug interactions via CYP3A4 inhibition (azole antifungals, macrolides, protease inhibitors increase levels of QT-prolonging drugs) 1, 2
• Genetic polymorphisms affecting drug metabolism 1

Monitoring Requirements

Baseline ECG is mandatory before initiating any QT-prolonging medication, with follow-up timing based on medication risk profile. 2, 4

• Baseline ECG to measure QTc interval in all patients 2, 4
• Follow-up ECG within 7-30 days after starting therapy and after any dose change, with high-risk medications (methadone, bedaquiline) requiring more frequent monitoring 1, 2, 4
• Electrolyte monitoring (potassium, magnesium, calcium) before and periodically during treatment, maintaining potassium >4.5 mEq/L 1, 2, 4
• QTc >500 ms or increase >60 ms from baseline requires immediate medication adjustment or discontinuation 2, 4
• Document QTc in medical record using rhythm strip examples, at least every 8 hours in high-risk situations 4

Management of Drug-Induced Torsades de Pointes

Immediate removal of the offending agent and intravenous magnesium represent first-line management regardless of serum magnesium level. 1, 4

• Discontinue all QT-prolonging medications immediately 1, 4
• Intravenous magnesium sulfate 1-2 g (can suppress torsades even with normal serum magnesium through membrane-stabilizing properties, with minimal toxicity risk at these doses) 1, 4
• Potassium repletion to 4.5-5 mEq/L shortens QT interval 1
• Temporary pacing or isoproterenol for recurrent torsades de pointes to increase heart rate and shorten QT 1, 4
• Non-synchronized defibrillation for hemodynamically unstable patients 4
• Correct all electrolyte abnormalities immediately 1, 4

Common Pitfalls and Caveats

• IV administration carries dramatically higher risk than oral dosing due to greater cardiac drug exposure and rapid infusion rates, particularly evident with haloperidol where IV route increases torsades risk exponentially compared to oral or IM 2
• Not all QT prolongation leads to torsades de pointes—risk varies substantially by medication, with amiodarone causing significant prolongation but lower arrhythmia risk 2, 3
• Many non-cardiac medications cause QT prolongation, requiring vigilance across all prescribing specialties 2, 8
• Drug interactions via CYP3A4 inhibition can dramatically increase levels of QT-prolonging drugs; combination of ketoconazole with amiodarone is contraindicated 1, 2
• Combining multiple QT-prolonging drugs creates additive risk and should be avoided whenever possible 2, 4
• QT prolongation risk is dose-dependent for most medications 1
• Genetic factors may expose subclinical congenital LQTS when QT-prolonging drugs are administered 1

Safe Alternatives

Acetaminophen does not prolong the QT interval and represents a safe analgesic choice for patients with baseline QT prolongation or risk factors for torsades de pointes. 3

• Buprenorphine causes far less QT prolongation compared to methadone, though it is a partial agonist and less effective in patients requiring high doses 1