What medications can increase the QT interval in inpatients?

Common Inpatient Medications That Prolong QT Interval

High-Risk Antipsychotics

The antipsychotics with the highest risk of QT prolongation in hospitalized patients are thioridazine (25-30 ms prolongation), intravenous haloperidol (7 ms prolongation, higher risk than oral/IM routes), and pimozide (13 ms prolongation). 1, 2, 3

• Thioridazine carries an FDA black box warning and causes 25-30 ms mean QTc prolongation, making it the highest-risk antipsychotic 2, 3
• Intravenous haloperidol has significantly higher arrhythmia risk compared to oral or intramuscular administration, with 7 ms mean prolongation 1, 3
• Chlorpromazine increases risk of QTc prolongation with adjusted relative risk of 1.37 per 100 mg dose 4
• Ziprasidone causes 5-22 ms prolongation 2, 3
• Quetiapine causes approximately 6 ms prolongation 5, 6

Moderate-Risk Antipsychotics

• Clozapine causes 8-10 ms mean QTc prolongation 3
• Olanzapine causes minimal (2 ms) prolongation 3
• Risperidone causes 0-5 ms prolongation 3

Lowest-Risk Antipsychotics

Aripiprazole has 0 ms mean QTc prolongation and should be the preferred antipsychotic when QT concerns exist. 5, 3

Antiarrhythmic Medications

Class IA antiarrhythmics (quinidine, procainamide, disopyramide) and Class III antiarrhythmics (sotalol, dofetilide, ibutilide) are among the highest-risk medications for QT prolongation. 2, 6

• Sotalol is contraindicated if baseline QT >450 msec and requires hospitalization for initiation with continuous ECG monitoring 7
• Amiodarone markedly prolongs QT but rarely causes torsades de pointes due to uniform repolarization delay across all myocardial layers 1, 2

Antibiotics

Macrolides (clarithromycin, erythromycin, azithromycin) and fluoroquinolones (moxifloxacin, levofloxacin, ciprofloxacin) commonly prolong QT in hospitalized patients. 2, 8

• Azithromycin causes dose-dependent QTc prolongation: 5 ms at 500 mg, 7 ms at 1000 mg, and 9 ms at 1500 mg daily 8
• Moxifloxacin and levofloxacin carry significant risk 2
• Pentamidine (used for Pneumocystis pneumonia) prolongs QT 2, 6

Antiemetics

Ondansetron, dolasetron, domperidone, droperidol, and metoclopramide all prolong QT interval. 5, 2

• Domperidone combined with other QT-prolonging drugs (like chlorpromazine) presents significant arrhythmia risk and should be avoided 5
• Metoclopramide has lower risk than high-risk medications but requires monitoring, especially with concomitant QT-prolonging drugs 5

Antidepressants

Tricyclic antidepressants (amitriptyline) cause more QT prolongation than SSRIs, particularly in overdose situations. 1, 9

• Citalopram and escitalopram can prolong QT 1, 5
• Sertraline has lower risk than tricyclics but can still prolong QT 5
• Venlafaxine and mirtazapine are listed as QT-prolonging antidepressants 5
• Combining antidepressants with antipsychotics significantly increases QT prolongation risk (mean increase 24 ms vs -1 ms with monotherapy) 10

Opioids and Pain Medications

Methadone is a high-risk medication for QT prolongation, with nearly 1 million Americans using it for narcotic dependence or chronic pain. 1, 5, 2

• Guidelines recommend pretreatment ECG, follow-up ECG within 30 days, and annual monitoring for methadone patients 1

Antifungals

• Ketoconazole and other imidazole antimycotics prolong QT 2

Antimalarials

• Chloroquine and hydroxychloroquine cause QT prolongation 2

Critical Risk Factors That Amplify Medication Effects

Female sex, age >65 years, baseline QTc >500 ms, hypokalemia, hypomagnesemia, bradycardia, and concomitant use of multiple QT-prolonging drugs are the most important risk factors. 1, 5, 2, 3

• Electrolyte abnormalities (particularly potassium <4.5 mEq/L and low magnesium) must be corrected before initiating QT-prolonging medications 1, 5
• Pre-existing cardiovascular disease, heart failure, and left ventricular hypertrophy increase risk 1, 2, 6
• Recent conversion from atrial fibrillation increases torsades risk 2

Monitoring Algorithm

Obtain baseline ECG before starting any QT-prolonging medication, repeat ECG within 7 days after initiation or dose change, and discontinue if QTc exceeds 500 ms or increases >60 ms from baseline. 5, 2, 3

• Measure QTc 2-4 hours after each dose during high-risk situations 5, 7
• Monitor electrolytes (potassium, magnesium, calcium) before and during treatment 5, 3
• Document QTc in medical record using rhythm strip examples at least every 8 hours in high-risk patients 5

Common Pitfall

Intravenous administration carries higher risk than oral dosing due to greater cardiac drug exposure and rapid infusion rates. 1 This is particularly important for haloperidol, where IV route dramatically increases torsades risk compared to oral or IM administration 1, 3, 9.