What medications prolong the QTc (corrected QT) interval?

Medications That Prolong QTc Interval

Multiple medication classes can prolong the QTc interval, increasing the risk of potentially fatal ventricular arrhythmias like torsades de pointes, with antipsychotics, certain antibiotics, cardiac medications, and antiemetics being among the highest risk agents. 1, 2

Common QT-Prolonging Medications by Class

Antipsychotics

• High risk: Thioridazine (25-30ms prolongation), ziprasidone (5-22ms), pimozide (13ms) 1
• Moderate risk: Clozapine (8-10ms), haloperidol (7ms), quetiapine (6ms) 1
• Lower risk: Risperidone (0-5ms), olanzapine (2ms), aripiprazole (0ms) 1, 3

Antibiotics

• Macrolides: Azithromycin, clarithromycin, erythromycin 1
• Fluoroquinolones: Ciprofloxacin, levofloxacin, moxifloxacin 1, 4
• Others: Trimethoprim-sulfamethoxazole, pentamidine 1

Cardiac Medications

• Antiarrhythmics: Quinidine, procainamide, amiodarone, sotalol, disopyramide 1, 5
• Others: Adenosine, dopamine, epinephrine, dobutamine 1

Antiemetics

• Ondansetron, dolasetron 1, 2

Antimalarials

• Quinine, chloroquine, halofantrine 1

Antidepressants

• Tricyclic antidepressants (e.g., amitriptyline, desipramine, nortriptyline) 1

Other Medications

• Antihistamines: Diphenhydramine, hydroxyzine, loratadine 1
• Respiratory: Albuterol, terbutaline, phenylephrine 1
• Antiviral: Amantadine 1
• Antifungal: Ketoconazole and other imidazole antimycotics 1

Risk Stratification and Monitoring

QTc Risk Categories

• High risk: QTc >500ms
• Intermediate risk: QTc 450-499ms (males) or 470-499ms (females)
• Low risk: QTc <450ms (males) or <470ms (females) 2

Patient-Specific Risk Factors

• Female gender
• Advanced age
• Cardiac disease
• Bradycardia
• Electrolyte disturbances (especially hypokalemia and hypomagnesemia)
• Concomitant use of multiple QT-prolonging medications 2, 6

Monitoring Recommendations

1. Obtain baseline ECG before starting medications that prolong QT interval
2. Repeat ECG when stable medication levels are reached
3. Monitor with dose adjustments
4. Repeat ECG when starting other QT-prolonging medications
5. Monitor for electrolyte disturbances 2

Management of QTc Prolongation

When to Consider Medication Changes

• QTc increases to >500ms
• QTc increases by >60ms from baseline
• Patient develops symptoms of arrhythmia
• Multiple risk factors for QT prolongation are present 2

Risk Reduction Strategies

1. Maintain potassium >4.0 mEq/L and magnesium >2.0 mg/dL
2. Correct electrolyte abnormalities before using QT-prolonging medications
3. Avoid combinations of QT-prolonging medications when possible
4. Consider alternative medications with lower QT risk when appropriate 2, 6

Special Considerations

Antipsychotics

The most feared cardiac adverse effect of antipsychotics is quinidine-like QTc prolongation, resulting in dysrhythmias such as torsades de pointes. QTc prolongation occurs with therapeutic dosing and is possible with any antipsychotic medication, though risk varies significantly between agents 1, 7.

Antibiotics

Fluoroquinolones and macrolides can cause QT prolongation with varying degrees of risk. The risk of malignant arrhythmia is approximately one per million for ciprofloxacin, 3 per million for clarithromycin, and 14.5 per million for sparfloxacin 1.

Drug Interactions

Many medications can interact to increase QT prolongation risk. For example, ketoconazole and other imidazole antifungals inhibit cytochrome P450, potentially increasing levels of QT-prolonging drugs metabolized by this pathway 1, 5.

Clinical Pitfalls to Avoid

1. Ignoring drug interactions: Many QT-prolonging medications interact through the cytochrome P450 system, potentially increasing QT risk 1, 5

2. Overlooking electrolyte disturbances: Hypokalemia and hypomagnesemia significantly increase the risk of QT prolongation and should be corrected before administering QT-prolonging medications 2, 6

3. Failing to recognize high-risk combinations: Using multiple QT-prolonging medications simultaneously substantially increases risk 2

4. Inadequate monitoring: Patients receiving QT-prolonging medications should have appropriate ECG monitoring, especially when starting therapy or changing doses 2

5. Disregarding patient-specific risk factors: Female gender, advanced age, cardiac disease, and bradycardia all increase risk and should be considered when prescribing 2, 8