What medications increase the QT(c) (corrected QT) interval?

From the Guidelines

Medications that can increase the QTc interval include antipsychotics like haloperidol, thioridazine, and ziprasidone, as well as antibiotics such as macrolides, fluoroquinolones, and antifungals, which can potentially lead to dangerous heart rhythm disturbances. According to the most recent study 1, other notable medications that can extend the QTc interval include antiarrhythmic drugs, particularly Class IA and Class III medications, certain antidepressants, antiemetics, and methadone. The risk of QTc interval prolongation increases with higher doses and when combining multiple QTc-prolonging drugs, which can affect cardiac repolarization by blocking potassium channels in heart cells, delaying ventricular repolarization and extending the QTc interval.

Key Medications that Prolong QTc Interval

• Antipsychotics: haloperidol, thioridazine, ziprasidone
• Antibiotics: macrolides (erythromycin, azithromycin, clarithromycin), fluoroquinolones (moxifloxacin, levofloxacin), antifungals (fluconazole, ketoconazole)
• Antiarrhythmic drugs: Class IA (quinidine, procainamide), Class III (amiodarone, sotalol, dofetilide)
• Antidepressants: citalopram, escitalopram
• Antiemetics: ondansetron, domperidone
• Opioids: methadone

Risk Factors for QTc Interval Prolongation

• Pre-existing heart conditions
• Electrolyte abnormalities (especially low potassium or magnesium)
• Genetic predispositions
• Higher doses of QTc-prolonging medications
• Combining multiple QTc-prolonging drugs

Monitoring and Management

Monitoring the QTc interval before and during treatment with these medications is crucial, particularly in high-risk patients, as recommended by 1. If the QTc interval reaches a length >500 ms or increases by >60 ms compared with baseline, treatment with the particular drug should be ceased or dose reduced. Additionally, hypokalemia should be avoided, and concomitant treatment with more than one drug with the propensity of prolonging the QT interval should be avoided if possible.

From the FDA Drug Label

In clinical trials, quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. In post marketing experience, there were cases reported of QT prolongation in patients who overdosed on quetiapine [see OVERDOSAGE (10. 1)] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS (7.1)] . Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Cases of torsades de pointes have been spontaneously reported during postmarketing surveillance in patients receiving clarithromycin.

The following medications may increase the QTc interval:

• Quetiapine 2: may increase QTc interval, especially in patients with concomitant illness or taking medicines known to cause electrolyte imbalance or increase QT interval.
• Clarithromycin 3: has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Medications to avoid with quetiapine or clarithromycin due to increased risk of QT prolongation:
• Class 1A antiarrhythmics (e.g., quinidine, procainamide)
• Class III antiarrhythmics (e.g., amiodarone, sotalol)
• Antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine)
• Antibiotics (e.g., gatifloxacin, moxifloxacin)
• Other medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

From the Research

Medications that Increase QTc Interval

The following medications have been associated with an increased QTc interval:

• Antipsychotics:
  • Thioridazine 4, 5, 6, 7, 8
  • Haloperidol 4, 5, 6, 7, 8
  • Ziprasidone 4, 5, 6, 7, 8
  • Quetiapine 5, 7, 8
  • Risperidone 5, 6, 7, 8
  • Olanzapine 5, 6, 7, 8
  • Sertindole 7
  • Pimozide 5, 7
  • Amisulpride 5
  • Clozapine 5, 8
  • Flupenthixol 5
  • Fluphenazine 5
  • Melperone 5
  • Perphenazine 5
  • Sulpiride 5
• Antidepressants:
  • Citalopram 4
  • Selective serotonin reuptake inhibitors (SSRIs) 4, 7
  • Tricyclic antidepressants (TCAs) 7
  • Amitriptyline 7
  • Imipramine 7
  • Doxepin 7
  • Trazadone 7, 8
  • Fluoxetine 7

Risk Factors for QTc Prolongation

The following risk factors can contribute to QTc prolongation:

• Female gender 5, 7
• Age over 65 years 7
• Congestive heart failure 5
• Hypokalemia 5, 6, 7
• Hypomagnesemia 5, 6
• Bradycardia 5, 6, 7
• Concomitant use of other medications that affect the QT interval 5, 6, 7
• Genetic predisposition 6, 7
• Substance abuse 7
• Anorexia nervosa 7
• Congenital Long QT syndrome 7