What precautions should be taken when prescribing medications that prolong the QTc (QT interval corrected) interval?

From the Guidelines

When prescribing medications that prolong the QTc interval, clinicians should first assess the patient's baseline risk factors for QT prolongation and obtain a baseline ECG to measure the QTc interval, as recommended by the most recent guidelines 1. Before initiating therapy, it is essential to check electrolytes, particularly potassium, magnesium, and calcium, correcting any abnormalities.

• Avoid prescribing multiple QT-prolonging medications simultaneously when possible.
• Common QT-prolonging medications include certain antipsychotics (haloperidol, ziprasidone), antiarrhythmics (amiodarone, sotalol), antibiotics (azithromycin, moxifloxacin), and antidepressants (citalopram, escitalopram).
• Start with the lowest effective dose and titrate cautiously.
• For high-risk patients, perform follow-up ECGs after reaching steady-state concentrations or after dose increases.
• Monitor and maintain electrolytes within normal ranges throughout treatment.
• Educate patients about warning symptoms such as palpitations, dizziness, or syncope that may indicate arrhythmias.
• Consider alternative medications in patients with congenital long QT syndrome, history of torsades de pointes, heart failure, bradycardia, or those taking other QT-prolonging drugs, as suggested by 1 and 1. These precautions are crucial because QT prolongation increases the risk of developing torsades de pointes, a potentially fatal ventricular arrhythmia that can lead to sudden cardiac death, highlighting the importance of careful management and monitoring 1.

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)]. The use of quetiapine should be avoided in combination with other drugs that are known to prolong QTc including Class 1A antiarrythmics (e.g., quinidine, procainamide) or Class III antiarrythmics (e.g., amiodarone, sotalol), antipsychotic medications (e.g., ziprasidone, chlorpromazine, thioridazine), antibiotics (e.g., gatifloxacin, moxifloxacin), or any other class of medications known to prolong the QTc interval (e.g., pentamidine, levomethadyl acetate, methadone)

Precautions for QTc prolonging medications:

• Avoid combining quetiapine with other drugs that prolong QTc.
• Avoid using quetiapine in patients with a history of cardiac arrhythmias, hypokalemia, or hypomagnesemia.
• Use caution when prescribing quetiapine to patients with increased risk of QT prolongation, such as those with cardiovascular disease, family history of QT prolongation, or congestive heart failure.
• Monitor patients for signs of QT prolongation, such as torsade de pointes or sudden death. 2

From the Research

Precautions for Prescribing QTc Prolonging Medications

When prescribing medications that prolong the QTc interval, several precautions should be taken to minimize the risk of torsades de pointes (TdP) and other serious cardiac arrhythmias.

• Assessment of Risk Factors: Patients with baseline clinical risk factors for QTc prolongation, such as hypokalemia, hypomagnesemia, and heart failure, should be closely monitored 3.
• Selection of Medications: The choice of medication should be based on the patient's individual risk factors and the potential for QTc prolongation. For example, citalopram and thioridazine are more likely to induce QTc prolongation than other antidepressants and antipsychotics 4.
• Dose Adjustment: The dose of the medication should be adjusted based on the patient's renal function and other factors that may affect the drug's pharmacokinetics 5.
• Cardiac Monitoring: The frequency of cardiac monitoring should be individually determined based on the prescribed agent and additional risk factors for TdP 4.
• Electrolyte Monitoring: Electrolyte levels, such as potassium and magnesium, should be closely monitored to prevent hypokalemia and hypomagnesemia, which can increase the risk of QTc prolongation 5, 3.
• Avoidance of Drug Interactions: Pharmacists should be aware of potential drug interactions that can increase the risk of QTc prolongation, such as the use of antifungal agents, macrolide antibiotics, and drugs to treat human immunodeficiency virus with amiodarone, disopyramide, dofetilide, or pimozide 5.

High-Risk Patients

Certain patient populations are at higher risk for QTc prolongation and TdP, including:

• Elderly Patients: Advanced age is a risk factor for QTc prolongation and TdP 5, 3.
• Female Patients: Female sex is a risk factor for QTc prolongation and TdP 5, 3.
• Patients with Cardiovascular Disease: Patients with heart failure, acute myocardial infarction, and other cardiovascular diseases are at higher risk for QTc prolongation and TdP 5, 3.
• Critically Ill Patients: ICU patients are particularly prone to experience QTc interval prolongation due to exposure to certain drugs and prevalent risk factors for TdP 6.

Management of QTc Prolongation

If QTc prolongation occurs, the following steps should be taken:

• Discontinuation of the Offending Drug: The medication causing the QTc prolongation should be discontinued 5, 6.
• Correction of Electrolyte Abnormalities: Electrolyte levels, such as potassium and magnesium, should be corrected to prevent further QTc prolongation 5, 6.
• Administration of Intravenous Magnesium Sulfate: Intravenous magnesium sulfate may be administered to help manage QTc prolongation and prevent TdP 5, 6.