What action to take with prolonged QTc interval in a female patient on quetiapine (quetiapine fumarate)?

From the Guidelines

For a female patient with a QTc interval of 460 ms who is taking quetiapine, close monitoring is recommended but immediate discontinuation is not typically necessary. This QTc value is only mildly prolonged for females (normal is <460 ms, with borderline being 460-479 ms) 1. The patient's current quetiapine dose can be continued, but a follow-up ECG should be obtained within 1-2 weeks to ensure stability. Other QT-prolonging medications in her regimen should be identified and considered for discontinuation or replacement if possible. Electrolyte abnormalities, particularly potassium, magnesium, and calcium levels, should be evaluated and corrected. The patient should be monitored for symptoms such as dizziness, palpitations, or syncope, which could indicate worsening cardiac effects. If the QTc increases to >500 ms or increases by >60 ms from baseline, consideration should be given to dose reduction or switching to an antipsychotic with lower QT prolongation risk, such as aripiprazole or lurasidone. Quetiapine has a moderate risk of QT prolongation, and the risk increases with higher doses, electrolyte abnormalities, heart disease, and concomitant QT-prolonging medications 1. The concern with QT prolongation is the increased risk of torsades de pointes, a potentially fatal arrhythmia, and risk factors for drug-induced torsades de pointes include female gender, hypokalemia, bradycardia, and congenital long QT syndrome 1. Key considerations in managing this patient include:

• Monitoring for QT prolongation and associated risks
• Managing electrolyte abnormalities and other risk factors
• Considering alternative antipsychotic medications with lower QT prolongation risk if necessary.

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. 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) Caution should also be exercised when quetiapine is prescribed in patients with increased risk of QT prolongation (e.g., cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure, and heart hypertrophy).

For a female patient on quetiapine with a QTc of 460, it is essential to exercise caution due to the increased risk of QT prolongation. The patient should be monitored closely for any signs of torsade de pointes or sudden death.

• Key considerations:
  • Cardiovascular disease: presence of any cardiovascular conditions that may increase the risk of QT prolongation
  • Family history of QT prolongation: any family history that may predispose the patient to QT prolongation
  • Concomitant medications: avoid using quetiapine with other medications known to prolong the QTc interval
  • Electrolyte imbalance: monitor and manage any electrolyte imbalances, particularly hypokalemia or hypomagnesemia, which can increase the risk of QT prolongation Given the patient's QTc interval of 460, which is considered prolonged, and the fact that quetiapine may contribute to QT prolongation, a conservative clinical decision would be to:
• Monitor the patient closely for any signs of torsade de pointes or sudden death
• Consider alternative treatments that do not carry the same risk of QT prolongation
• Manage any concomitant conditions or medications that may increase the risk of QT prolongation 2

From the Research

QTc Prolongation and Quetiapine

• A QTc interval of 460 ms in a female patient is considered prolonged, as normal QTc intervals are typically <450 ms for men and <460 ms for women 3.
• Quetiapine is associated with QT prolongation, and the risk of arrhythmic events increases with the degree of QT prolongation 4, 5.

Risk Factors for QTc Prolongation

• Female sex is a risk factor for QTc prolongation, and the patient's sex should be taken into account when assessing the risk of QTc prolongation 4, 3.
• Other risk factors for QTc prolongation include older age, pre-existing cardiovascular disease, electrolyte abnormalities, and non-psychiatric medications 4, 3.

Management of QTc Prolongation

• For patients with a QTc interval >500 ms, a change in pharmacologic treatment can be considered, though a particular medication may still be warranted if the risks of discontinuation outweigh the risks of arrhythmias 4.
• For patients with a QTc interval <500 ms, the use of antipsychotics such as aripiprazole, olanzapine, risperidone, or quetiapine can be considered, with close monitoring of the QTc interval 6.
• Regular ECG monitoring is recommended, using a linear regression formula to correct for heart rate 4.

Alternative Treatment Options

• Aripiprazole is associated with a lower risk of QTc prolongation and may be a suitable alternative for patients at risk of QTc prolongation 5, 7, 6.
• Other antipsychotics, such as olanzapine and risperidone, may also be considered, but with close monitoring of the QTc interval 6.