How to manage QTc prolongation in a patient taking Abilify (aripiprazole) and Klonopin (clonazepam)?

From the Guidelines

To manage QTc prolongation in a patient taking Abilify (aripiprazole) and Klonopin (clonazepam), it is crucial to obtain a baseline ECG and monitor electrolyte levels, considering treatment discontinuation or alternative regimens if the QTc is ≥500 ms, as recommended by the European Society of Cardiology 1. When managing QTc prolongation in patients on these medications, several key points must be considered:

• A 12-lead ECG should be recorded at baseline to assess the QT interval, corrected for heart rate with Bazett’s or Fridericia’s formula, as suggested by the European Society of Cardiology 1.
• Patients with a history of QT prolongation, relevant cardiac disease, or those treated with QT-prolonging drugs like aripiprazole should be monitored by repeated 12-lead ECG, especially if they have bradycardia, thyroid dysfunction, or electrolyte abnormalities 1.
• Ensuring potassium, magnesium, and calcium levels are within normal ranges is vital, as electrolyte abnormalities can exacerbate QTc prolongation.
• While clonazepam itself does not significantly affect the QTc interval, its additive effects when combined with other medications should be considered, and the use of other QTc-prolonging medications should be minimized.
• For patients with moderate QTc prolongation (QTc 470-500ms), more frequent ECG monitoring (every 1-3 months) is recommended, and if QTc exceeds 500ms, consultation with cardiology and consideration of switching aripiprazole to a medication with a lower QTc risk, such as lurasidone or brexpiprazole, is necessary due to the increased risk of Torsades de Pointes 1. Key considerations include:
• Avoiding conditions known to provoke torsades de pointes, especially hypokalemia and extreme bradycardia, in patients with drug-induced QT prolongation 1.
• Regular review and addressing of modifiable risk factors like hypokalemia, hypomagnesemia, or concomitant use of other QTc-prolonging medications.

From the FDA Drug Label

In the event of an overdose of aripiprazole, an electrocardiogram should be obtained and if QT interval prolongation is present, cardiac monitoring should be instituted Management of overdose should concentrate on supportive therapy, maintaining an adequate airway, oxygenation and ventilation, and management of symptoms

QTc Prolongation Management: In a patient taking Abilify (aripiprazole) and Klonopin (clonazepam) with QTc prolongation,

• An electrocardiogram should be obtained to confirm the presence of QT interval prolongation
• If QT interval prolongation is present, cardiac monitoring should be instituted
• Management should concentrate on supportive therapy, maintaining an adequate airway, oxygenation, and ventilation, and management of symptoms 2

From the Research

Management of QTc Prolongation

• QTc prolongation is a significant concern in patients taking Abilify (aripiprazole) and Klonopin (clonazepam), as it can increase the risk of torsades de pointes (TdP) 3, 4.
• Risk factors for QTc prolongation include hypokalemia, female sex, drug-drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation 3.
• Patients at risk for QT interval prolongation should be educated to go directly to the emergency room if they experience palpitations, lightheadedness, dizziness, or syncope 3.

Monitoring and Management

• Close monitoring for QTc prolongation is necessary to prevent TdP, and a baseline ECG may not be necessary for individuals at low risk for arrhythmia 4.
• When the QTc interval is 470-500 ms for males, or 480-500 ms for females, or the QTc interval increases 60 ms or more from pretreatment values, dose reduction or discontinuation of the offending drug should be considered where possible, and electrolytes corrected as needed 3.
• If the QTc interval is ≥500 ms, the offending drug should be discontinued, and continuous EKG telemetry monitoring should be performed, or the 12-lead EKG should be repeated every 2-4 hours, until the QT interval has normalized 3.

Specific Considerations for Abilify and Klonopin

• Aripiprazole (Abilify) is generally considered to have a low risk of QTc prolongation 5, 6.
• Clonazepam (Klonopin) is a benzodiazepine and is not typically associated with QTc prolongation, but it can exacerbate underlying cardiac conditions 7.
• The combination of Abilify and Klonopin may still pose a risk for QTc prolongation, and careful monitoring is necessary 3, 4.