What is the management of QTc (corrected QT) interval prolongation due to arsenic exposure?

From the Guidelines

Management of QTc Interval Prolongation due to Arsenic Exposure Arsenic exposure can lead to QTc interval prolongation, increasing the risk of torsades de pointes, and therefore, it is crucial to monitor the QTc interval closely in patients receiving arsenic therapy 1.

Monitoring and Maintenance

To manage QTc interval prolongation, the following steps can be taken:

• Monitor electrocardiograms (ECGs) at baseline, after 1-2 weeks of arsenic therapy, and then periodically, with weekly monitoring recommended for patients receiving treatment with arsenic trioxide 1.
• Maintain potassium levels above 4.0 mEq/L and magnesium levels above 1.8 mg/dL to reduce the risk of QTc interval prolongation 1.
• Consider using potassium and magnesium supplements if necessary, with a typical dose of potassium gluconate 20 mEq orally twice daily and magnesium oxide 400 mg orally twice daily.

Avoiding Concomitant Medications

• Avoid concomitant use of other medications that can prolong the QTc interval, such as quinolones, macrolides, and antipsychotics 1.
• Check crediblemeds.org for a full list of QT-prolonging drugs and which concomitant drugs should be avoided whenever possible 1.

Dose Adjustment and Discontinuation

• If the QTc interval exceeds 500 ms, consider reducing the arsenic dose or discontinuing therapy 1.
• In cases where the QTc interval exceeds 520 ms, arsenic therapy should be discontinued.
• If no alternative therapy exists, the frequency of ECG monitoring of the QT interval should be increased, and the benefits of arsenic therapy should be weighed against the risks of QTc interval prolongation 1.

Emergency Management

• In cases of torsade de pointes, intravenous administration of magnesium sulphate (10 mL) and, in some acute situations, overdrive transvenous pacing or isoprenaline titrated to a heart rate >90 beats per minute may be necessary to prevent new episodes in the acute setting 1.
• If sustained ventricular arrhythmias and haemodynamic instability occur, non-synchronized defibrillation must be performed 1.

From the Research

Management of QTc Interval Prolongation due to Arsenic Exposure

The management of QTc interval prolongation due to arsenic exposure involves several key considerations:

• Monitoring of electrocardiography (EKG) and electrolytes is necessary to prevent torsades de pointes (TdP) 2, 3, 4, 5, 6
• Risk factors for TdP include hypokalemia, female sex, drug-drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation 4, 6
• 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 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 4
• 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 4

Prevention and Management Strategies

Prevention and management strategies for QTc interval prolongation due to arsenic exposure include:

• Avoiding the use of arsenic trioxide in patients with pre-existing QTc interval prolongation or other risk factors for TdP 2
• Monitoring patients for signs and symptoms of TdP, such as palpitations, lightheadedness, dizziness or syncope 4
• Correcting electrolyte abnormalities, such as hypokalemia and hypomagnesemia, to reduce the risk of TdP 4, 6
• Discontinuing the offending drug and administering intravenous magnesium sulfate 1 to 2 g in cases of hemodynamically stable TdP 6

Role of Healthcare Professionals

Healthcare professionals, including pharmacists, play an important role in minimizing the risk of drug-induced QTc interval prolongation and TdP through:

• Knowledge of drugs that are associated with a known or possible risk of TdP 6
• Individualized assessment of risk of drug-induced QTc interval prolongation 6
• Awareness of drug interactions most likely to result in TdP 6
• Attention to dose reduction of renally eliminated QTc interval-prolonging drugs in patients with kidney disease 6