From the Guidelines
Drug-induced QTc interval prolongation is a significant concern that can lead to potentially fatal arrhythmias like Torsades de Pointes, and management involves correcting electrolyte imbalances, discontinuing or reducing doses of offending medications, and avoiding concurrent use of multiple QTc-prolonging drugs, as recommended by the 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. When prescribing medications that can prolong the QTc interval, including antiarrhythmics, antipsychotics, antibiotics, antidepressants, and antiemetics, baseline ECG assessment is recommended, with follow-up ECGs after reaching steady-state concentrations. Risk factors for drug-induced QTc prolongation include:
- Female sex
- Advanced age
- Electrolyte abnormalities, especially hypokalemia and hypomagnesemia
- Heart disease
- Genetic predisposition Generally, a QTc interval exceeding 500 ms or an increase of more than 60 ms from baseline warrants concern, and conditions known to provoke torsades de pointes, especially hypokalaemia and extreme bradycardia, should be avoided in patients with drug-induced QT prolongation, as stated in the 2016 ESC position paper on cancer treatments and cardiovascular toxicity 1. These drugs affect cardiac repolarization by blocking potassium channels, particularly the hERG channel, which delays ventricular repolarization and extends the QTc interval, creating vulnerability to early afterdepolarizations and triggered arrhythmias. In patients with drug-induced QTc interval prolongation, removal of the offending agent is indicated, as recommended by the ACC/AHA/ESC 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death 1. It is also important to minimize exposure to other QT-prolonging drugs in patients treated with potentially QT-prolonging chemotherapy, as recommended by the 2017 ESC position paper on cancer treatments and cardiovascular toxicity 1. Overall, careful monitoring and management of drug-induced QTc interval prolongation are crucial to prevent potentially fatal arrhythmias and improve patient outcomes.
From the FDA Drug Label
5.2 QT Prolongation 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. Fatalities have been reported Avoid clarithromycin in the following patients: patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, including torsades de pointes patients receiving drugs known to prolong the QT interval patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, clinically significant bradycardia and in patients receiving Class IA (e.g., quinidine, procainamide, disopyramide) or Class III (e.g., dofetilide, amiodarone, sotalol) antiarrhythmic agents.
- QTc interval change due to drugs: Clarithromycin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia, including torsades de pointes.
- The use of clarithromycin should be avoided in patients with known prolongation of the QT interval, ventricular cardiac arrhythmia, or those receiving drugs known to prolong the QT interval.
- Elderly patients may be more susceptible to drug-associated effects on the QT interval 2.
- Quetiapine should also be avoided in combination with other drugs that are known to prolong QTc, including Class 1A antiarrhythmics or Class III antiarrhythmics, antipsychotic medications, antibiotics, or any other class of medications known to prolong the QTc interval 3.
From the Research
QTc Interval Change Due to Drugs
- The QTc interval can be prolonged due to various drugs, including antibiotics, antidepressants, and cardiovascular drugs, which can increase the risk of torsades de pointes (TdP) 4, 5, 6.
- Risk factors for TdP include QTc interval >500 ms, increase in QTc interval ≥60 ms from the pretreatment value, advanced age, female sex, acute myocardial infarction, heart failure with reduced ejection fraction, hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, and treatment with diuretics 4, 6.
- Pharmacokinetic drug interactions can also increase the risk of TdP, particularly with antifungal agents, macrolide antibiotics, and drugs to treat human immunodeficiency virus interacting with amiodarone, disopyramide, dofetilide or pimozide 4.
- Erythromycin, a macrolide antibiotic, has been linked to QTc interval prolongation and TdP, particularly in patients with severe illness, female sex, older age, presence of heart disease, and concomitant administration of other QTc prolonging drugs or agents that inhibit CYP3A4 7, 8.
- Close monitoring of electrocardiography (EKG) and electrolytes is necessary to prevent TdP, and patients at risk should be educated to seek medical attention if they experience palpitations, lightheadedness, dizziness, or syncope 6.