From the Research
Tizanidine should be used with caution in patients with prolonged QTc intervals due to potential cardiac risks, as it can cause QT interval prolongation by blocking the rapid component of the delayed rectifier potassium current (I(Kr)) 1.
Mechanism and Risk Factors
Tizanidine, a centrally-acting muscle relaxant, can cause QT interval prolongation in some patients, especially at higher doses. If a patient has a pre-existing prolonged QTc interval or is taking other medications that prolong the QTc, the risk of developing dangerous cardiac arrhythmias like torsades de pointes increases. The mechanism behind tizanidine's effect on cardiac conduction involves its action on alpha-2 adrenergic receptors, which can influence heart rate and cardiac repolarization. Other risk factors for QTc interval prolongation include hypokalemia, female sex, drug-drug interactions, advancing age, genetic predisposition, hypomagnesemia, heart failure, bradycardia, and corrected QT (QTc) interval prolongation 2, 3, 4.
Clinical Recommendations
For patients with known QTc prolongation, consider starting with a lower dose of tizanidine (such as 2mg) and monitoring closely, or choose an alternative muscle relaxant like baclofen or cyclobenzaprine if appropriate for the patient's condition. Before initiating tizanidine therapy in at-risk patients, obtain a baseline ECG and consider periodic ECG monitoring during treatment. Additionally, check for drug interactions with other QT-prolonging medications and correct any electrolyte abnormalities (particularly potassium, magnesium, and calcium) as these can exacerbate QT prolongation. 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 2, 4.
Monitoring and Management
Close monitoring for QTc prolongation is necessary to prevent torsades de pointes. 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. 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.