Summary

Quinidine and dofetilide have a contraindicated interaction that significantly increases the risk of life-threatening cardiac arrhythmias. This combination should be avoided due to additive effects on cardiac repolarization and potential for fatal outcomes.

Introduction

Quinidine is a Class IA antiarrhythmic medication primarily used to treat atrial fibrillation, atrial flutter, and ventricular arrhythmias. It works by blocking sodium channels and has additional effects on potassium channels. Dofetilide is a Class III antiarrhythmic agent specifically indicated for the conversion and maintenance of normal sinus rhythm in patients with atrial fibrillation or atrial flutter. It selectively blocks potassium channels, particularly the rapid component of the delayed rectifier potassium current (IKr).

Mechanism of Interaction

The interaction between quinidine and dofetilide occurs through additive effects on cardiac repolarization. Both drugs prolong the QT interval by blocking potassium channels, though through different mechanisms. Quinidine blocks multiple ion channels including IKr, while dofetilide selectively blocks IKr channels. When used together, these effects are additive, leading to excessive QT prolongation and increased risk of torsades de pointes, a potentially fatal ventricular arrhythmia. Additionally, quinidine may inhibit the renal elimination of dofetilide, further increasing dofetilide plasma concentrations.

Risks and Symptoms

The concurrent use of quinidine and dofetilide poses severe clinical risks including marked QT interval prolongation, increased risk of torsades de pointes (a polymorphic ventricular tachycardia), and potential sudden cardiac death. This interaction is classified as contraindicated due to the high probability of serious adverse outcomes. Patients may experience palpitations, syncope, seizures, or cardiac arrest. The risk is particularly elevated in patients with underlying heart disease, electrolyte imbalances, or renal impairment.

Management and Precautions

Quinidine and dofetilide should never be used concurrently. If a patient is currently taking one of these medications and requires treatment with the other, the first drug must be discontinued with appropriate washout period before initiating the second agent. For quinidine, allow at least 2-3 elimination half-lives (approximately 12-18 hours) before starting dofetilide. When discontinuing dofetilide, wait at least 2 days before initiating quinidine. Alternative antiarrhythmic agents should be considered. If either drug is accidentally co-administered, immediate cardiac monitoring, electrolyte correction, and emergency medical intervention may be required.

Quinidine interactions with food and lifestyle

Quinidine has several important food and lifestyle interactions that patients should be aware of. Grapefruit juice should be avoided as it can significantly increase quinidine blood levels by inhibiting CYP3A4 metabolism, potentially leading to dangerous side effects including cardiac arrhythmias. Alcohol consumption should be limited or avoided as it may enhance quinidine's cardiac depressant effects and increase the risk of arrhythmias. High-sodium foods and salt substitutes containing potassium should be used cautiously, as electrolyte imbalances can affect quinidine's effectiveness and increase toxicity risk. Patients should maintain consistent dietary habits and avoid large changes in alkaline foods (such as citrus fruits, dairy products, and vegetables) as these can affect urine pH and alter quinidine elimination from the body. Smoking cessation is recommended as tobacco use can affect quinidine metabolism. Patients should also avoid excessive caffeine intake as it may increase the risk of cardiac side effects when combined with quinidine.

Dofetilide interactions with food and lifestyle

Dofetilide should be taken consistently with regard to meals - either always with food or always without food. Grapefruit juice should be avoided as it may increase dofetilide blood levels and risk of dangerous heart rhythm abnormalities. Alcohol should be used with caution as it may worsen heart rhythm problems. Patients should maintain consistent potassium and magnesium levels through diet, as low levels of these electrolytes can increase the risk of serious arrhythmias with dofetilide.