Summary

The combination of dofetilide and hydrochlorothiazide requires careful monitoring due to increased risk of dangerous heart rhythm abnormalities. Hydrochlorothiazide can cause electrolyte imbalances that may enhance dofetilide's proarrhythmic effects, particularly torsades de pointes.

Introduction

Dofetilide is a Class III antiarrhythmic medication used to treat atrial fibrillation and atrial flutter by blocking potassium channels and prolonging cardiac repolarization. Hydrochlorothiazide (HCTZ) is a thiazide diuretic commonly prescribed for hypertension and heart failure that works by inhibiting sodium-chloride reabsorption in the distal convoluted tubule of the kidney. Both medications are frequently used in cardiovascular patients, making their potential interaction clinically significant.

Mechanism of Interaction

The interaction between dofetilide and hydrochlorothiazide is primarily pharmacodynamic, involving electrolyte disturbances. Hydrochlorothiazide can cause hypokalemia, hypomagnesemia, and hypocalcemia through increased urinary excretion of these electrolytes. These electrolyte imbalances, particularly low potassium and magnesium levels, can significantly enhance dofetilide's QT-prolonging effects and increase the risk of torsades de pointes. Low potassium levels reduce the repolarizing potassium current that dofetilide already blocks, creating an additive effect on cardiac repolarization delay.

Risks and Symptoms

The primary risk of combining dofetilide with hydrochlorothiazide is an increased likelihood of life-threatening ventricular arrhythmias, particularly torsades de pointes. This risk is significantly elevated when serum potassium falls below 3.5 mEq/L or magnesium below 1.8 mg/dL. Additional risks include prolonged QT interval, syncope, and sudden cardiac death. Patients with pre-existing heart disease, elderly patients, and those with kidney dysfunction face higher risks. The interaction is considered clinically significant and requires active management rather than avoidance of the combination.

Management and Precautions

Close monitoring of serum electrolytes is essential, with potassium levels maintained above 4.0 mEq/L and magnesium above 2.0 mg/dL. Regular ECG monitoring should be performed to assess QT interval changes. Potassium and magnesium supplementation may be necessary. Consider using potassium-sparing diuretics like spironolactone instead of hydrochlorothiazide when possible. If the combination is necessary, start with lower doses and titrate carefully. Patients should be educated about symptoms of arrhythmias and advised to seek immediate medical attention for palpitations, dizziness, or fainting. Regular follow-up appointments should include electrolyte panels and ECG monitoring.

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.

Hydrochlorothiazide interactions with food and lifestyle

Hydrochlorothiazide may increase sensitivity to sunlight, increasing the risk of sunburn and skin reactions. Patients should use sunscreen, wear protective clothing, and limit sun exposure while taking this medication. Alcohol consumption may enhance the blood pressure-lowering effects of hydrochlorothiazide, potentially causing dizziness, lightheadedness, or fainting, especially when standing up quickly. Patients should limit alcohol intake and rise slowly from sitting or lying positions. Excessive salt intake may reduce the effectiveness of hydrochlorothiazide in lowering blood pressure, so patients should follow a low-sodium diet as recommended by their healthcare provider.