Does maxiletine (antiarrhythmic medication) affect blood pressure?

Does Mexiletine Affect Blood Pressure?

Mexiletine has minimal effect on blood pressure in most patients, but can cause hemodynamic deterioration including increased filling pressures and decreased cardiac output in patients with severe left ventricular dysfunction. 1, 2, 3

Blood Pressure Effects in General Population

• Mexiletine produces no significant change in blood pressure or heart rate in patients with normal or mildly impaired cardiac function. 1, 4

• In controlled trials comparing mexiletine to other antiarrhythmics, mexiletine had little effect on blood pressure, whereas procainamide induced a significant drop in systolic pressure. 2

• The FDA label explicitly states that hemodynamic studies show blood pressure and pulse rate remain essentially unchanged with mexiletine in most patients. 1

Critical Exception: Severe Heart Failure

In patients with severe left ventricular dysfunction, mexiletine causes marked hemodynamic deterioration that is clinically significant and potentially dangerous. 3

• In 20 patients with severe chronic heart failure given a 400 mg oral loading dose, mexiletine caused:

  • 25% decrease in stroke work index (P < 0.001) 3
  • 15% decrease in cardiac output (P < 0.001) 3
  • 37% increase in left ventricular filling pressure (P < 0.001) 3
  • 20% increase in systemic vascular resistance (P < 0.05) 3
  • Clinical deterioration with dyspnea at rest in 5 patients (25%) 3

• The hemodynamic deterioration is dose-dependent: patients with plasma mexiletine levels above 1.3 mcg/mL experienced a 38% decrease in stroke work index, compared to only 13% in those with lower levels. 3

Mechanism and Cardiac Effects

• Mexiletine is a Class IB antiarrhythmic that blocks sodium channels, similar to lidocaine, with minimal negative inotropic effect compared to Class IA agents like procainamide or disopyramide. 1, 5

• The drug has mild depression of myocardial function similar to lidocaine, which occasionally manifests following intravenous administration in patients with cardiac disease. 1

• Hemodynamic studies show small, usually not statistically significant, decreases in cardiac output and increases in systemic vascular resistance, but no significant negative inotropic effect in patients without severe dysfunction. 1

Clinical Implications and Monitoring

Avoid mexiletine in patients with severe congestive heart failure or significantly reduced ejection fraction due to risk of hemodynamic collapse. 3

• For patients with moderate cardiac dysfunction, start with lower doses and monitor closely for signs of hemodynamic deterioration including dyspnea, increased filling pressures, or decreased cardiac output. 3

• The therapeutic plasma concentration range is 0.5 to 2.0 mcg/mL, but aim for the lower end of this range in patients with any degree of left ventricular dysfunction to minimize cardiodepressant effects. 3

Drug Interactions Affecting Blood Pressure

• Tizanidine can cause significant hypotension and bradycardia when combined with CYP1A2 inhibitors including mexiletine, as mexiletine is metabolized by CYP1A2. 6

• This interaction is clinically relevant and should be avoided or monitored closely if concurrent use is necessary. 6