Onset of Action for Mexiletine in PVC Suppression
Mexiletine begins to exert therapeutic effects within 30 minutes to 2 hours after oral administration, with peak plasma concentrations reached in 2-3 hours. 1
Pharmacokinetic Timeline
When rapid control is needed, a loading dose of 400 mg produces onset of therapeutic effect within 30 minutes to 2 hours. 1 This is followed by 200 mg eight hours later to maintain therapeutic levels. 1
For standard dosing without a loading dose:
- Peak blood levels occur 2-3 hours after oral administration 1, 2
- Therapeutic plasma levels (≥0.5 mcg/mL) required for antiarrhythmic response are typically achieved within this timeframe 1
- Bioavailability is approximately 90%, with rapid and complete absorption 1, 2
Clinical Response Timeline for PVC Suppression
The actual suppression of PVCs follows the pharmacokinetic profile, with observable effects beginning 30 minutes to 2 hours after dosing. 1 However, optimal therapeutic response requires:
- A minimum of 2-3 days between dose adjustments to assess full therapeutic effect 1
- Clinical and electrocardiographic evaluation (including Holter monitoring) to determine adequate antiarrhythmic effect 1
Dosing Strategy for PVC Control
Initial therapy should start at 200 mg every 8 hours with food or antacid when rapid control is not essential. 1 The dose can be adjusted in 50-100 mg increments. 1
Most patients achieve satisfactory control with 200-300 mg every 8 hours. 1 If response is inadequate at 300 mg every 8 hours and the patient tolerates the medication well, 400 mg every 8 hours may be tried, though maximum daily dose should not exceed 1200 mg due to increased CNS side effects. 1
Important Clinical Considerations
Absorption may be delayed in certain clinical situations:
- Acute myocardial infarction slows gastric emptying and reduces absorption rate 1
- Narcotics, atropine, and magnesium-aluminum hydroxide slow absorption 1
- Metoclopramide accelerates absorption 1, 2
The elimination half-life is approximately 10-12 hours in normal subjects 1, 3, but this is prolonged to approximately 25 hours in patients with moderate to severe liver disease. 1
Therapeutic plasma range is 0.5-2 mcg/mL, with CNS adverse effects increasing when levels exceed 2 mcg/mL. 1
Efficacy Data
In clinical trials, approximately 30% of patients achieved 70% or greater reduction in PVC count 1, with efficacy rates of 60-80% for spontaneous ventricular arrhythmia suppression reported in other studies. 4 However, efficacy for PVC suppression was only 43% in one comparative trial, with 50% of patients requiring discontinuation due to gastrointestinal or CNS side effects. 5
Long-term studies demonstrate that 69-80% of initial responders maintain the same level of VPC suppression during extended treatment periods. 6