Management of Two Missed Doses of Mexiletine in an Asymptomatic Patient
Resume mexiletine at the previously prescribed dose (typically 200-300 mg every 8 hours) with the next scheduled dose, without attempting to "catch up" or double-dose, and continue regular monitoring for arrhythmia recurrence over the next 48-72 hours. 1
Immediate Action
Do not take extra doses to compensate for the missed medications, as mexiletine has a narrow therapeutic window and dose-related toxicity that includes CNS effects (lightheadedness, tremor, confusion, seizures) and cardiovascular complications (heart block, hypotension, proarrhythmic effects). 2, 3
Resume the regular dosing schedule with the next dose due, taking mexiletine with food or antacid to minimize gastrointestinal side effects. 1
Given mexiletine's half-life of 10-14 hours, missing two consecutive doses (16-24 hours depending on the regimen) means plasma levels have declined but not been completely eliminated. 2
Clinical Monitoring Requirements
Monitor closely for arrhythmia recurrence over the next 48-72 hours, as the therapeutic effect may be temporarily diminished:
Check for return of symptoms that prompted mexiletine therapy initially (palpitations, presyncope, syncope). 2
Consider obtaining an ECG if the patient was being treated for documented ventricular tachycardia or if any cardiac symptoms develop. 1
Patients with life-threatening ventricular arrhythmias (VT/VF) require more intensive monitoring, potentially including telemetry or Holter monitoring. 2, 4
Key Safety Considerations
The asymptomatic status is reassuring but does not guarantee arrhythmia suppression, as mexiletine's primary indication is for ventricular arrhythmias that may be clinically silent between episodes:
Mexiletine suppresses ventricular ectopy in only 25-79% of patients, and breakthrough arrhythmias can occur even on therapy. 5
The drug has a relatively low proarrhythmic potential compared to other antiarrhythmics, but this risk still exists, particularly during periods of subtherapeutic levels. 5, 3
Common Pitfalls to Avoid
Never administer a loading dose or double-dose to rapidly restore therapeutic levels, as this significantly increases the risk of CNS toxicity (tremor, ataxia, confusion, seizures) and cardiovascular complications. 1, 3
Do not assume the patient can safely remain off mexiletine just because they are currently asymptomatic—the underlying arrhythmia substrate remains and may manifest unpredictably. 6, 4
Avoid switching to twice-daily dosing immediately after missed doses without first re-establishing stable arrhythmia control on the every-8-hour regimen. 1
Patient Education and Prevention
Reinforce the critical importance of medication adherence for antiarrhythmic therapy:
Missing doses of mexiletine can lead to breakthrough ventricular arrhythmias, which may be life-threatening depending on the underlying indication. 6, 4
Use pill organizers, smartphone reminders, or other adherence aids to prevent future missed doses. 2
Instruct the patient to contact their provider if they miss more than one dose or develop any cardiac symptoms. 1
Special Circumstances Requiring Dose Adjustment
If the patient has developed any of the following since starting mexiletine, do not simply resume the previous dose without reassessment:
- New or worsening heart failure (reduces hepatic metabolism and clearance). 1, 7
- Acute liver disease (requires dose reduction and close monitoring). 1, 7
- Recent myocardial infarction (prolongs elimination half-life). 7
- Addition of drugs that affect CYP metabolism or compete for hepatic clearance. 1
Long-term Management
Schedule follow-up within 1-2 weeks to assess: