Is dose adjustment of mexiletine required for treating myotonia in patients with impaired renal function (Renal Impairment), with or without dialysis?

Mexiletine Dosing in Renal Impairment for Myotonia Treatment

No dose adjustment of mexiletine is required for the treatment of myotonia in patients with renal impairment (stages 1-5), with or without dialysis. 1, 2, 3

Pharmacokinetic Rationale

Mexiletine is primarily eliminated through hepatic metabolism, with minimal renal excretion. This pharmacokinetic profile makes it suitable for patients with impaired kidney function without requiring dose modifications:

• The FDA drug label states that "in general, patients with renal failure will require the usual doses of mexiletine hydrochloride" 1
• Pharmacokinetic studies have demonstrated that:
  • There is no correlation between mexiletine elimination half-life or oral clearance and creatinine clearance 2
  • The plasma kinetics of mexiletine remain unchanged when creatinine clearance is above 10 ml/min 3
  • Mexiletine is not significantly removed during dialysis procedures 2, 4

Dosing Recommendations for Myotonia in Renal Impairment

For patients with myotonia and renal impairment:

1. Initial dosing: Start with the standard dose of 200 mg every 8 hours with food or antacid
2. Titration: Adjust dose in 50-100 mg increments based on clinical response and tolerability
3. Maintenance dosing: Most patients achieve satisfactory control with 200-300 mg every 8 hours
4. Maximum dosing: Do not exceed 1200 mg/day due to increased risk of CNS side effects 1

For patients on dialysis:

• No supplemental doses are needed after dialysis sessions 2
• Some studies suggest a slightly reduced dosage of 400-600 mg/day may be appropriate for end-stage renal disease patients on dialysis 4

Monitoring Considerations

While dose adjustment is not required, careful monitoring is recommended:

• Clinical efficacy: Assess improvement in myotonia symptoms
• Side effects: Monitor for CNS side effects, which increase with total daily dose
• ECG monitoring: Consider periodic ECG monitoring, especially when initiating therapy
• Drug interactions: Be aware that certain concomitant medications may affect mexiletine plasma levels 1

Special Considerations

• Hepatic impairment: Unlike renal impairment, patients with severe liver disease may require lower doses and must be monitored closely 1
• Right-sided heart failure: May reduce hepatic metabolism and require dose reduction 1

Clinical Efficacy in Myotonia

Mexiletine has demonstrated efficacy in treating myotonia in patients with myotonic dystrophy and non-dystrophic myotonia 5. While alternative treatments like lamotrigine have shown promise 6, mexiletine remains a standard treatment option for myotonia regardless of renal function.

In conclusion, mexiletine can be safely administered at standard doses to patients with myotonia who have renal impairment, including those on dialysis, with appropriate monitoring for efficacy and side effects.