MEXILETINE HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MEXILETINE HYDROCHLORIDE (MEXILETINE HYDROCHLORIDE).
Class Ib antiarrhythmic agent; blocks sodium channels, decreases action potential duration, and increases the ratio of refractory period to action potential duration.
| Metabolism | Hepatic via CYP2D6 and CYP1A2; extensive first-pass metabolism. |
| Excretion | Renal: ~90% (10% unchanged, remainder as metabolites); Biliary/fecal: <10% |
| Half-life | 10-12 hours (prolonged in hepatic impairment, acute MI, and urine pH >6.5) |
| Protein binding | 50-70% (primarily to alpha-1-acid glycoprotein, albumin) |
| Volume of Distribution | 5-9 L/kg (extensive tissue distribution, e.g., heart, liver) |
| Bioavailability | Oral: 80-95% (first-pass metabolism <10%) |
| Onset of Action | Oral: 30-120 minutes; IV: 5-10 minutes |
| Duration of Action | Oral: 6-12 hours; IV: 1-4 hours (dose-dependent) |
200–300 mg orally every 8 hours; maximum 1200 mg/day. Loading dose: 400 mg orally, then 200 mg after 8 hours if needed. IV use is investigational. Administer with food to reduce GI upset.
| Dosage form | CAPSULE |
| Renal impairment | GFR ≥10 mL/min: No adjustment. GFR <10 mL/min: Reduce dose by 50% or extend interval to every 12 hours. Hemodialysis: Administer after dialysis on dialysis days; no supplemental dose needed. Dose based on creatinine clearance (CrCl) using Cockcroft-Gault equation. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose by 25–50%. Child-Pugh C: Reduce dose by 50% or avoid use. Monitor plasma levels and toxicity (e.g., CNS, cardiac). |
| Pediatric use | Safety and efficacy not established. Extrapolated dosing: 1.5–5 mg/kg orally every 8 hours; maximum 15 mg/kg/day. Use only under expert guidance with therapeutic drug monitoring. Contraindicated in structural heart disease. |
| Geriatric use | Start at lower end of dosing range (150–200 mg every 8 hours). Use with caution due to age-related renal/hepatic decline, increased risk of QT prolongation, and fall risk from dizziness/ataxia. Monitor renal function and electrolytes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MEXILETINE HYDROCHLORIDE (MEXILETINE HYDROCHLORIDE).
| Breastfeeding | M/P ratio unknown. Mexiletine is excreted into breast milk in small amounts; estimated infant dose <1% of maternal weight-adjusted dose. Data suggest compatible with breastfeeding, but monitor infant for bradycardia and feeding difficulties. |
| Teratogenic Risk | First trimester: Limited data; no major malformation signal in small retrospective studies. Second and third trimesters: No specific fetal toxicity reported; may cause fetal bradycardia, especially with maternal toxicity. Use only if clearly needed. |
■ FDA Black Box Warning
None
| Serious Effects |
["Cardiogenic shock","Second- or third-degree AV block (without pacemaker)","Hypersensitivity to mexiletine or similar local anesthetics"]
| Precautions | ["May worsen or provoke ventricular arrhythmias (proarrhythmic effect)","Use with caution in patients with hepatic impairment","Monitor for CNS effects (tremor, dizziness, ataxia)","May cause confusion or seizures at high doses"] |
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| Fetal Monitoring |
| Monitor maternal heart rate, ECG, and drug levels (therapeutic range 0.5-2 mcg/mL). Fetal: heart rate monitoring during late pregnancy for bradycardia. Assess fetal growth with ultrasound if prolonged use. |
| Fertility Effects | No known significant impact on human fertility. Animal studies show no adverse effects on reproductive parameters. |