mexiletine hydrochloride

CLINICAL USE

Ventricular arrhythmias, especially after a myocardial infarction

DOSE IN NORMAL RENAL FUNCTION

Oral: 400 mg loading dose, followed by 200–250 mg 3–4 times daily commencing 2 hours after the loading doseIV injection: 100–250 mg at a rate of 25 mg/minute with ECG monitoring, followed by an infusion of 250 mg as a 0.1% solution over 1 hour, 125 mg/hour for 2 hours then 500 micrograms/minute thereafter

PHARMACOKINETICS

Molecular weight :215.7

%Protein binding :50–70

%Excreted unchanged in urine : 10

Volume of distribution (L/kg) :5–7

half-life – normal/ESRD (hrs) :5–17/16

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : 50–75% of normal dose and titrate according to response

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Dialysed. Dose as in GFR

<10 : mL/min

CAV/VVHD :Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Analgesics: opioids delay absorption

Anti-arrhythmics: increased myocardial depression with any combination of anti-arrhythmics

Antidepressants: metabolism inhibited by fluvoxamine (increased toxicity)Antihistamines: increased risk of ventricular arrhythmias with mizolastine – avoid concomitant use

Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval

Antivirals: possibly increased risk of arrhythmias with ritonavir

Beta-blockers: increased myocardial depression

Diuretics: action of mexiletine antagonised by hypokalaemia5HT 3 antagonists increased risk of ventricular arrhythmias with dolasetron – avoid concomitant use; caution with tropisetron

ADMINISTRATION

Reconstition

–

Route

IV infusion

, oral

Rate of Administration

Variable

Comments

Add 250–500 mg mexiletine to 500 mL of infusion solution, e.g. sodium chloride 0.9%, glucose 5%, sodium bicarbonate 8.4%, sodium lactate, sodium chloride 0.9% with potassium chloride 0.3% or 0.6%

OTHER INFORMATION

Mexiletine has a narrow therapeutic index. Its therapeutic effect has been correlated with plasma concentrations of 0. 5–2 micrograms per mLMexiletine is metabolised in the liver and is excreted in the urine, mainly in the form of metabolitesRate of elimination increased with acidic urineInjection can be given orally; however, due to local anaesthetic effect, care needed with hot foods

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