Included in the formulation
АТХ:C.01.B.B.02 Mexiletin
C.01.B.B Antiarrhythmic drugs Ib class
Pharmacodynamics:Slightly reduces the maximum depolarization rate due to the interaction of the ionized fraction with fast sodium channels, inhibits intracardiac conduction. With an increase in the concentration of extracellular potassium ions and / or a decrease in the membrane potential, the inhibitory effect on the fast channels is enhanced. Conductivity disorder in fibers having a reduced rapid response component is more pronounced compared to cells having a constant fast response. Reduces the duration of the action potential due to the blockage of sodium current inside the cell in the plateau phase. The shortening of repolarization is accompanied by a decrease in the effective refractory period; the degree of shortening of repolarization is greater than the degree of decrease in refractoriness (relative increase in refractoriness). At normal concentrations, reduces the slope of the 4-phase depolarization in fibers that have normal automatism. In high concentrations, it is able to suppress pathological automatism. It can block the trigger activity in the Purkinje fibers due to delayed post-potentials.Effective in the treatment of ventricular arrhythmias in patients with acute myocardial infarction.
Pharmacokinetics:Absorption from the gastrointestinal tract reaches 90%, the onset time Cmax - 2-4 hours. The therapeutic concentration in the blood is 0.75-2 μg / ml, the toxic concentration is more than 2 μg / ml. 55% of the circulating vasculature mexylethane binds to plasma proteins. After intravenous administration, the concentration in the plasma rapidly decreases, the state of stable equilibrium develops within 1-3 days. Half-life varies within 8-20 hours. Completely metabolized in the liver with the formation of inactive metabolites. It is excreted mainly with bile, 10% - kidneys in unchanged form.
Indications:Ventricular extrasystole, paroxysmal ventricular tachycardia, prevention of ventricular fibrillation (including in the acute period of myocardial infarction).
IX.I30-I52.I47.2 Ventricular tachycardia
IX.I30-I52.I49.0 Fibrillation and flutter of the ventricles
IX.I30-I52.I49.3 Premature depolarization of the ventricles
IX.I30-I52.I49.2 Premature depolarization originating from compound
IX.I30-I52.I49.1 Premature depolarization of the atria
Contraindications:Hypersensitivity(including local anesthetics from the amide group), atrioventricular blockade of the II-III degree, cardiogenic shock, severe heart failure, bradycardia below 50 beats per minute, hypotension, sinus node weakness syndrome, conduction system damage, impaired liver and kidney function, epilepsy, mental illness, pregnancy and lactation.
Carefully:Due to the presence of a negative inotropic effect (although insignificant), care should be taken when prescribing to patients with severe heart failure. It is not recommended to quickly increase the dose (the interval should be at least 2-3 days). If the liver function is disrupted, the initial daily dose is halved. The increase in activity of aspartic transaminase serves as an indication for discontinuing treatment. When switching from antiarrhythmic drugs of class Ia to mexiletine intervals: 6-12 hours after the last dose of quinidine and disopyramide, 3-6 hours - novocainamide; the infusion of lidocaine is stopped at the same time as the first dose of mexiletine is administered, but the system for infusion is not detached from the patient (there may be a relapse of the arrhythmia).In connection with the risk of developing life-threatening arrhythmias, the abolition of previous antiarrhythmic therapy is performed in a stationary setting.
Pregnancy and lactation:Recommendations FDA category C. Adequate and well-controlled studies in humans have not been conducted. In animals in doses 4 times higher than the maximum for ingestion for humans, caused an increased frequency of fetal resorption, but not teratogenicity. Penetrates into breast milk in concentrations comparable to those in plasma. It should not be used during pregnancy and breastfeeding.
Dosing and Administration:In urgent situations, intravenously injected or drip. The initial dose is 170 μg / kg / min. Then within 3 hours, the infusion in a dose of 30 μg / kg / min, which corresponds to 405 mg with a patient's body weight of 75 kg. After that, up to 12 hours or more is administered at a dose of 8 μg / kg / min, i.e. 37.5 mg / h. When switching to oral administration, the first dose of mexiletine 200 mg should be taken 1 hour before the end of the infusion. The average daily maintenance dose for oral administration is 600 mg. The maximum dose is 1200 mg. The frequency of reception depends on the dosage form used.
It is not recommended to increase the dose quickly (the interval should be at least 2 days).
If the liver function is disturbed, the initial daily dose is reduced by 2 times. When the activity of aspartate aminotransferase increases mexiletine should be canceled.
Use in children: efficacy and safety not studied.
Side effects:Nervousness, insomnia, paresthesia, dizziness, headaches, muscle trembling, impaired coordination of convulsions, convulsions, visual disturbances, chest pain, peripheral edema, increased ventricular arrhythmia, nausea, vomiting, heartburn, liver dysfunction, lowering blood pressure, bradycardia , leukopenia, thrombocytopenia, skin rashes.
Overdose:Symptoms: arterial hypotension, bradycardia, conduction disorders, nausea, paresthesia, epileptoid seizure, dysarthria, diplopia, nystagmus, impaired consciousness.
Treatment: symptomatic. To accelerate the excretion of the use of drugs that oxidize urine (
ammonium chloride,
ascorbic acid). Intravenous injection of 0.5-1 mg of atropine. Hemodialysis is indicated.
Interaction:Antacid preparations,
acetazolamide (alkalinization of urine) - a decrease in renal excretion of mexiletine, an increase in its concentration in the blood plasma.
Other antiarrhythmic drugs are an intensification of cardiodepressive action.
Increase in plasma concentration and the likelihood of toxic effects on the central nervous system caffeine, theophylline.
Metoclopramide - increased absorption of mexiletine.
Phenobarbital,
phenytoin,
rifampicin (inductors CYP2D6) - decreased plasma concentrations of mexiletine.
Fluvoxamine (inhibitor CYP1A2) - increased plasma concentration of mexiletine.
Special instructions:Ineffective in atrial arrhythmias due to short duration of action potentials.
Effective in ventricular rhythm disorders in patients with chronic obstructive pulmonary disease, with chronic bronchial obstruction in the decompensation stage cor pulmonale (in the intensive care unit - 200 mg intravenously + 200 mg orally, in the next 48 hours, 200 mg every 8 hours).