Antiarrhythmic drug class Ic. It stabilizes cell membranes and inhibits the rapid sodium current. It releases the speed of phase 0 of the action potential. Extends the duration of the action potential of the cardiac muscle cells, shortens the duration of the action potential in Purkini fibers. It has a negative dromotropic effect. Refraction time in the vestibule, atrio-ventricular node and mosquitoes is extended. In patients with WPW, propafenone lengthens refraction time in additional conduction pathways. Propafenone also has poor β-blocking properties. When administered orally, it is almost completely absorbed from the gastrointestinal tract. It is subject to the first-pass effect. After a single dose, the bioavailability is about 50%. Achievemax within 3.5 h. The therapeutic effect lasts about 8 h. The steady state is reached after 3-4 days, when the bioavailability rises to almost 100%. About 95% is bound to plasma proteins. It is metabolized in the liver. In more than 90% of patients, the drug is rapidly and extensively metabolised to two active metabolites: 5-hydroxypropafenone - with the participation of the CYP2D6 isoenzyme and N-depropylpropafenone (norpropafenone) - with the participation of CYP3A4 and CYP1A2. The antiarrhythmic activity of these metabolites is similar to the parent compound, but their concentration in blood is 20% lower. In <10% of patients, propafenone metabolism is slower - 5-hydroxypropafenone is not formed or formed in a minimal amount. T0,5 is 2-10 hours in rapidly metabolised patients and about 10-32 hours in slow metabolizing patients. The drug is excreted in the urine as metabolites.
Contraindications:
Hypersensitivity to propafenone or any of the excipients. Serious heart disease such as: decompensated congestive heart failure, cardiogenic shock (excluding shock caused by arrhythmia). Symptomatic severe bradycardia. Disorders of sinus node function, vestibular conduction disturbances, second or third-degree atrioventricular block, bundle branch block or distal block in patients without a pacemaker. Severe hypotension. Disturbances in the slow-electrolyte balance. Severe obstructive pulmonary disease.
Precautions:
The safety and efficacy of propafenone in patients <18 years has not been established - do not use. Caution should be used in patients with hepatic impairment (increased bioavailability and T0,5 drug), renal failure (slower drug elimination), pacemaker (propafenone treatment may affect the pacing threshold and the sensitivity of the implanted pacemaker, check the operation of the pacemaker and, if necessary, program it again), myasthenia gravis (the drug may worsen its symptoms), in patients with significant left ventricular dysfunction - LVEF <35%, significant damage to the myocardium and elderly patients. During propafenone treatment there is a possibility of passage of paroxysmal atrial fibrillation in atrial flutter with an accompanying conduction block in a 2: 1 or 1: 1 ratio. During treatment, ECG should be performed regularly and blood pressure should be monitored. The preparation contains lactose - do not use in patients with hereditary galactose intolerance, Lapp lactase deficiency or malabsorption of glucose-galactose.
Pregnancy and lactation:
Propafenone crosses the placenta barrier - do not use during pregnancy except for absolute necessity. It can be excreted into breast milk - do not use during breast-feeding.
Orally. Treatment of ventricular tachyarrhythmia should be performed in a hospital setting. Dosage should be individually selected. The lowest effective dose should be used. Initially, patients with a body weight of about 70 kg, apply 150 mg 3 times a day. In the case of ineffectiveness, the daily dose may be increased, not more often than every 3-4 days, to a dose of 300 mg 2 times a day, or even 300 mg 3 times a day, on condition of strict cardiac control. The safety of the drug at a dose above 900 mg / day has not been established. For patients weighing <70 kg, the dose should be lower. In elderly patients and patients with significant left ventricular dysfunction (ejection fraction <35%) or myocardial damage, treatment should be started at low doses. Extreme caution should be used if a dose increase is required after 5 to 8 days of treatment. In patients with impaired liver or kidney function the dose should be adjusted to the possibility of elimination of the drug from the body. The preparation should be taken after a meal, washed down with water.