Propafenone Hydrochloride

Pharmacological properties

Propaphenone hydrochloride (1- [2- [2-hydroxy-3-propylamino) propoxy] phenyl] -3-phenyl-1-propanone hydrochloride) is an antiarrhythmic drug of class IC with a moderately pronounced β-adrenergic blocking effect. It has a direct membrane stabilizing effect on myocardiocytes, inhibits fast sodium channels, reduces the maximum rate of depolarization of myocardiocytes and their excitability. slows down the conduction of the pulse in the atria, the av node, especially in the system of the bundle of His and the fibers of Purkinje. propafenone increases the interval p – r and slightly qrs. in the presence of additional pathways it increases their refractory period and completely blocks the conduct of excitation in both antegrade and retrograde directions. the drug increases the effective refractory period of the av node and ventricles.

Absorption by ingestion is almost complete (95%). C_max in blood plasma is achieved after 2-3 hours. Propanorm exhibits a dose-dependent bioavailability. Almost completely (85–97%) binds to plasma proteins and internal organs (liver, lungs, etc.). It undergoes biotransformation in the liver using the cytochrome P450 system, the activity of which is genetically determined. There are 2 main phenotypes - in most (90%) people, biotransformation occurs rapidly with the formation of active metabolites (5-hydroxypropaphenone, N-depropylpropaphenone, etc.). T_½ in such patients it is 2-10 hours (on average 5.5 hours). With the slow metabolism phenotype, the effect of the primary passage through the liver is much less pronounced, T_½ is 10–32 hours (on average - 17.2 hours). The effect develops approximately 1 hour after ingestion, reaches its maximum severity after 2-3 hours and lasts 8-12 hours. The range of therapeutic concentrations of propafenone in blood plasma is 0.5–2 mg / L.

About 10% of the drug is excreted in the urine in the form of metabolites; most (87%) of the dose is excreted in the bile (in the form of propafenone glucuronides and sulfates).

Indications

Prevention and elimination of arrhythmias - all types of supraventricular and ventricular extrasystoles, atrial fibrillation, supraventricular tachyarrhythmias, including in patients with additional ways of conducting excitation (wpw cm, clerk-levy syndrome-christesco).

Application

For adults, the dose and frequency of administration are set individually and corrected under the control of the level of hell and ecg. with an increase in the duration of the qrs complex and the q – t interval by more than 20% of the initial value, it is necessary to reduce the dose or temporarily discontinue the drug until the indicators normalize. therapeutic dose for patients weighing 70 kg is 450-600 mg / day (150 mg 3 times a day or 300 mg 2 times a day). the maximum daily dose is 900 mg. patients with lower body weight are accordingly reduced the dose.

The drug is taken after meals, the tablets are swallowed without chewing, washed down with a sufficient amount of water.

Contraindications

Hypersensitivity to propafenone, cardiogenic shock (except shock caused by arrhythmia), heart failure, sinus bradycardia (heart rate 50 beats / min), sinus node weakness, arterial hypotension (hell 100/70 mm Hg), conduction disturbance ( sinoatrial, av-block II – III degree, blockade of the legs of the bundle of His), myasthenia gravis, severe electrolyte imbalance, bronchospasm, severe obstructive pulmonary disease, impaired liver and kidney function, pregnancy and lactation (propafenone passes into breast milk), in stems 3 months after acute myocardial infarction and in patients with reduced cardiac output (except for patients with atrial fibrillation, a life-threatening).

Side effects

When taking propanorm in a high dose, anorexia, a feeling of fullness of the stomach, nausea, vomiting, taste disturbance, dry mouth can occur, in some cases - dizziness, headache, weakness, decreased visual acuity, sleep disturbance, extrapyramidal disorders, coma, confusion , memory loss. allergic reactions are sometimes noted.

In elderly patients, orthostatic reactions may occur, sometimes bradycardia, impaired AV conduction (AV block, QRS complex increase), ventricular extrasystole and tachycardia, atrial flutter, AV dissociation, sinus node weakness, cardiac arrest; angina attacks, symptoms of heart failure may occur or intensify. Cholestasis, decreased potency, anemia, hemorrhagic rash, neutropenia, increased bleeding time, leukopenia, thrombocytopenia are extremely rare. The composition of peripheral blood normalizes after discontinuation of the drug.

special instructions

Use with extreme caution in patients with an implanted pacemaker. at the beginning of treatment with propanorm, constant ECG control is required.

The benefit / risk ratio should be weighed in patients with degree I AV blockade, severe forms of obstructive bronchopulmonary disease, AD, electrolyte imbalance, liver failure, and myasthenia gravis. In patients with liver failure, the bioavailability of propafenone is increased by 70%, therefore, such patients should reduce the dose and constantly monitor laboratory parameters. In patients who are treated for a long time with anticoagulants and antidiabetic agents, clinical and laboratory monitoring is required. It should be used with caution in patients with a history of myocardial infarction and should not be prescribed in the first 3 months after acute myocardial infarction. If during treatment there is a sinoauricular block or severe AV block, or extrasystole (frequent or polymorphic), treatment with Propanorm should be discontinued.

There is no clinical experience with the use of the drug in children.

During treatment with the drug, you should avoid driving vehicles and performing work requiring increased attention and speed of psychomotor reactions. If surgical intervention is necessary, it is necessary to take into account that the introduction of local anesthetics can enhance the effect of propafenone. It is not recommended to use the drug during lactation. Also not recommended for children under the age of 15 years.

Interactions

With the simultaneous use of local anesthetics, as well as drugs that reduce heart rate and myocardial contractility (β-adrenergic receptor blockers, tricyclic antidepressants), it is necessary to take into account the possibility of a mutual enhancement of cardiodepressive action.

The simultaneous administration of ritonavir increases the incidence of side effects of Propanorm. Combined use with other antiarrhythmic drugs is undesirable.

Cases of increasing the concentration of propranolol, metoprolol in blood plasma with the simultaneous use of propafenone are described. Quinidine promotes an increase in the plasma level of propafenone with a decrease in the level of its main metabolite, 5-hydroxypropaphenone.

There are reports of an increase in the level of propafenone in blood plasma with its simultaneous use with cimetidine, an increase in prothrombin time with combined use with indirect anticoagulants. Propanorm increases the plasma concentration of cyclosporine, digoxin (the risk of developing glycoside intoxication increases), as well as theophylline and diltiazem. Potentiates the effect of warfarin, inhibiting its biotransformation. Rifampicin reduces the effect of Propanorm.

Overdose

It can be manifested by anorexia, a feeling of fullness of the stomach, nausea, vomiting, impaired taste sensitivity, headache, decreased visual acuity, extrapyramidal disorders, coma, confusion, amnesia. orthostatic reactions, bradycardia, impaired conduction of the av node (av blockade, increased qrs complex), ventricular tachycardia, atrial flutter, av dissociation, sinus node weakness, cardiac arrest may occur; symptoms of heart failure may occur and intensify, convulsions develop. when symptoms of an overdose appear, reduce the dose or cancel the drug.

Treatment: iv lactate and potassium chloride are administered iv. Sometimes there is a need for the introduction of glucagon, epinephrine and the use of pacemaker.

Storage conditions

In the inner packaging and box at a temperature of 15-25 ° C.