Propafenone - instructions for use, dose, side effects, contraindications

Antiarrhythmic drug IC class. It blocks fast sodium channels, causes a dose-dependent decrease in the depolarization rate (phase 0) of the action potential in Purkinje fibers and contractile fibers of the ventricles. Reduces conduction and excitability.

It blocks sodium channels in phase 4, slows it down and depresses the automatism of Purkinje fibers.

Propaphenone acts on the ventricles, and on the drivers of rhythm. However, it is used only for ventricular arrhythmias that threaten life and are resistant to other antiarrhythmic drugs. This is due to its pronounced arrhythmogenic activity.

The drug blocks calcium channels to some extent, and also has β-adrenergic blocking activity. Reduces the automatism of the SA node (a block of sodium and calcium channels in the 4 phase).Lengthens the time spent on the sinoatrial node (SA). Slows phase 0 in the atrioventricular node (sodium channel block) and reduces conduction in AV node.

In usual therapeutic doses, it prolongs the PQ interval and broadens the QRS complex on the ECG in 15-20% of patients. In 2-19% of patients, a pro-arrhythmic effect is noted, incl. ventricular tachycardia; possibly the development of AV blockade II degree. It has a negative inotropic effect, increases pressure in the right atrium, pulmonary arteries and pulmonary capillary wedge pressure, OPSS, resistance of pulmonary vessels, reduces the cardiac index. Beta-adrenergic blocking properties are manifested (when taking high doses) by lowering the maximum heart rate at the peak of physical activity.

Pharmacokinetics:

Absorption when taken orally is almost complete. Significantly expressed the effect of "first passage" through the liver, so the absolute bioavailability is 3.4-10.6%. Almost completely (85-97%) is associated with plasma proteins and internal organs (liver, lungs, etc.). The volume of distribution is 3-4 l / kg. Biotransformation in the liver is carried out with the participation of isoenzymes of the cytochrome P450 system. There are two main phenotypes: in most people (90%), transformations are carried out at a high rate and active metabolites are formed: 5-hydroxypropaphenone,N-depropylpropaphenone. The half-life in these patients is 2-10 hours (an average of 5.5 hours). In the phenotype of slow metabolism, the effect of "first passage" through the liver is expressed to a much lesser extent, the half-life lasts 10-32 hours (an average of 17.2 hours). Excreted at 18.5-38% by the kidneys in the form of metabolites. Most of the dose is excreted with bile (glucuronides and sulfates).

The action begins 30 minutes after ingestion, reaches a peak after 2-3 hours and lasts 8-12 hours.

Indications:Treatment and prevention of supraventricular and ventricular extrasystoles, paroxysmal rhythm disorders - supraventricular tachycardia, incl. with WPW syndrome; in t.ch. flicker and atrial flutter, stable monomorphic ventricular tachycardia (prophylaxis).

ICD-10

IX.I30-I52.I45.6 Syndrome of premature agitation

IX.I30-I52.I47.2 Ventricular tachycardia

IX.I30-I52.I48 Atrial fibrillation and flutter

IX.I30-I52.I49.1 Premature depolarization of the atria

IX.I30-I52.I49.3 Premature depolarization of the ventricles

IX.I30-I52.I49.2 Premature depolarization originating from compound

IX.I30-I52.I49.8 Other specified disorders of heart rhythm

XVIII.R00-R09.R00.8 Other and unspecified heart rate abnormalities

Contraindications:

Hypersensitivity to the components of the drug, intoxication with digoxin.
Refractory heart failure, severe forms of chronic heart failure in the stage of decompensation.
Cardiogenic shock with the exception of arterial hypotension due to tachycardia.
Pronounced bradycardia and arterial hypotension.
Sinoatrial blockade, violation of intrapartum conduction.
Blockade of the legs of the bundle.
Intraventricular bifascicular blockade and AV blockade of II-III degree (without an electrocardiostimulator).
Syndrome of weakness of the sinus node.
Syndrome "tachycardia-bradycardia".
Myocardial infarction.
Age to 18 years (effectiveness and safety not established).
Pronounced electrolyte imbalance, impaired liver or kidney function.
Pregnancy, breast-feeding.

Carefully:

Chronic obstructive pulmonary disease (COPD), myasthenia gravis, incl. m. gravis, heart failure (ejection fraction <30%), cardiomyopathy, arterial hypotension, presence of a permanent or temporary pacemaker in the patient; hepatic cholestasis, hepatic and / or renal failure, a combination with other antiarrhythmic drugs,similar in effect on the electrophysiology of the heart, electrolyte disturbances (mandatory correction before the appointment of propafenone), age over 70 years.

Caution is used in combination with other antiarrhythmics with similar electrophysiological parameters

Pregnancy and lactation:

Action category on the fetus by FDA - C.

Application in pregnancy, especially in the first trimester, is possible only if the expected benefit for the mother exceeds the potential risk to the fetus.

Propaphenone and 5-hydroxypropaphenone penetrate into breast milk in concentrations comparable to those in plasma. Do not use or stop breastfeeding.

Dosing and Administration:

Intravenously drip, inwards (after eating, with a small amount of liquid). Ordinary initial dose inside - 150 mg 3 times / day, in the future it is possible to increase it (every 3-4 days) to 225 mg 3 times a day and even up to 300 mg 3-4 times a day. The maximum daily dose of 1200 mg in 4 divided doses.

In elderly patients apply propafenone in lower doses.

Use in children

Ventricular and supraventricular tachycardia, nodal ectopic tachycardia.

Inside. 12-18 years - begin with 150 mg 3 times a day after meals; if necessary, increase to 300 mg twice a day (for at least 3 days) up to a maximum of 300 mg 3 times a day. With the expansion of the QRS complex, more than 20% reduce the dose or stop receiving before normalizing the ECG. Body weight less than 70 kg - reduce the dose.

Side effects:

From the side of the cardiovascular system: bradycardia, AV dissociation, AV blockade of I degree, decreased blood pressure, ventricular tachyarrhythmias, angina pectoris, ventricular extrasystole, atrial flutter, worsening of heart failure (in patients with reduced left ventricular function), SA and AV blockade, weakness of sinus node, QRS complex expansion , violations of intraventricular conduction, supraventricular tachyarrhythmias; when taken in high doses - orthostatic hypotension, palpitations, cardiac arrest.
From the digestive system: change in taste, dryness and bitterness in the mouth, nausea, vomiting, decreased appetite, a feeling of heaviness in the epigastrium, constipation or diarrhea; rarely - violations of the liver with an increase in the level of transaminases, cholestasis, cholestatic jaundice.

From the side of the central nervous system: headache, dizziness; rarely - blurred vision, diplopia, seizures, extrapyramidal disorders, coma, confusion, memory loss, tinnitus, unusual dreams, emotional disturbance.

From the respiratory system: shortness of breath, bronchospasm, respiratory arrest,

From the laboratory indicators: leukopenia, thrombocytopenia, anemia, neutropenia, agranulocytosis, increased bleeding time, the appearance of antinuclear antibodies.

Allergic reactions: skin rash, itching, exanthema, reddening of the skin, urticaria, lupus-like syndrome.

Other: weakness, bronchospasm, hemorrhagic rashes on the skin, electrolyte disorders, impotence.

Overdose:

Symptoms of intoxication can arise when the dose is twice taken, twice the daily dose, and appear after an hour, a maximum of several hours.

Symptoms: convulsions, hypotension, nausea, dry mouth, vomiting, mydriasis, bradycardia, atrial and intraventricular conduction disorders, ventricular arrhythmias of high grades, drowsiness or psychomotor agitation, confusion, extrapyramidal disorders,prolongation of QT interval, SA and AV block, paroxysms of polymorphic ventricular tachycardia, asystole, coma, convulsions, delirium, pulmonary edema

Treatment: defibrillation, infusion of dobutamine, dopamine and isoproterenol, diazepam, possible IVL, indirect cardiac massage, gastric lavage. Hemodialysis is ineffective.

Interaction:

Digoxin, metoprolol, propranolol, warfarin, theophylline, ciclosporin - increase of their plasma concentration with simultaneous application with propafenone.

Other antiarrhythmic drugs, β-adrenoblockers - an increase in cardiodepressive action.

With simultaneous use with beta-blockers, tricyclic antidepressants, an antiarrhythmic effect may increase, with local anesthetics, an increased risk of CNS damage.

Lidocaine - increased side effects on the central nervous system and cardiodepressant effect.

Orlistat - reduced absorption of propafenone.

Amiodarone increases the risk of developing tachycardia such as pirouette.

Drugs that inhibit SA and AV sites and have a negative inotropic effect, increase the risk of side effects.

The agents extending the Q-T interval (antiarrhythmics, macrolides, fluoroquinolones, phenothiazines,cisapride, tricyclic antidepressants, etc.) - potentiation of the effect on the Q-T interval.

Phenobarbital, phenytoin, rifabutin, rifampicin (inducers of liver enzymes) - decreased plasma concentrations of propafenone.

Quinidine, cimetidine (inhibition of CYP2D6) - increased plasma concentrations of propafenone.

Cimetidine is an increase in the plasma concentration of propafenone.

Drugs that depress bone marrow hematopoies, increase the risk of myelosuppression.

Special instructions:

Treatment should be started in a hospital, because the risk of arrhythmogenic action associated with the use of propafenone is increased. It is recommended that the previous antiarrhythmic therapy should be discontinued before the treatment with propafenone begins at a time equal to 2-5 half-lives.

Propaphenone is characterized by pronounced individual differences in the concentration of active substance in the blood plasma, therefore, careful selection of doses for each patient is recommended.

Because of the bitter taste, the tablets are swallowed whole, with water. To reduce the unpleasant taste, the tablets can be crumbled and dissolved in water, adding sugar. Take immediately and rinse the mouth.

Treatment should be carried out under the control of electrolyte balance (especially the level of potassium), ECG and blood pressure. If the PQ interval is extended and the QRS complex is expanded by 50% or more, careful monitoring of the patient is necessary: in the case of an increase in PQ by more than 0.3 s and QRS by more than 0.2 s, the occurrence of a two-beam blockade or AV blockade of II-III degree it is necessary to reduce the dose or cancel the drug. It is recommended to periodically determine the activity of transaminases, antinuclear antibodies. Patients with an implanted pacemaker should take into account the increase in the threshold of defibrillation and electrocardiostimulation, which makes it mandatory to correct the parameters of the pacemaker. If liver function is impaired (cumulation is possible), it is used in doses of 20-30% of usual.

Impact on the ability to drive vehicles and manage mechanisms

During the treatment period it is necessary to abstain from driving motor vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Instructions

Propafenone (Propaphenonum)