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

Similar drugsTo uncover

Dosage form: & nbspcoated tablets

Composition:

1 tablet, film-coated, contains:

Core:

active substance: propafenone hydrochloride 150,000 mg;

auxiliary substancesa: lactose monohydrate 10,120 mg, sodium lauryl sulfate 2,300 mg, sodium carboxymethyl starch 18,400 mg, magnesium stearate 0.690 mg, povidone 11,500 mg, talc 0.460 mg, microcrystalline cellulose 36.530 mg.

Shell:

opada white Y-1-7000 5,000 mg (hypromellose 5cP 3.125 mg, titanium dioxide E171 1.5625 mg, macrogol-400 0.3125 mg).

Description:

Round biconvex tablets, covered with a film coating of white color with a risk on one side. The core is white.

Pharmacotherapeutic group:antiarrhythmic drug

Pharmacodynamics:

Propafenone is an antiarrhythmic drug that possesses membrane-stabilizing properties, properties of a blocker of sodium channels (class IC) and poorly expressed beta-adrenergic blocking activity (class II).

Local anesthetic effect approximately corresponds to the activity of procaine. Reduces the maximum depolarization rate of phase 0 of the action potential and its amplitude in Purkinje fibers and contractile fibers of the ventricles, inhibits automatism. Slows down the Purkinje fibers. Extends the timing of the sinoatrial (SA) node and atria. Does not affect or slightly increases the corrected recovery time of the sinus node function with programmable electrical stimulation.

Increases the effective refractory period of the atrioventricular node, inhibits the conduct of additional paths in the retrograde and antegrade directions, increases the threshold of stimulation of the ventricles.

Electrophysiological effects are more pronounced in ischemic than in normal myocardium. Has a negative inotropic effect, which usually manifests itself when the left ventricular ejection fraction is lower than 40%. Action begins 1 hour after ingestion and persists for 8-12 hours.

Pharmacokinetics:

Absorption

More than 95% of the drug is absorbed. Systemic bioavailability is 5-50%. Admission with food increases bioavailability in patients with intensive metabolism.

Propaphenone exhibits dose-dependent bioavailability, which increases non-linearly with increasing dose: it increases from 5% to 12% with a single dose increase from 150 mg to 300 mg, and at 450 mg to 40-50%. Time to reach the maximum concentration in the blood plasma (TC_mOh) after oral administration is 1-3.5 h and its value varies from 500 to 1500 mcg / l. The equilibrium concentration (Css) in the blood plasma is achieved 3-4 days after the start of therapy.

Distribution

Permeability through the blood-brain and placental barrier is low. The concentration of propafenone in the umbilical cord is 30% of its concentration in the mother's blood. The volume of distribution is 3-4 l / kg.

Connection with proteins of blood plasma and internal organs (liver, lungs, etc.) - 85-97%. Propafenone is subjected to a significant and saturated presystem biotransformation by isoenzyme CYP2D6 (the effect of "primary transmission" through the liver), which leads to absolute bioavailability, dose-dependent and dosage form of the drug.

Metabolism

There are 2 models of genetically determined metabolism of propafenone. More than 90% of patients propafenone rapidly and significantly metabolized, half-life (T_1/2) is from 2.8 to 11 hours.

11 metabolites of propafenone are described, of which two are pharmacologically active: 5-hydroxypropaphenone is formed by isoenzyme CYP2D6, and N-dropropylpropaphenone (norpropaphenone) - with the help of isoenzymes CYP3A4 and CYP1A2. Less than 10% of patients propafenone is metabolized more slowly, since 5-hydroxypropaphenone is not formed or is formed in small amounts. In this type of metabolism, the half-life is about 17 hours. With a significant metabolism with a cycle of saturated hydroxylation with the aid of an isoenzyme CYP2D6 pharmacokinetics of propafenone is nonlinear, and for slow metabolism it is linear. Since the equilibrium state of pharmacokinetic parameters is achieved 3-4 days after oral administration of the drug in all patients, the dosage regimen of the drug is the same for all patients regardless of metabolic rate. Pharmacokinetics has a significant individual variability, which is mainly due to the effect of "primary transmission" through the liver, as well as its non-linearity in extensive metabolism. The variability of the concentration of propafenone in the blood requires careful titration of the dose and monitoring of patients, including ECG monitoring.

Excretion

It is excreted by the kidneys - 38% in the form of metabolites (less than 1% unchanged), through the intestines with bile - 53% (in the form of glucuronides and sulfates of metabolites and unaltered propafenone.With hepatic failure, excretion decreases.

Indications:

Prevention and treatment of ventricular arrhythmias;

Prevention and treatment of paroxysmal supraventricular tachyarrhythmias (including atrial fibrillation / flutter, paroxysmal supraventricular tachycardia of the type re-entry with the involvement of the atrioventricular node or additional ways of carrying out when another therapy is ineffective or contraindicated).

Contraindications:

If you have any of the listed diseases, before taking the drug, be sure to consult a doctor.

- Hypersensitivity to propafenone and components of the drug;

- tsevere forms of chronic heart failure (in the stage of decompensation), uncontrolled chronic heart failure;

- toardiogenic shock (with the exception of arterial hypotension due to tachycardia and antiarrhythmic shock);

- tsevere bradycardia and arterial hypotension;

- fromInoatrial blockade, atrial atrial fibrillation;

- bfovea of the arms of the bundle or distal blockade (in patients without an electrocardiostimulator);

- atSevere disturbances of the water-electrolyte balance (eg, disturbances in potassium metabolism),

- mIastension;

- tsevere forms of chronic obstructive pulmonary disease (COPD), bronchospasm (in the anamnesis);

- atnutric ventricular bifascicular block and atrioventricular block II-III degree (without pacemaker);

- fromthe weakness of the sinus node;

- fromindra "tachycardia-bradycardia";

- atSevere organic changes in the myocardium, such as refractory chronic heart failure with a left ventricular ejection fraction of less than 35% and cardiogenic shock, with the exception of arrhythmic shock;

- aboutsimultaneous application of ritonavir in a dose of 800-1200 mg / day;

- Ppatients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption;

- atozrast to 18 years (efficiency and safety not established).

Carefully:

If you have any of these diseases, consult a doctor before taking the drug.

Myasthenia gravis gravis, impaired renal and / or liver function, COPD (with extreme caution due to beta-adrenergic blocking action), advanced age,patients with an established artificial heart rhythm driver, violations of water-electrolyte balance, arterial hypotension, simultaneous use with other antiarrhythmic drugs.

Pregnancy and lactation:

The use of propafenone during pregnancy, especially in the first trimester, is only possible if the expected benefit to the mother exceeds the potential risk to the fetus. Propafenone penetrates the placental barrier. The concentration of propafenone in the umbilical cord is 30% of its concentration in the mother's blood.

Propaphenone is excreted in breast milk. If it is necessary to use the drug propafenone During lactation breastfeeding should be discontinued.

Dosing and Administration:

Inside. Tablets should be swallowed whole, after eating, with a small amount of water.

The dosage regimen is set individually and adjusted by the doctor. It is recommended to begin therapy in a hospital, previously abolishing all antiarrhythmic drugs (under the control of blood pressure, ECG, assessing the latitude of the complex QRS).

In patients with a significantly expanded complex QRS and AV blockade II and III degree is recommended to reduce the dose.

With a body weight of 70 kg or more, the initial dose is 150 mg 3 times a day (in a hospital under the control of blood pressure, ECG). The dose can be increased gradually, at intervals of 3-4 days to 300 mg 2 times a day, and if necessary up to a maximum dose of 300 mg 3 times a day.

In elderly patients, patients with a body weight of less than 70 kg, the drug is started with lower doses, gradually increasing the dose. The same tactics should be followed when carrying out maintenance therapy. Do not start increasing the dose if the duration of the drug is less than 5-8 days.

When liver function is impaired (cumulation possible) Propafenone is used in the doses that make up 20-30% of the usual, with a violation of kidney function (creatinine clearance less than 10%), the initial dose is 50% of the usual.

Side effects:

From the hematopoiesis: leukopenia, granulocytopenia, thrombocytopenia, agranulocytosis, increased bleeding time, manifestation of antinuclear antibodies; From the immune system: allergic reactions, hypersensitivity reactions (manifested by cholestasis, pathological changes in the blood).

From the side of metabolism: decreased appetite.

From the nervous system: headache, dizziness, fainting, impaired coordination of movements, anxiety, anxiety, confusion; nightmares, sleep disorders, extrapyramidal symptoms, vertigo, paresthesia, convulsions.

From the side of the organ of vision: blurred vision, diplopia.

From the side of the cardiovascular system: pronounced bradycardia, atrioventricular dissociation, ventricular tachyarrhythmias, angina pectoris, worsening of the course of heart failure (in patients with reduced left ventricular function), conduction disorders (sinoatrial block, atrioventricular block, intraventricular blockade), proarrhythmic effect (tachycardia, ventricular fibrillation), supraventricular tachyarrhythmias, high doses - a marked decrease in blood pressure, including postural and orthostatic hypotension (especially in elderly patients), chest pain.

From the side of the digestive system: nausea, vomiting, constipation, dryness of the oral mucosa, bitter taste in the mouth, abdominal pain, diarrhea, flatulence, belching, taste change; violations of the liver, including hepatocellular disorders, cholestatic jaundice, cholestasis, hepatitis.

From the skin: lupus-like syndrome, reddening of the skin, skin rash, itching, exanthema, urticaria, hemorrhagic rashes on the skin.

From the genitourinary system: oligospermia, decreased potency.

Other: weakness, increased sweating, bronchospasm.

Laboratory indicators: increased activity of "liver" transaminases.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Intoxication can occur with a single-dose dose, 2 times the daily dose; symptoms of intoxication appear after 1 hour, maximum - after several hours.

Overdose Symptoms: persistent reduction in blood pressure, nausea, dry mouth, vomiting, mydriasis, drowsiness, extrapyramidal disorders, confusion, bradycardia, lengthening of the interval Q-T atrial and intraventricular conduction abnormalities, ventricular tachyarrhythmias, paroxysms of polymorphic ventricular tachycardia, sinoatrial and atrioventricular blockades, asystole, coma, convulsions, delirium, pulmonary edema.

Treatment: gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary - artificial ventilation and indirect heart massage. Because the propafenone has a large volume of distribution and a high degree of binding to plasma proteins (more than 95%), then hemodialysis and hemoperfusion are not effective.

Interaction:

Pharmacodynamic interaction

With the intravenous administration of lidocaine simultaneously with propafenone - an increased risk of damage to the central nervous system.

With simultaneous use with beta-blockers, it is possible to intensify antiarrhythmic action, with local anesthetics and drugs that inhibit cardiac activity-enhancing the effect of propafenone. With the simultaneous use of propafenone with misolastine, ritonavir, tricyclic antidepressants or antipsychotics, the risk of arrhythmia increases.

The use of propafenone in combination with phenobarbital and / or rifampicin can reduce the antiarrhythmic efficacy of propaphenone hydrochloride.

Amiodarone increases the risk of developing tachycardia such as pirouette.It may be necessary to adjust the doses of both drugs depending on the therapeutic response. Drugs that depress the sinoatrial and atrioventricular nodes and have a negative inotropic effect, increase the risk of side effects. Drugs that inhibit bone marrow hematopoies increase the risk of myelosuppression.

Pharmacokinetic interaction

Increases the concentration in the blood plasma of propranolol, metoprolol, digoxin (the risk of developing glycoside intoxication), anticoagulants of indirect action, cyclosporine, theophylline, desipramine. Strengthens the effect of warfarin (blocks metabolism).

Cimetidine, quinidine, ketoconazole, tropospheric, dolasetron, misolastine, erythromycin and grapefruit juice, slowing metabolism, increase the concentration of propafenone in the plasma by 20%, so patients should be carefully monitored and accordingly adjusted the dose of propafenone, rifampicin - reduces.

The use of propafenone hydrochloride in combination with venflaxin can lead to an increase in the concentration of venflaxin. With the simultaneous use of propafenone hydrochloride and fluoxetine in "fast" metabolizersincreases C_max S-propachenone by 39% and AUC by 50%, and C_mOh R-propacenone by 71% and AUC on 50%. Therefore, lower doses of propafenone may be sufficient to achieve the desired therapeutic response.

An increase in the level of propafenone in plasma can occur with simultaneous application with paroxetine, therefore, the dose of propafenone should be reduced.

The simultaneous use of propafenone hydrochloride and ritonavir in a dose of 800-1200 mg / day is contraindicated in connection with a potential increase in the concentration in the blood plasma.

Special instructions:

During the course of treatment, especially at the beginning of therapy, ECG monitoring is necessary. Treatment is recommended to begin in a hospital, because the risk of arrhythmogenic action associated with the use of propaphenone is increased.

Application Propafenone should be administered under the control of electrolyte blood balance (especially potassium content) and ECG. In the case of changes in the ECG, for example, the expansion of the complex QRS or lengthening the interval Q-T more than 25% or PR interval of more than 50% or interval Q-T more than 500 msec or an increase in the frequency and severity of cardiac arrhythmias, it is necessary to decide whether to continue treatment.

In elderly patients or patients with significant impairment of left ventricular function (LV ejection fraction <35%) or with organic myocardial changes, treatment should be started gradually, with extreme caution, and the dose should be increased gradually. The same applies to maintenance therapy. Any increase in the dose that may be required should be made after 5-8 days of treatment.

In elderly patients or patients with organic myocardial changes, the dose of the drug should be titrated with great care. In the treatment of paroxysmal atrial fibrillation, there may be a transition from atrial fibrillation to atrial flutter to 2: 1 or 1: 1 ventricles, with a very high ventricular contraction rate (ie> 180 beats per minute).

Treatment with the drug may affect the sensitivity threshold and the frequency threshold of artificial pacemakers. Therefore, pacemakers need to be checked and, if necessary, reprogrammed, as the drug can affect the sensitivity threshold and the frequency threshold of the artificial pacemaker. Periodically, the activity of "liver" transaminases should be determined.

When treating ventricular arrhythmias Propafenone more effective antiarrhythmic drugs IA and IB classes.

In patients with liver function deficiency, the bioavailability of Propaphenone increases by 70%, in such patients it is recommended to lower the dose and conduct regular monitoring of laboratory parameters.

Indications and dosage should be carefully determined for patients with an artificial pacemaker.

Patients undergoing long-term treatment with anticoagulants and hypoglycemic drugs, it is necessary to conduct careful clinical as well as laboratory monitoring.

In the event that during the therapy there is a sinoatrial block or atrioventricular blockade of the third degree, or a recurring extrasystole, the treatment should be stopped.

Given the likely proaritmogenic effect on the prognosis of the patient's condition, the drug is recommended to be used only for the intended purpose and under the supervision of the doctor.

The drug contains lactose monohydrate. It should be taken into account in patients with lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

Features of the drug during its cancellation

Despite the absence of a "cancellation" syndrome in BCCA (a blocker of slow calcium channels), a gradual decrease in doses is recommended before cessation of treatment.

Features of the actions of the doctor (paramedic), the patient with a missed intake of one or more doses of the drug

It is necessary to take the missed dose as soon as an omission is discovered. If it is time to take the next dose, you need to skip the missed and continue to receive the prescribed schedule. Do not take a double dose to compensate for the missed dose.

Effect on the ability to drive transp. cf. and fur:

During the treatment period, it is necessary to refrain from managing vehicles, mechanisms and occupations of potentially hazardous activities requiring increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:Tablets coated with a coating, 150 mg.

Packaging:

10 tablets per blister are perforated from aluminum foil and PVC film.

4 blisters (40 tablets) or 5 blisters (50 tablets) together with instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000622

Date of registration:07.07.2010

The owner of the registration certificate:Alkaloid, JSCAlkaloid, JSC Macedonia

Manufacturer: & nbsp

ALKALOID, AD Macedonia

Representation: & nbspALKALOID, AOALKALOID, AO

Information update date: & nbsp04.09.2015

Illustrated instructions

Instructions

Propafenone (Propafenone)