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

Active substancePropafenonePropafenone

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Dosage form: & nbspsolution for intravenous administration

Composition:

One ampoule with 10 ml of solution for intravenous administration contains:

active substance: propafenone hydrochloride 35,000 mg;

Excipients: dextrose monohydrate 250,000 mg, propylene glycol 100,000 mg, hydrochloric acid 0.001 mg, water for injection up to 10,000 ml.

Description:

A clear, colorless solution.

Pharmacotherapeutic group:antiarrhythmic drug

ATX: & nbsp

C.01.B.C Antiarrhythmic drugs Ic class

C.01.B.C.03 Propafenone

Pharmacodynamics:

Propafenone is an antiarrhythmic drug with membrane-stabilizing properties, sodium channel blocker properties (class IC) and poorly expressed beta-adrenoblocking 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%.

Pharmacokinetics:Absorption

More than 95% of the drug is absorbed. Propafenone exhibits a dose-dependent bioavailability, which increases non-linearly with increasing dose.

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%.

Propaphenone is subjected to a significant and saturate 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- depropylpropaphenone (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 taking the medication internally in all patients,then the dosage regimen of the drug is the same for all patients regardless of the 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 dose titration 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 intestine with bile - 53% (in the form of glucuronides and sulfates of metabolites and unaltered propafenone). With hepatic failure, excretion decreases.

Indications:

- Supraclavicular and ventricular extrasystole;

- paroxysmal rhythm disturbances (supraventricular - atrial fibrillation and flutter, Wolff-Parkinson-White syndrome);

- atrioventricular re-entry tachycardia;

- stable monomorphic ventricular tachycardia.

Contraindications:

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

- Hypersensitivity to propafenone and components of the drug;

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

- cardiogenic shock (except arterial hypotension due to tachycardia and antiarrhythmic shock);

- severe bradycardia and arterial hypotension (systolic blood pressure less than 90 mm Hg);

- sinoatrialnaya blockade, violations of atrial atrial conductivity;

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

- pronounced disturbances of water-electrolyte balance (for example, disturbances of potassium metabolism);

- myasthenia gravis;

- intraventricular bifascycle blockade and AV blockade II-III degree (without pacemaker);

- syndrome of weakness of the sinus node;

- syndrome of "tachycardia-bradycardia";

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

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

- syndrome of glucose-galactose malabsorption;

- age to 18 years (efficacy 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, chronic obstructive pulmonary disease (COPD) (with extreme caution due to beta-adrenergic blocking action), elderly age, patients with an established pacemaker, impaired water-electrolyte balance, arterial hypotension, simultaneous application with other antiarrhythmic agents.

Pregnancy and lactation:

The use of propaphenone 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:

Intravenously.

The dosage regimen is set individually and adjusted by the doctor.

The daily dose is 560 mg. 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 elderly patients, patients with a body weight of less than 70 kg, the drug is started with lower doses, gradually increasing the dose.

A dose of 0.5-1 mg / kg body weight is administered intravenously slowly for 3-5 minutes. If necessary, this dose can be re-entered after 90-120 minutes.

In severe arrhythmia, short-term or prolonged infusions of Proparanone in a 5% solution of dextrose (glucose) or in a solution of fructose (levulose) are used.

Continuous infusion is administered intravenously drip 3-5 min after intravenous administration.

If on the background of treatment there is an expansion of the complex QRS or interval Q-T more than 20% in comparison with the initial values, or an extension of the interval P-Q more than 50%, lengthening interval Q-T more than 500 msec, an increase in the frequency and severity of arrhythmia, the dose should be reduced, or the use of propa- phenone should be temporarily discontinued.

Do not mix with 0.9% solution of sodium chloride.

Side effects:

On the part of the hematopoiesis system: 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, restlessness, confusion, sleep disturbances, nightmares, extrapyramidal symptoms, vertigo, paresthesia, convulsions.

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

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

On the part of the digestive system: nausea, vomiting, constipation, dryness of the oral mucosa, bitter taste in the mouth, abdominal pain, diarrhea, eructation, flatulence, taste change, liver function abnormalities, including hepatocellular disorders, cholestatic jaundice, cholestasis, hepatitis.

From the skin: lupus-like syndrome, reddening of the skin, skin rash, itching, exanthema, urticaria, haemorrhagic 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 indicated in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor about it.

Overdose:

Symptoms of overdose: persistent lowering of arterial pressure, nausea, dryness of the oral mucosa, 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.

Giving help: defibrillation, administration of dobutamine, diazepam; if necessary - artificial ventilation and indirect heart massage. Hemodialysis is 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, which inhibit cardiac activity, intensifying 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" metabolizers increases 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 at a dose of 800-1200 mg / day is contraindicated in connection with a potential increase in plasma concentration.

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. The use of propaphenone should be carried out 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 the case of elderly patients or patients with significant impairment of left ventricular function or with organic myocardial damage, treatment should be started gradually, with special care and dose increment 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 insufficient liver function, the bioavailability of propafenone increases by 70%, in such patients it is recommended to reduce the dose and to conduct regular monitoring of laboratory parameters.

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

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

If during the therapy SA blockade or AV blockade of the third degree, or a frequently recurring extrasystole, then treatment should be stopped.

The drug contains dextrose monohydrate. It should be taken into account in patients with glucose-galactose malabsorption syndrome.

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

Studies to assess the impact on the ability to drive vehicles, mechanisms have not been carried out.

Form release / dosage:

Solution for intravenous administration, 3.5 mg / ml.

Packaging:

For 10 ml of the drug in colorless glass ampoules.

5 ampoules are packed in a contour mesh package.

2 contour squares (10 ampoules), 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-000623

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: & nbsp05.09.2015

Illustrated instructions

Instructions

Propafenone (Propafenone)