Propanorm, 150 mg 50 pcs.

Propanorm is an antiarrhythmic.

Pharmacodynamics

The IC class antiarrhythmic drug, blocks fast sodium channels. It has weak beta-adrenoblocking activity and m-cholinoblocking action. Antiarrhythmic effect is based on local anesthetic and direct membrane stabilizing effect on myocardiocytes as well as on blockade of beta-adrenoreceptors and calcium channels.

Causes dose-dependent decrease in depolarization rate, inhibits phase 0 action potential and its amplitude in Purkinje fibers and ventricular contractile fibers, inhibits automatism. Delays conduction along Purkinje fibers. It prolongs conduction time through the sinoatrial (SA) node and atria. When propafenone is used, the PQ interval is prolonged and the QRS complex is widened (15 to 25), as well as the AH and HV intervals. The drug prolongs the effective refractory period in the atria, AV node, accessory bundles and, to a lesser extent, in the ventricles. No significant changes in the QT interval are observed. Electrophysiological effects are more pronounced in ischemic than in normal myocardium. It has a negative inotropic effect, which is usually manifested when left ventricular ejection fraction decreases below 40%.

The action begins 1 h after oral administration, reaches a maximum after 2-3 h and lasts 8-12 h.

Pharmacokinetics

The absorption of more than 95% of the drug. Propafenone exhibits dose-dependent bioavailability, which increases nonlinearly with increasing dose: it increases from 5% to 12% when the single dose is increased from 150 to 300 mg, and from 450 mg to 40-50%. C_max in plasma after oral administration is reached within 1-3.5 h and ranges from 500 to 1500 µg/L. The permeability through the HEB and the placental barrier is low. The volume of distribution is 3-4 l/kg. Binding with plasma proteins and internal organs (liver, lungs, etc.) is 85-97%.

Therapeutic range of propafenone concentration in blood plasma is 0.5-2.0 mg/l. Propafenone is almost completely metabolized. Eleven metabolites of the drug have been described – 5-hydoxypropafenone and N-depropylpropafenone are pharmacologically active, having antiarrhythmic activity comparable to propafenone. T_1/2 “fast metabolizers” is 2-10 h, “slow” – 10-32 h, biologicalT_1/2 is about 6.2 h. Excretion: by kidneys – 38% as metabolites (less than 1% unchanged), in the bile – 53% (as glucuronides and sulfates). In hepatic insufficiency the excretion decreases.

Indications

Prevention and treatment of supraventricular and ventricular extrasystoles, paroxysmal rhythm disturbances (supraventricular – atrial fibrillation and flutter, WPW-syndrome), atrial-ventricular re-entry tachycardia;

Prevention of sustained monomorphic ventricular tachycardia.

Active ingredient

Composition

Active ingredient:

Propafenone hydrochloride 150 mg;

Associates:

Microcrystalline granulated cellulose,

Corn starch,

copovidone,

sodium croscarmellose,

magnesium stearate,

sodium lauryl sulfate,

hypromellose 5,

p> macrogol 6000,

titanium dioxide,

emulsion of dimethicone with silicon dioxide.

How to take, the dosage

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

The drug is taken after a meal. The tablets should be swallowed whole, without chewing, with a small amount of water.

The drug is given as 150 mg 3 times a day (every 8 hours). The daily dose is 450 mg.

The dose is increased gradually (every 3 to 4 days) to 600 mg/day (divided into 2 doses) or to a maximum of 900 mg/day (divided into 3 doses).

If during treatment, extension of QRS complex or QT interval by more than 20% compared to baseline values, or prolongation of PQ interval by more than 50%, prolongation of QT interval by more than 500 msec, increase in arrhythmia frequency and severity, the dose should be reduced or Propanorm should be temporarily stopped.

Propanorm use in hepatic dysfunction: If liver function is impaired (cumulation is possible), Propanorm is used in doses that are 20-30% of the usual dose.

Application in renal dysfunction: In renal dysfunction (creatinine clearance < 10 ml/min) the initial dose is 50% of the initial dose.

Application in elderly patients and patients with a body weight less than 70 kg: In patients over 70 years of age as well as in patients with a body weight of < 70 kg a smaller dose is used (the first dose is given in the hospital under control of ECG and BP).

Interaction

Propanorm should not be combined with lidocaine because the cardiodepressant effect is increased.

In concomitant use propafenone increases plasma concentrations of propranololol, metoprolol, digoxin (increased risk of glycoside intoxication), indirect anticoagulants, cyclosporine.

In concomitant use propafenone increases the effect of warfarin (by blocking the metabolism).

Concomitant use with beta-adrenoblockers, tricyclic antidepressants and may increase the antiarrhythmic effect.

Concomitant use with local anesthetics increases the risk of CNS damage.

Cimetidine and quinidine, by slowing down the metabolism, increase the plasma concentration of propafenone by 20%, rifampicin decreases it.

In concomitant use with propafenone, amiodarone increases the risk of pirouette tachycardia.

The drugs depressing sinoatrial node and AV node and having negative inotropic effect increase the risk of side effects when used concomitantly with propafenone.

Drugs that inhibit medullary hematopoiesis increase the risk of myelosuppression when used concomitantly with propafenone.

Special Instructions

In the course of treatment, especially at the beginning of therapy, ECG monitoring is necessary.

The treatment is recommended to start in a hospital setting because of the increased risk of arrhythmogenic effects associated with the use of propafenone.

Propanorm should be used under monitoring of blood electrolyte balance (especially potassium concentration) and ECG; hepatic transaminase activity should be determined periodically.

In the treatment of ventricular arrhythmias, propafenone is more effective than Class IA and IB antiarrhythmic drugs.

The indication and dose should be particularly carefully determined for patients with a pacemaker.

Clinical and laboratory monitoring should be performed in patients undergoing long-term treatment with anticoagulants and hypoglycemic agents when Propanorm is used concomitantly.

If sinoatrial blockade or AV blockade of degree III, or recurrent extrasystole are noted during treatment, treatment must be discontinued.

Contraindications

Side effects

Cardiovascular system disorders: bradycardia, AV dissociation, ventricular tachyarrhythmias, angina pectoris, worsening of heart failure (in patients with reduced left ventricular function), sinoatrial blockade, AV blockade, intraventricular conduction disorders, supraventricular tachyarrhythmias, in high doses – orthostatic hypotension.

Digestive system disorders: change in taste, dry mouth, bitter mouth, nausea, decreased appetite, feeling of heaviness in epigastrium, constipation or diarrhea; rarely – liver function disorders, cholestatic jaundice, cholestasis.

CNS disorders: headache, dizziness; rarely – blurred vision, diplopia, seizures.

Hematopoietic system disorders: leukopenia, agranulocytosis, increased bleeding time, thrombocytopenia, appearance of antinuclear antibodies.

In the sexual system: oligospermia, decreased potency.

Allergic reactions: skin rash, itching, exanthema, skin redness, urticaria, lupus-like syndrome.

Others: weakness, bronchospasm, hemorrhagic rashes on the skin.

Overdose

If a single dose of twice the daily dose is taken, symptoms of intoxication may appear in 1 hour, maximum in a few hours.

Symptoms: Persistent BP decrease, nausea, dry mouth, vomiting, mydriasis, somnolence, extrapyramidal disorders, confusion, bradycardia, QT interval prolongation, intraatrial and intraventricular conduction disorders, ventricular tachyarrhythmias, polymorphic ventricular tachycardia paroxysms, sinoatrial block, AV blockade, asystole, coma, seizures, delirium, pulmonary edema.

Treatment: gastric lavage, defibrillation, administration of dobutamine, diazepam; if necessary – EVL and indirect heart massage. Hemodialysis is ineffective.

Pregnancy use

The use of propafenone in pregnancy, especially in the first trimester, is possible only when the expected benefit to the mother exceeds the potential risk to the fetus.